proceedings from the international radiopharmaceutical...

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Proceedings from the International Radiopharmaceutical Education Consortium Workshop

Bühl, Germany, 20-22 July 2000

Senior Guest Editor: H.J. Machulla, Eberhard-Karls Universität, Tübingen, Germany

Guest Editors: LI Wiebe, JR Mercer and SA McQuarrie, University of Alberta, Alberta, Canada

This supplementary issue of JPPS presents the deliberations of an international group of radiopharmaceutical scientists with academic, clinical and industrial backgrounds. Their common goal was to provide a philosophical basis from which a distance-learning template could be implemented. The end product of this exercise would be a multi-institutional distance-based didactic resource in the radiophar-maceutical sciences. This material would include both virtual classroom and laboratory settings in which the students could gain exper-tise in the practice of radiopharmacy. This computer database would also be designed to maximize the use of other resources available on the Internet. The magnitude of this project is such that an international expert collaboration is necessary in order to complete it in a timely, comprehensive and cost-effective way.

Acknowledgements

We wish to thank the 21 delegates from 7 countrieswho attended the Workshop. Technical support wasprovided by scientific and technical members of theTübingen PET Centre, and secretarial support wasprovided by Ms. Conny Daiker and Mr. Hans JörgRahm. We would also like to thank the management ofthe Hotel Germania in Bühl for their warm hospitality.

Delegates

Hans-Jürgen Machulla (Germany); Georg Becker(Germany); Clyde Cole (United States); Peter Cox(Netherlands); Kara Duncan (United States); Peter Eu(Australia); Daniela Gündisch (Germany); AkliHammadi (France); Bernd Johannsen (Germany);David Laven (United States); Steve J Mather (UnitedKingdom); Steve A McQuarrie (Canada); John Mercer,(Canada); Hans Jörg Rahm (Germany); Gerald Reischl(Germany); Frank Rösch (Germany); Stan Shaw(United States); Gerrit Westera (Switzerland); LeonardWiebe Canada); Wolfgang Wiegrebe (Germany).

PrefaceH-Jürgen Machulla and Leonard I. Wiebe

The concept of developing computer-based resourcesto support didactic teaching of the radiopharmaceuticalsciences outlined in this document originated from dis-cussions among Prof. Peter Cox (Daniel den HoedClinic, Netherlands), Prof. Stan Shaw (Purdue U.,USA) and Prof. Len Wiebe (U. Alberta, Canada) dur-ing recent international symposia1. Prof. Shaw visited

the University of Alberta in September, 1998, toexplore methods of adapting and updating Purdue'snuclear pharmacy ‘video-tape course material’. TheAlberta group (Drs. McQuarrie, Mercer and Wiebe)consequently pursued the development of 'Web-based'tools in late 1998, focusing on presentation through ateaching platform called WebCT™. In 1999, Mr. PeterEu (Peter MacCallum Cancer Institute, Australia) andProf. Jürgen Machulla (U. Tübingen, Germany) joinedthis initiative, and by mid-1999, McQuarrie and Mer-cer had up-loaded a substantial amount of course mate-rial onto the WebCT™ platform2, including a virtuallaboratory exercise3 developed using Authorware (ver-sion 4, Macromedia Inc.).

At the time the Workshop was beginning to takeshape, several independent international initiatives todevelop Web- and/or CD-ROM - based course materi-als for teaching radiopharmacy and radiopharmaceuti-cal chemistry were being planned or actively pursuedby other groups. Discussions4 among Cox, Machullaand Wiebe focused on pulling together an internationalworking group to develop a comprehensive teaching‘database’.

1 Int. Symp. on Modern Trends in Radiopharmaceuticals for Diagnosis andTherapy. IAEA Symp. Lisbon, Portugal, Mar 1998; 9th Europ. Symp.Radiopharm. Radiopharmaceuticals, Lillehammer, Norway Mar 1999.2 J.R. Mercer and S.A. McQuarrie: Basic nuclear concepts, used in Pharmacy443 (undergraduate course in radiopharmacy) and Pharmacy 601 (graduatecourse in tracer methodology).3 S.A. McQuarrie and J. R. Mercer: A Virtual GM Lab – Part 1: Half-lifeDermination.4 Eberhard-Karls Universität, Tübingen, Germany, 16 February 2000.

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It was envisaged that materials to be included in theproposed database would eventually cover the fullgamut of radiopharmaceutical sciences and selectedclinical nuclear medicine materials, using didactic textwith interactive graphics (including demonstrationvideo clips), virtual interactive experiments, self-administered learning evaluation and testing capability,and on-line or e-mail access to international teachingfaculty. Furthermore, although this material would initself not constitute a formal course for practice licens-ing, it would be comprised of units which an instructorcould ‘bundle’ to meet a given set of criteria. Each unitwould contain didactic material presented in a stan-dardized manner and on a common platform, utilizingeither the Web and/or CD-ROM. Bundled databaseunits would be accessible to subscribers (instructors,students, Institutions) on a license or user fee-basis,much as electronic textbooks are available on the Webtoday.

Initial objectives of the Workshop were to:• develop a consensus for database content and associ-

ated publications,• integrate available resources already developed by

stakeholders, and• assign responsibilities for the development or refine-

ment of major subject-content units to Workshopdelegates, based on their resources, enthusiasm andability to provide materials within a specified time-frame.

The Workshop's opening 'working paper' (McQuarrie,Mercer and Wiebe) served as a basis upon which todevelop the rationale and program for the 'Radiophar-maceutical Sciences Database Workshop'. Approxi-mately 20 educator-scientists were invited to participatein the Workshop, ensuring broad subject coverage andregional input, yet limiting the group size so that pro-ductivity would be emphasized. The format chosen toachieve these goals included a review of the objectivesof the exercise, and superficial examination of databasecontent. Presentations of ‘works in progress’ by Work-shop participants, followed by a break-out session todevelop themes (theme groups), preceded the establish-ment of working interest groups (management, tech-nology and content). Reports from each of theseinterest groups provided the basis for construction of atimetable for ‘deliverables’, and the identification ofdates and venue(s) for future meetings.

1 INTRODUCTION: COMPUTER-BASED RESOURCES FOR THE RADIOPHARMACEUTICAL SCIENCES

Leonard I. Wiebe

This Workshop was convened by Professor Machulla,Tübingen University, with the encouragement andsupport of several members of the international radiop-harmaceutical sciences community. The objectives are1) to determine the level of support from within thecommunity to develop a modern, computer-basedknowledge base for both training and upgrading per-sonnel engaged professionally in the field of radiophar-maceutical sciences, and 2) to establish working groupsto develop issues of management, content and selectionof electronic medium. These important questions mustbe addressed in order to rationalize a concerted, multi-national approach to this challenge.

The first question is ‘why?’. There are several reasonsto consider a computer-based data resource, includingconvenience and accessibility for both the educator andthe student. In addition, computer material can bereadily ‘layered’ to provide stepwise grading from thesimple presentation of a subject, through to the mostadvanced level. This material can also be presented indynamic fashion, not only creating interest for the stu-dent, but enabling the student to undertake a numberof ‘virtual’ exercises such as the ‘G-M lab’ that has beendeveloped by Drs. Mercer and McQuarrie (U. Alberta).Additionally, the tasks of editing and upgrading forboth accuracy and currency are facile, compared tosuch changes to a hard-copy document. Finally, byworking as a group, participants in the program wouldbenefit from each others contributions and at the sametime ensure that the materials would meet their ownexacting standards of quality and detail.

Who would be the target audience? This material couldbe presented in a modular fashion with respect to bothsubject material and depth of knowledge within eachsubject module. As such, the material would be usefulfor not only radiopharmacists and radiochemists, butalso for technical staff and medical staff. Furthermore,material could be selected from this modular databaseto meet the didactic needs for any interest group, be itan academic user preparing a ‘credit’ course’ in a Uni-versity or Technical School, or a professional /regula-tory body offering courses for (practice) licensure.

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What resources would be required? Clearly, the intel-lectual resources necessary to create a base of material(content) and a storage/distribution modality (plat-form) already lie within the assembled group, or areavailable for recruitment as deemed necessary. Ques-tions such as internet versus CD-ROM, server site loca-tions, access to programs (pass-word/license), and thedevelopment of teaching utilities (e.g. WebCT™ grad-ing/record keeping/student chat rooms, etc.) associatedwith modules of the database, would need to be clari-fied.

How could this be achieved? The first step would be toestablish a management structure to ensure orderlyprogression towards clearly identified goals. As an ini-tial proposal, members of the Workshop could chose tojoin management, content or platform groups, to estab-lish a temporary framework through which detailedtasks were to be identified and executed. Internal focus,together with adequate information exchange amongthese working groups allowed a plan to be developed,even within the short period that this Workshop wasin session.

What are the Workshop deliverables? The establish-ment of a management structure, followed by initialdiscussions on organization, content and platformwould form the basis for a Planning Guide for the Devel-opment of Computer-based Resources for (teaching in) theRadiopharmaceutical Sciences. It would seem appropri-ate for this Guide to be produced either in hard copy orin an accessible Internet file.

2 PRELIMINARY WORKSHOP AGENDA

General themes (Chair: L. I. Wiebe)

• Η-J Machulla (Germany) and L. I. Wiebe (Canada):Statement of Workshop objectives and philosophy.

• S. Mather (UK): International market; issues of lan-guages and national jurisdictions.

• D. Laven (USA): Target groups, including pharma-cists, radiochemists, research support staff, technicalsupport staff and others.

• S. Shaw (USA): Users of didactic database materials- undergraduate and postgraduate (degree) programsin universities, professional societies (post-degreecertification), government regulatory/licensing bod-ies (post-degree certification), and industry.

• C. Coles (USA): Joint venture issues - ownership &copyright, rights to utilization, cost to users.

• P. Cox (Netherlands): Target venues, including Uni-versity degree credit, University certification andcertification by societies and government authori-ties.

• S. McQuarrie (Canada): Web-based Platforms -Java/C+, WebCT and others.

Current status of training programs (Chair: J. Mercer)• S. McQuarrie and J. Mercer - Canada• P. Eu - Australasia• S. Mather (UK) and G. Westera (Switzerland) -

Europe• S. Shaw and K. Duncan - USA

Breakout interest groups Three groups were organized, with membership bypersonal preference.1. Scope and content of course materials (Secretary: J.

Mercer). This group addressed definition of goals,assigning responsibilities for topics, graphics andpublications, reviewing and editing, regional spe-cialization and translations.

2. Media / platforms / software / hard copy (Secre-tary: S. Mather).

3. Identifying and contacting the audience, definingthe scientific and industry stakeholders (Secretary:C. Coles).

3 CURRENT PROGRAMS AND STATUS

3.1 A European Post-Graduate Specialisation In Radiopharmacy

Stephen J Mather, Imperial Cancer Research Fund, Dept.Nuclear Medicine, St. Bartholomew's Hospital, London,Great Britain• The EANM Radiopharmacy Committee has been

working towards the establishment of a Europe-wide qualification in Radiopharmacy to help:1.set and maintain standards in the radiopharmaceu-

tical sciences,2.provide a career structure for radiopharmaceutical

scientists, and3.facilitate freedom of movement around the conti-

nent.

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Under the auspices of the European School of NuclearMedicine (ESNM), and in collaboration with severalEuropean Universities and Institutes, the Radiophar-macy Committee of the European Association ofNuclear Medicine (EANM) has established a Europeanpost-graduate specialisation certificate in Radiophar-macy. This certificate may be awarded to students,who, in the view of the ESNM Radiopharmacy Board,are suitably qualified, in that they have:a) acquired a university postgraduate diploma or

attended other equivalent courses teaching the theo-retical components of the radiopharmacy syllabus,

b) completed a three-year period of experience duringwhich they have completed the practical compo-nents of the syllabus,

c) completed a nationally acceptable course on radia-tion hygiene.

Status of the Certificate

Award of this certificate means that, in the view of theEANM, the individual has acquired the theoreticalknowledge and practical experience needed for them toassume responsibility for the small-scale productionand quality control of radiopharmaceuticals. At thepresent time, this qualification carries no legal statusbut it is the hope of the Association that it will, intime, be recognised by the European Union and itsmember states as the appropriate qualification for thoseindividuals managing radiopharmacy departments.

Mechanism for award of the Certificate

Students who have completed requirements (a - c)above and who wish to apply for the certificate shouldwrite to the Chairman of the ESNM RadiopharmacyBoard enclosing the following documentary evidenceof their studies and practical experience:• certificates of attendance at the relevant courses• a check list indicating when and where they have

gained practical experience• signed letters from the heads of departments in

which they have gained this experience confirmingthis to be the case.

The Board will review the documents and, if they arefound to be acceptable, then the Board will recommendthe award of the certificate to the Dean of the Euro-pean School of Nuclear Medicine. If necessary,arrangements will be made for the student to sit a

Board examination paper at a mutually convenienttime and place.

Radiopharmacy Courses

In order to simplify the organisation of courses thatteach the syllabus for this qualification, it has beendivided into three modules or Blocks:Block 1: Pharmacy;

Block 2: Radiopharmaceutical chemistry;

Block 3: Associated subjects.

At the present time the following courses have beenpresented or are planned:

• INSTN, Paris, (Block 2): November 2000• ETH Zürich (Block 2): 19th Feb. - 2nd March 2001• INSTN, Paris, (Block 3): spring 2001• University of Frankfurt (Block 1): autumn 2001• University of Leipzig (Block 3): spring 2002

3.2 Purdue University Nuclear Pharmacy Training Programs

Kara Duncan, Purdue University, West Lafayette, Indiana, USA

The Purdue University Nuclear Pharmacy CertificateProgram (NPCP) was developed as a tool for trainingpharmacists for the practice of Nuclear Pharmacy. Theprogram is a two-part training tool consisting of a vid-eotape based distance-learning module as well as anintensive two-week on-campus session. The certificateprogram is designed to provide the fundamental back-ground concepts essential to nuclear pharmacy prac-tice. The NPCP, along with the undergraduate trainingprogram, the graduate research program and anadvanced clinical clerkship for Pharm.D. students areintegrated to meet the core nuclear education goalsestablished by our department.

As part of the current revision process, the originalprogram is being modified to better reflect present daypractice and enhance the clinical skills necessary fordaily practice in a nuclear pharmacy. The videotapeportion of the program is being converted to a digitalformat to allow for current use as high quality video-

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tape or for future modification to computer based orinternet based delivery as technologic advances permit.The videotape material itself is being enhanced usingdigital editing techniques, digital graphics and practicalreal world examples. Clinical cases are used to supple-ment the learning process, as are practical lab scenarios.

With this revision, the Nuclear Pharmacy CertificateProgram is moving toward the use of more technologi-cally advanced teaching methods. In addition to theupdate of the videotaped material, the inclusion ofinternet based teaching resources like WebCT™ allowthe students to more easily participate in the distancelearning program. Internet testing with instant feed-back has been established, as well as on-line chat roomsand discussion forums, all of which are designed toallow our trainees to interact easily with the faculty atPurdue, as well as with other trainees in the program.The site can also be used as a reference source and as aforum for future learning opportunities after the train-ees have completed the program.

As a result of our current revision plans, the develop-ment of an internet-based database will lend itself wellto incorporation in our program. The material devel-oped will supplement our training process in an easilyaccessible manner. Together, the two formats can beused to greatly enhance the training of nuclear pharma-cists.

3.3 Radiopharmaceutical Compounding and Dispensing in Australia

Peter Eu, Peter MacCallum Cancer Institute, Melbourne, Australia

The radiopharmaceutical regulatory affairs of Australiaare governed by the Therapeutic Administration Act(TGA), which allows some professionals to compoundand dispense radiopharmaceuticals under certain condi-tions. These professionals must have appropriatelicenses to handle radioactive materials.

Nuclear Medicine Physicians are allowed to compoundand dispense radiopharmaceuticals in their practice.For accreditation as a Nuclear Medicine Physician, thephysician has to complete basic courses in the nuclearmedicine sciences, including radiopharmacy. Thisradiopharmacy course is provided by the Australian

Nuclear Science and Technology Organization(ANSTO). It has a modular format that is taught onsite, but course notes are provided before attendance atthe course. Each module has prescribed learning out-comes, and the trainee is assessed by tests that includewritten short answer questions and multiple-choicequestions. The Nuclear Medicine Physician traineemust receive practical training in an accredited Depart-ment and this training must involve the trainee in rou-tine radiopharmacy procedures including qualityassurance. The training Department is also required tohave access to a radiopharmacist or radiochemist to dis-cuss radiopharmaceutical sciences.

Nuclear Medicine Technologists are allowed to com-pound and dispense radiopharmaceuticals under thedirect supervision of a Nuclear Medicine Physician.These technologists are usually taught Radiopharmacypractices for one and a half years in their senior years ata technical school. They then have to take a one-yearinternship post graduation in which radiopharmacypractice is part of the program.

Pharmacists are allowed to compound and dispenseradiopharmaceuticals throughout Australia, depend-ing on the conditions under which they practice. Thereis a very limited introduction to radiopharmacy in theundergraduate programs of pharmacy degree programs.Training to be a radiopharmacist can be obtained eitheron the job, or through a postgraduate certificate inradiopharmacy that is jointly offered by the VictorianCollege of Pharmacy, Monash University and the Soci-ety of Hospital Pharmacists of Australia. This certifi-cate course is conducted via distance learning withtutorials and a minimum of two weeks full time resi-dential practice at an approved radiopharmacy site.

Radiochemists are also allowed to compound and dis-pense radiopharmaceuticals in public hospitals withintheir State or Territory of practice. Their education inradiopharmacy can be obtained on the job or throughthe ANSTO course.

Other professions such as biomedical engineers andhealth physicists may be allowed to compound and dis-pense radiopharmaceuticals, depending on the circum-stances of the facility in which they are employed.Their education and training are usually obtained on

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the job and through courses offered by institutionssuch as ANSTO.

Several Universities in Australia are developing post-graduate courses leading to certificates, diplomas, andMaster of Applied Science degrees, all with specializionin Medical Radiation Science and with Radiopharmacyas a major subject. These courses may not necessarilybe involved with any pharmacy school at present. Asthe sciences component in radiopharmacy practicedoes not change anywhere in the world, a commonbackground teaching course in radiopharmacy such asthe one proposed in this workshop would be of valueto the radiopharmacy practitioners including physi-cians, pharmacists, and nuclear medicine technologistsin Australia. This will not only allow the principles ofradiopharmaceutical sciences to the uniformly taughtto the intending practitioners, but also serve as a refer-ence resource to the current practitioners and inter-ested professionals.

3.4 Radiopharmacy Training at the University of Alberta

John Mercer, Steve McQuarrie and Len Wiebe, Faculty ofPharmacy and Pharmaceutical Sciences, University ofAlberta, Edmonton, Alberta, Canada

A high percentage of the senior practicing radiophar-macists in Canada were trained at the University ofAlberta. The historical basis for this fact rests on morethan three decades of radiopharmaceutical research inthe Faculty of Pharmacy and Pharmaceutical Sciencesat the University of Alberta. This provided an infra-structure and a highly trained and experienced facultyfor student instruction. The faculty has had isotopeproduction facilities, first through the installation of aCockroft-Walton Accelerator and later with the com-missioning of a research reactor. This capability will beenhanced within the next year with the opening of acyclotron/PET center at the University.

The core of radiopharmacist training is provided by aseries of undergraduate and graduate courses offered inthe Faculty of Pharmacy and Pharmaceutical Sciences.These include introductory and advanced radiophar-maceutical sciences, radiation biology, radiopharma-ceutical chemistry and specialized courses in neutronactivation as well as individualized research projects.

Internship training in Edmonton has been provided inconjunction with the Edmonton RadiopharmaceuticalCenter which is a centralized production facility pro-viding products to local hospitals. The radiopharma-cists graduate at the Masters of Science (M.Sc.) levelwith mentoring by established researchers and involve-ment with peer reviewed research projects. Many haveachieved Ph.D. degrees with additional course andresearch work.

We have tested the concept of distance learning in agraduate course on radiotracer methodology in 1999,where a section of lectures on the physics of radioactivedecay were provided over the Internet. A detaileddescription of this pilot project is discussed in Section 5.

4 TARGET GROUPS FOR COMPUTER/INTERNET-BASED, RADIOPHARMACY-ORIENTED COURSE MATERIALS (THE UNITED STATES PERSPECTIVE)

David L. Laven, University of Kansas, Kansas City,Kansas, USA

When considering radiopharmacy-oriented educationalcontent for identified “target groups” (pharmacists,radiochemists, supportive personnel in clinical andresearch settings, etc.), we can prepare a basic coregroup outline of topic areas. Additionally, we can alsodevelop the content of these topic areas with sufficientdepth so as to meet the needs of more than one profes-sional discipline. In terms of providing a “basic” knowl-edge base with global rather than limited applicabilitywe must;• provide information in such a way that individuals

select those items they deem applicable to theirrespective professional areas of interest, or developtopic areas with varying degrees of depth so that aprofessional with extended content requirementswill have all the information laid out before them.

• be aware of the “regulatory” attitudes that exists invarious regions of the world.

• take into consideration any unique expectations interms of education and training that must be satis-fied.

The present faculty of the International Radiopharma-ceutical Education Consortium (IREC) has the exper-tise to create a programme of instruction that will meetthe varying needs of professionals regardless of wherethey reside and practice.

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We will have the distinct opportunity to provide a har-monized approach to nuclear pharmacy education andtraining to various groups and organizations, academicand regulatory in nature. There are regions of theworld where established expectations and requirementsfor nuclear pharmacy education and training alreadyexist, and there will be others that are in more forma-tive stage of development.

Nuclear Pharmacists and their Training

In the United States many pharmacy students partici-pate in a 6-year program that culminates in receiving aDoctor of Pharmacy degree (Pharm.D.) Formerly, apharmacy student would participate in a 5-year pro-gram and earn a Bachelor of Science (B.S.) degree. Themajor difference between the Pharm.D. program andthe conventional 5 year Bachelor of Science (B.Sc.)degree is an additional year of rotational “clerkship”learning experiences (non-paid, applied clinical) wherepharmacy students spend one-month intervals in clini-cal areas such as internal medicine, pediatrics, geriat-rics, oncology, drug information, and sometimesnuclear pharmacy. Internships, on the other hand, areoften on-site training experiences (paid positions) thatoccur in one professional setting over longer periods oftime (i.e. months) during a summer recess in-betweenacademic years, or as an evening position during theschool year. Typically, in 6-years of “traditional” didac-tic education in a pharmacy school, a student wouldencounter only 4 to 6 contact hours in nuclear phar-macy. During the upwards of 2000 contact hours ofpractical professional experience the trainee mayreceive only a one-month (approximately 160 hours)experience in a nuclear pharmacy setting. This ishardly a sufficient platform upon which to expect anypharmacy student to demonstrate a suitable apprecia-tion for or interest in nuclear pharmacy.

In the United States there are a few pharmacy schoolsthat offer expanded didactic and experiential opportu-nities in nuclear pharmacy. This is in part to satisfy theU.S. Nuclear Regulatory Commission (or individualstate offices of radiation control) which requires anyindividual who handles and uses by-product (radioac-tive) materials to have completed 200-contact hours ofdidactic training and 500 hours of experiential trainingin nuclear pharmacy. Some of these extended programsexist at schools associated with the Universities of

Arkansas, Butler, Duquesne, Massachusetts, New Mex-ico, Ohio State, Purdue, and Temple. The number ofstudents that matriculate from these programs maytotal no more than 50 to 60 individuals per year. Thereare at present only two post-graduate programs (theMedical University of South Carolina, and the U.S.Army) that offer a one-year residency or fellowship innuclear pharmacy and they provide an additional 3 to 5trained individuals per year. Few of the individuals par-ticipating in these nuclear pharmacy programs con-tinue their studies to receive a Masters of Science(M.Sc.) or doctorate (Ph.D.) degree. Consequently, asacademicians that are more senior approach retire-ment, the question of where to find qualified educatorsto replace them looms ever greater.

A booklet that contains a compilation of documentsand articles pertinent to nuclear pharmacy educationand training from various regions of the world hasbeen circulated at this Workshop. These items canserve as a guide in our ensuing discussions and projectdevelopment efforts for considering what already exists(or is being discussed – “draft form”) in terms ofnuclear pharmacy education and training, from an aca-demic, professional (practice guidelines), and regula-tory perspective. Many of these documents highlightissues that will be important to the planned effort.(Editor’s note: these documents can be obtained bywriting to Dr. Laven). One of these documents, enti-tled Nuclear Pharmacy Practice Guidelines, serves asthe basis for the development of testing for Board-certi-fication (and then re-certification 7 years later) inNuclear Pharmacy by the Specialty Council onNuclear Pharmacy of the Board of Pharmaceutical Sci-ences (BPS). In 1978, Nuclear Pharmacy was the firstarea recognized as a “specialty” in pharmacy by theBoard of Pharmaceutical Specialties.

Another document, entitled Syllabus on Nuclear Phar-macy Training5, serves as a blueprint for developingthe didactic and experiential content. Other docu-ments, including the (proposed) Nuclear PharmacyCompounding Guidelines5, serve as guidelines foraddressing more specific topic areas in nuclear phar-macy.

5 Contact David Laven for source documents.

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In the United States before a pharmacy student can sitfor the National Pharmacy Licensing Examination(NAPLEX), they must document having participatedin 2000 hours of experiential training in recognizedareas of pharmacy practice. Many state boards of phar-macy do not recognize undergraduate experiences innuclear pharmacy as constituting acceptable pre-profes-sional experience. Therefore they do not counttowards the contact hours needed to sit for theNAPLEX. Out of the several hundred questions con-tained on the NAPLEX, there may be only 1 or 2 thataddress any issue relative to nuclear pharmacy practiceand therefore most pharmacy schools and state boardsof pharmacy view nuclear pharmacy as an area that isreserved for postgraduate learning situations.

Although several pharmacy schools continue to offerundergraduate programs for their students in nuclearpharmacy it has become fashionable and necessary tomake available short-course, certificate-training pro-grams in nuclear pharmacy. These programs rangefrom 6-weeks to a few months and can be completedvia on-site or through correspondence, home-study, ora combination of the two approaches. These programsare available to pharmacy students who attend schoolswhere opportunity in nuclear pharmacy educationdoesn’t exist, and help to re-train existing practicingpharmacists who desire a career change and enternuclear pharmacy. Presently, Duquesne, Ohio State,and Purdue pharmacy schools offer a certificate-train-ing program. Syncor International operates its owncorporate short-course program which is accredited vialiaison with Butler University.

Training Nuclear Pharmacy Technicians

At present, basic training programs for pharmacy tech-nicians are available through local (2-year) communityor junior colleges or business-vocational schools, butnone have any direct ties to existing pharmacy schoolprograms. Additionally, there is no pharmacy techni-cian training program today in the United States thatcan prepare an individual for a career in nuclear phar-macy. On-the-job training has been common in manypharmacy settings over the years, but this approach isfalling from favor in order to stress more formal, struc-tured educational approaches. There is obviously anopportunity for a well-prepared, broad ranging andstructured education program to fill this void in

nuclear pharmacy technician training. For this reason,the project that we are undertaking, to develop a vir-tual, internet education program and text in nuclearpharmacy, becomes all that much more important. Infact, when one considers both the short- and long-termgoals, this is an undertaking that will surely achievecritical acclaim.

Training Academic and Research Specialists

The academic and research specialists who currentlydeal with the field of “nuclear pharmacy” or “radiop-harmacy” are in general recruits from allied disciplines.They will have received a combination of formal andinformal training and self-education in radiopharma-ceutical sciences in order to reach their specialist status.These individuals have a wide diversity of backgroundsincluding pharmacy, chemistry, physics, medicine andbiological sciences. Although a few universities mayhave the ability to provide this specialist training inradiopharmacy it is in general acquired in a less formalmanner. This situation presents both an opportunityand a challenge since it should be possible to generate adatabase with sufficient content to meet the educa-tional needs of technical personnel and also pharma-cists, radiochemists, and perhaps even physicians whodesire to specialize in the radiological sciences. In theend, the scope of this project could be broad enough tomeet the needs of many different professional “targetgroups” the world over.

5 DEVELOPMENT OF A COURSE MATERIALS DATABASE TO SUPPORT RADIOPHARMACEUTICAL SCIENCE TRAINING

Steve McQuarrie, John Mercer and Len Wiebe, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada

The information and demonstration module presentedat the Tübingen-Bühl Workshop on Teaching Radiop-harmacy was taken from the didactic radiopharmacytraining program at the University of Alberta. Onegoal of this module was to provide a distance-basedlearning component to both undergraduate and gradu-ate level course offerings. By providing some of the lec-tures in this manner, class time was made available forother uses such as a problem-based learning segment inwhich the students would tackle real-world problemsusing information received from our Internet material.This approach was tested in a graduate course on

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radiotracer methodology in 1999, where a section oflectures on the physics of radioactive decay were pro-vided over the Internet.

Following consultations with the computer sciencegroup the University of Alberta, the software package,WebCT™, was selected as the host program to containand manage our material. In addition to providing amechanism to deliver text-based information,WebCT™ facilitates:• inclusion in the text of figures, hot-links to inter-

nal/external web sites, animation and video,• chat rooms for student-student and student-instruc-

tor discussions,• assignment and automatic marking of problem sets

and exams,• maintenance of student records, and• the capacity to perform virtual lab experiments.

A PowerPoint presentation may be viwed as a demonstration of the operationof our distance-learning approach.www.ualberta.ca/~csps/JPPS4(2)/S.McQuarrie/RadiopharmacyOnTheWeb.htm

Figure 1: Graphical interface for the virtual GM lab.

As part of this program, a virtual laboratory exercisewas designed using Authorware™ (Macromedia). Thislab involved the half-life determination of severalunknown radionuclides, using a GM counter. All com-ponents were designed by a graphic artist under ourdirection to provide a life-like experience, including a“lab cleanup”. Help files were included to direct thestudent in the operation of the virtual detector, andoutlined a set of experiments to be performed. A com-pressed time system was used to speed up data acquisi-

tion, and student-selectable time points were used tocollect activity data far into the future to determinehalf-lives of long-lived radionuclides, such as C-14. Thegraphic interface for this virtual lab is depicted in Fig-ure 1. Readers interested in this program are referred toSteve McQuarrie. [email protected]

6 COPYRIGHT ISSUES IN DEVELOPING PUBLICLY-ACCESSIBLE COURSE MATERIALS

Clyde Cole, Amersham, USA

The International Radiopharmaceutical EducationConsortium (IREC) proposed to develop educationalprograms that would provide consistency within thearea of radiopharmaceutical education and training forinterested individuals. IREC agreed on the program inprinciple. Questions then arose about protecting theintellectual property of the worldwide experts thatcomposed IREC and the programs that were beingdeveloped. Investigation of the subject provided almostas many questions at it did answers. Discussionexplored the aspect of protection of created programsand property with the idea in mind that the materialwould be available on the worldwide web.

Copyright

Copyright protection generally means that certain usesof the work are lawful only if they are done with theauthorization of the owner of the copyright. Includedin the protection is the right to copy or otherwisereproduce any kind of work. “In the United StatesConstitution, copyright was intended as an incentivefor scientific, artistic or other creative achievement. Itallows the author of a work to retain the sole rights tocopy or distribute that work for a certain period oftime”6. The intent of the Copyright was not to restrictaccess to these works. The idea behind copyright wasto allow authors retention of the rights to their work;hopefully stimulating them to create more worksthereby increasing their creative effort.

“Existing copyright law recognizes the tensionbetween the needs of society and the rights of creatorsby permitting a defense against charges of infringementfor certain uses of copyrighted works as specified insections 107-110 of the U.S. Copyright act of 1976.Among these uses are: the fair use of copyrighted

6 Pfaff-Harris, K, Copyright issues on the Web (I-TESL-J)

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http://www.ualberta.ca/~csps/JPPS4(2)/S.McQuarrie/RadiopharmacyOnTheWeb.pdf

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works for teaching, scholarship or research, amongother activities; the reproduction of copyrighted worksby libraries and archives under certain conditions forspecific purposes; and the performance or display of awork by instructors or pupils in the course of face-to-face instruction”.7

It is generally accepted that for whatever purpose youare using the “copyrighted” information, you shouldget permission from the author if for no other reasonthan professional courtesy. Permission is consideredessential.

Laws from “state to state”, meaning political entities,very significantly. In an effort to bring some consis-tency to the process and hopefully develop and main-tain the protection of rights of authors, the WorldInternational Property Organization, WIPO, hasamassed significant information pertaining to the sub-ject of copyrighting. They have available on their web-site, the entire text of the “WIPO Copyright Treatyand the agreed statements of the Diplomatic Confer-ence that adopted the Treaty and the provisions of theBern Convention (1971) referred to in the Treaty(WIPO Copyright Treaty) (1996))”.

Copyright Registration

The US Copyright Act protects the material created assoon as it is reduced to a tangible form. It is unneces-sary to register. What registration does, however, isallow the creator the chance to 1) sue for damages; and2) recover statutory damages. Even the fact that yourwork is protected upon fixation, you cannot sue some-one until the work is registered with the Copyrightoffice. Additionally if registration is done within 3months of the first date of publication, or prior to thedate of infringement, statutory damages can be col-lected. Should there be no registration only actualdamages can be collected. Statutory damages can beawarded up to $100,000 plus attorney fees and courtcosts.

Copyrighting essentially provides proprietary protec-tion. Within that framework are several parametersincluding, but not limited to; cost to users, utilizationrights and ownership. One of the problems with elec-

tronic availability is the ease with which an individualcan plagiarize the original work.

Pfaff-Harris also points out “Many web browsers auto-matically copy every page to a cache on the user's harddrive, thus technically violating copyright. (The UShas tentatively decided that this in not a violation ofcopyright, but that printing or 'WebWhacking' a sitemay be.) In general, viewing a website or printing apage from the site is acceptable, as long as the author iscredited with the work”.8

Plagiarism, the taking of someone's work and submit-ting as your own, is an easy project for the less thanambitious student and many times difficult to detect.Frequently the intent is to borrow a phrase or two or aparagraph or two and meld them into the treatise.What in fact happens is that more than the one or twoparagraphs or statements are plagiarized and, in somecases whole pages and even documents, are incorpo-rated without reference or permission.

Julie J.C.H Ryan, in her article “Student Plagiarism inan Online World”9 addresses the fact that “Before theworld was linked by the Internet, hard-to-detect plagia-rism required ingenuity and skill. But today, with theclick of a mouse, even technologically inept studentshave access to vast information resources in cyberspacewithout having to leave the comfort of their dormrooms”. She also notes “A few words typed into a Websearch engine can lead a student to hundreds, some-times even thousands, of relevant documents, makingit easy to 'cut and paste' a few paragraphs from hereand a few more from there until the student has anentire paper-length collection. Or a student can find aresearch paper published in one of the hundreds ofnew journals that have gone online over the past fewyears, copy the entire text, turn it into a new docu-ment, and then offer it up as an original work withouthaving to type anything but a cover page. Even recy-cling efforts and ghost writers have gone global, withWeb sites offering professionally or student-writtenpapers for sale, some even with a money back guaran-tee against detection”.

7 National Humanities Alliance, Basic Principles for Managing IntellectualProperty in the Digital Environment, Mar 1997, www-ninch.cni.org

8 Paff-Harris, K, Copyright issues on the Web (I-TESL-J)9 Ryan, Julie, J.C.H, Student Plagiarism in and Online World, www.asee.org/prism/december

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There are obviously many questions that arise whenconsidering ownership of intellectual property in gen-eral. Those questions are even more complex when theworldwide web is the medium for the dissemination ofthat property. Among the questions are: Who owns it?How are the owners protected? Who gets the money?Administration and control of the material is essentialif the authors are to be compensated for their efforts.Does this require an international license of some sort?Is there even such a license available? Do you need indi-vidual country licenses, or possibly a “national collabo-rative license? How will licensing fees be handled?With whom or where should the copyright be regis-tered?

Utilization rights become an issue when there is agroup of international experts responsible for creationof various parts of the program. When that occurs,how are utilization rights determined? How do the col-laborators work together without competing whenthey are agents of separate organizations that naturallycompete?

The area of fees raised even more questions. Will therebe University fees that would be due to the Universi-ties that many of the IREC participants were associatedwith? Would “private” user fees be possible to organiza-tions such as independent training schools?

Commercial fees are another consideration as is howmuch “good will” availability will there be, if any? Fur-ther decisions concerning fees are related to how theywill be levied. Per unit basis, per hour of use basis, perCE basis, per topic basis? And finally who gets whatportion of the fee, or should there be a standardizedremuneration?

Many of these questions can only be answered by theorganizers, and while the issue of protection seems tobe addressed by international organizations (likeWIPO), there is still uncertainty in the globalization ofthat protection.

7 COMMITTEES TO BE ESTABLISHED

• Steering (Management) Committee• Content group• Technology group• Finance committee (to be appointed when appropriate)

The Working-group should function as an interna-tional consortium (IREC). Matters to be discussed andapproved relate to:

Licensing considerations

• Fee is for access, payable annually• License the using organization for the year• Technology group to address access restriction

aspects

Consortium composition

• IREC membership would initially consist of thosewho were present at the Bühl 2000 Workshop.

• New contributors may be invited to participate.• Maintain the status quo of the committee for a year

and reevaluate at next year's Bühl meeting.• Fair remuneration for contributors is to be decided

by committee.

Action

• Each workgroup is to produce a report or theiractivities before they leave Bühl. This should be pre-sented as a one-page recapitulation of the commit-tee's progress.

• All presenters were requested to turn in a text basedabstract version of presentations and provide thepresentation electronically to the recording secre-tary if possible.

• Participants were requested to provide any com-ments in electronic form.

8 STEERING (MANAGEMENT) COMMITTEE REPORT

Members:Clyde Cole – Recording SecretaryPeter CoxPeter EuHans-Jürgen MachullaGerrit WesteraLeonard Wiebe

The committee identified issues important to theadvancement of the project. • Publication of the Workshop proceedings.• The Management Group nominated Peter Cox to

explore the possibilities for funding. The letter ofsolicitation would reflect sources of funding and

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identify those contributed financial, technical andintellectual resources.

• The Technology Group will research and recom-mend the medium platform to be used for the edu-cational programs. This group will also identifypersonnel resources to complete the initial phase ofdevelopment.

• Funding allocation decisions will be made based onthe financial resources acquired to fund the commit-tee’s short and long-term objectives.

• A number of management issues were identified,including formal recognition of editors and creatorsof units, the establishment of user-fees and budgetplanning.

9 REPORT OF TECHNOLOGY/MEDIA SUB-COMMITTEE

Members:Georg BeckerKara DuncanSteve Mather – Recording SecretarySteve McQuarrieHans Jörg Rahm

Distribution

Universally compatible format will be developed toprovide easy adaptation to the needs of individualcourse organisers and end-users.

Learning material will be distributed via a centralserver mirrored to (4-5) sites throughout the world butcontrolled through the central server. The need wasidentified to keep these mirror sites virus free. Likely /possible server sites could be in:

• Canada: Edmonton• USA: Purdue• Europe 1: Tübingen• Europe 2: London • Pacific: AustraliaIndividual chapters/sections should also be made avail-able on CD-ROM. A companion workbook could beproduced either internally by the group or by an exter-nal publisher. Local organisers could produce (elec-tronic) logbooks.

Format

This should be made compatible with current browserssuch as Netscape and Internet Explorer. Microsoft“FrontPage” will be the recommended software pack-age. A template will be developed containing:

• Title, subtitle, fonts, background (plain), format forgraphs, images, equations and chemical structures,recommended plug-ins

Instruction to authors

Detailed instructions will be developed to reduce theneed for editorial input. Material must be supplied in aform compatible with the template. The authors willbe encourages to do as much as possible in terms ofweb page design. They should also identify topics thatrequire professional graphic design/animation andinclude further supplementary material, exam ques-tions/problems with answers, and reference/readingmaterial. There will be a suggested limit of two screenlengths to limit the need for scrolling. Authors willhave editorial access to final version before release.

Features of the material

Several “core features” were identified to facilitate userinteraction with the knowledge database. External datalinks will be limited to those with non-critical contentand guaranteed continued access. Otherwise internallinks will be preferred and other web publishers will beapproached for permission to download their material.Different coloured text will be used for external andinternal links. Printing capability could use PDF for-mat or possibly text (rtf) format and will be includedwhere appropriate. Material will contain a ‘Water-mark’ or other copyright notice. Each topic should alsoinclude an email link to authors of that material.

Access

Security: Users need to register (non optional) beforeaccess will be granted to the databases. Suggested userprofiles would include name, password, position, insti-tution (address and phone number) and/or emailaddress.

Registration: Benefits will include notification ofupdates and formal recognition and certification fol-lowing course completion.

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Access Fees: Access may be sponsored by a local aca-demic institution or may be purchased on-line. If accessfees are a requirement, then a mechanism for chargingmust be developed.

Resource EstimatesSome central resources have been identified and thecommittee recommends that these be located at theUniversity of Alberta (Canada). Required personnelinclude one person with computer/secretarial skills fulltime (US $20K) and 1-2 graphic artists/animators (US$35K each) at an estimated total cost of US $100,000/yr.

10 COURSE CONTENT SUBCOMMITTEE - INTERIM REPORT

21/JULY/00

Committee Members:Daniela GündischAkli HammadiBernd JohannsenDavid LavenJohn Mercer (Recording Secretary)Gerald ReischlFrank RöschStan Shaw (Chair)Wolfgang Wiegrebe

A number of general principals were adopted by thecommittee to provide a working base for discussion:

• Course material will be suitable for a wide ratherthan a narrow audience. This would include individ-uals who would work in a controlled and supervisedenvironment (technicians) and others who wouldwork with a high level of independence (develop-mental radiochemists and radiopharmacists).

• The content would be focused at an intermediatelevel of detail and difficulty.

• Additional content would be added to or linked tothe intermediate level program to satisfy the needsof more advanced students.

• The requirements of the European and NorthAmerican users are recognized to be different butoverlapping. The European program would be mostneeded to educate students at a graduate level whohad no background in pharmacy but would have astrong science education (chemistry). The North

American program would have the primary focus ofeducating pharmacists to become radiopharmacists(nuclear pharmacists).

• The majority of didactic material is immediatelyavailable from members of the workshop group.This material is in a variety of formats and on avariety of media (WEB based, electronic text, video-tape, graphics etc.). The content subcommittee willbe guided by the technical subcommittee in thepreparation of these materials in a suitable style andformat.

• The content subcommittee will rely on all membersof the workshop group and not just members of thesubcommittee in the preparation and organizationof materials.

• Contacts and resources outside of the control of theworkshop members will not generally be used inthe preparation of course materials unless a clearneed is identified.

• The content will include both practical informationand theoretical background. This is regarded asimportant since the intent is to educate scientists aswell as technicians.

• Some theoretical aspects of the course will be pre-sented at an elementary level with links or refer-ences to more advanced and rigorous information.This allows a varied audience to be accommodated.

• Some topics will be presented in more than onelocation within the overall course material. This isrequired if the material is to maintain a modularcharacter. For example a description of the ionizingability of radiation would occur in a discussion ofinteraction of radiation with matter and again whenthe topic of radiation effects on biological systemswas considered. In some instances this materialcould be linked while in others it might have to beorganized or presented in a different manner.

The committee agreed to consider the document“Nuclear Pharmacy / Radiopharmacy Training Guide-lines” as a starting point for discussion of content. Thisdocument outlines suggested content for a course inNuclear Pharmacy. The material has been examinedpreviously by the International Harmonization inNuclear Pharmacy Committee on Education. Duringthe subcommittee deliberations of this document anumber of changes were suggested and implemented.The document which appears in Section 12 incorpo-

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rates these changes and is recommended as the workingdocument to guide the workshop members in the selec-tion and organization of course materials. Severalmajor alterations were incorporated into these guide-lines based on the subcommittee discussions:

• An introduction section was added.• Additional weight was suggested for the radiochem-

istry section to make it more appropriate for theEuropean requirements.

• A section that deals with legal aspects and guidelinesand adherence to regional Pharmacopeia would beadded as a final section. This material would neces-sarily be generic but could be linked to specificnational or regional information.

• A section was added which considered in vitro andin vivo analysis of new radiopharmaceuticals andthe legislative aspects of bringing a new agent intoclinical practice. Again this material would begeneric with links to regional specific data.

Further discussion centered on the requirement foradditional educational materials for students withoutformal education in pharmaceutical science. ProfessorWiegrebe of Universität Regensburg presented thecommittee with a document entitled “SupplementaryEducation of Radiochemists in Pharmacy”. This mate-rial was accepted as a model for the preparation of asupplementary package of educational material thatcould be developed to complete a program that wouldbe more comprehensive in the European setting. Thismaterial would not be part of the initial developmentof course content but could be considered once othercontent has been completed.

Subcommittee goals:

Short term: 3 months.• Circulation of the detailed table of contents to

workshop participants for final evaluation. Thetable of contents has been modified to conformwith the wishes of the subcommittee as identifiedduring the workshop and will be revised if addi-tional issues are identified in the review process.

• Identification of existing resources and assignmentof committee and other workshop members to areasof interest or expertise.

• Identification of sections of course material thatwould be applicable for three levels of users; (techni-

cian, intermediate and scientist).One-year goal.• Detailed preparation of one or more major sections

of the required materials based on the format anddesign provided by the technical subcommittee. Theaim will be to produce a module that is completeand adheres to all requirements identified by thetechnical committee.

• Assignment of responsibilities for further coursematerial development.

• Presentation of a timeline for completion of thepreparation of all remaining course materials.

11 EUROPEAN RADIOPHARMACY SYLLABUS (THEORY COMPONENTS)

Block 1:Pharmacy • Pharmaceutical Technology• Implications of Good Manufacturing Practice• Sterile Manufacture• Pharmaceutical microbiology• Parenteral Products• Formulation and Packaging

Pharmaceutical Analysis• Pharmacopeial monographs• Quality Assurance and Product Performance • Quality Control Procedures• Stability and Shelf Life• Regulations and Legal Aspects• Marketing Authorisations• Responsibilities of Personnel

Block 2:Radiopharmaceutical chemistry • History of radiopharmaceutical chemistry• Physics of radioactivity• Properties of carrier-free substances, separation

techniques• Production of radionuclides in nuclear reactor and

cyclotron• Targetry, nuclear chemistry, generators• Synthesis of labelled compounds

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• Purity and stability of labelled compounds, radio-nuclidic and radiochemical purity

• Radionuclides in analytics, autoradiography• The radiotracer principle• Criteria for radiopharmaceuticals• Production of radiopharmaceutically relevant radio-

nuclides

• 99mTc-generator

• 99mTc-radiopharmaceuticals I, basics

• 99mTc-radiopharmaceuticals I, kit preparation• Other radiometals• Radioiodination• Cell labelling

• PET-radiopharmaceuticals (18F, 11C, 13N, 15O)• Animal models, animal protection regulations • Radiotracer transport, pharmacokinetics, modeling

Practical Components of the Radiopharmacy SyllabusDuring a three-year period of work in a radiopharmacydepartment the student should gain a sufficient practi-cal experience in the following areas as to be able toperform these duties independently and to be able toassume responsibility for supervising others undertak-ing these tasks in the future. If the students own placeof work is not able to provide the full-range of facilitiesnecessary to gain this experience then either they ortheir supervisor should make arrangements to work fora period of time in another department of Radiophar-macy, Pharmacy or Nuclear Medicine where the neces-sary resources are available. Students should feel free tocontact a member of the Radiopharmacy Board foradvice if needed.

a) Operation of a GMP facility that provides fullcontrol of the environment, materials, procedures,equipment, and personnel involved in the prepara-tion of radiopharmaceuticals.

b) Working in a sterile environment:• aseptic-technique, • monitoring personal technique,• monitoring the environmentc) Design and application of a quality assurance

programme.

d) Use of safe radiation practices,• procedures for personal dose limitation and moni-

toring • contamination monitoring• accidents involving radioactivity• local and national regulations and procedures• radioactive waste disposale) Documentation of radiopharmaceutical

procedures: • Information should be provided on standard operat-

ing procedures, product and equipment specifica-tions, records of radiopharmaceutical preparation,analysis and other processes.

f) Use, maintenance and calibration of equipment used:

• radioisotope calibrator (ionisation chamber): accu-racy, constancy, linearity and geometry effects.

• contamination monitors: efficiency, minimumdetectable activity

• (gamma) scintillation counters: efficiency, resolu-tion, minimum detectable activity, counting statis-tics

• liquid scintillation counter: efficiency and countingstatistics

• laminar flow hoods/radioisotope work-stations• centrifuges, autoclaves, balancesg) Procurement of radiopharmaceuticals• Types and limits of radionuclide material that can

be ordered • Ordering radiopharmaceuticals: consideration of

purchase orders, suppliers, ordering schedules andtimes, precalibration times and record keeping,including familiarity with computer procedures.

• Receipt of radiopharmaceuticals: delivery proce-dures, trace of delayed shipments, surveys, wipetests, radioassay, packaging, disposal, storagerequirements, and record keeping logs.

h) Radiopharmaceutical preparation:

• Elution of a 99Mo-99mTc generator; quality control of eluates.

• Preparation of 99mTc radiopharmaceuticals using ‘kits’.

• Preparation of ‘in-house’ radiopharmaceuticals (non-kit).

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• Labelling of red and white blood cells.• Protein radio-iodination.• Preparation of PET radiopharmaceuticals.i) Quality control of radiopharmaceuticals• Radionuclidic purity using gamma-ray spectros-

copy.• Radiochemical purity using absorption methods,

thin-layer chromatography, solid-phase extractionand HPLC methods

• Chemical purity: pH• Particle size of particulate radiopharmaceuticals: fil-

tration, light microscopy• Pharmaceutical acceptability: visual inspection, ste-

rility, freedom from endotoxin (Limulus test)j) Supply of radiopharmaceuticals: Dispensing, labelling, allocation of control numbersand expiry dates, packaging, transport.k) Participation in research and development

projectsl) Presentation of work at an open scientific meet-

ingm)The student should also gain the following gen-

eral experience:• two weeks in a centre preparing PET radiopharma-

ceuticals or single-photon radiopharmaceuticals ifthis is not included in their three year experience

• two weeks in a clinical department of Nuclear Med-icine including direct handling of patients, opera-tion of imaging equipment, interpretation of imagesand quantitative data

• one week in a department performing radioimmu-noassay

12 IREC PROPOSED CURRICULUM

The purpose of these guidelines is to describe basic fun-damentals and concepts important to the assurance ofquality radiopharmaceutical products and services topatients. The guidelines are relevant to radiochemists aswell as nuclear pharmacists engaged in small-scale prep-aration and quality assurance of radiopharmaceuticals.They are not directed toward a person engaged inresearch and development of radiopharmaceuticals norto an individual specializing in services in P.E.T. Theknowledge and basic concepts listed may be obtainedby formal lecture-laboratory exercises, directed self-

paced study or combinations of these approaches toeducation.

INTRODUCTION

I. History of Radiopharmaceuticals

II. Radiotracer Principals

III. Criteria for Selection of Tracers

RADIATION PHYSICS AND INSTRUMENTATION

I. Structure and Properties of Atoms

A. Atomic Models, NomenclatureB. Nuclides and Radionuclides

1. isotope, isobars, isotones, isomers2. chart of the nuclides

C. Orbital Energy Levels1. energy units: eV, keV, MeV2. electron shell binding energy, excitation

and de-excitation3. characteristic X-rays, Auger electrons

D. Mass and Energy IntraconversionE. Other Nuclear Considerations

II. Radiation and Radioactive Decay

A. Radiation1. defined2. principal forms

B. Nuclear Stability and Radioactive DecayC. Radioactive Decay Law and EquationsD. Units of RadioactivityE. Half-life and Decay ConstantF. Types of Decay

1. alpha2. negatron (beta minus)3. positron (beta plus)4. electron capture5. isomeric transition6. spontaneous fission

G. Consideration of Radioactive Decay Processes1. disposition of decay energy2. beta energy spectrum3. neutrinos4. beta only vs. beta-gamma emission5. annihilation reaction

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6. characteristic X-rays7. Auger electrons8. isomeric transition9. metastable states10. internal conversion

III. Decay Schemes of Radionuclides used in Nuclear Medicine

A. Chart of the NuclidesB. Sequential DecayC. Growth of Radioactive DaughtersD. Transient EquilibriumE. Secular Equilibrium

IV. Interactions of Radiation with Matter

A. Excitation and IonizationB. Positive Particle Interactions

1. mechanism of excitation and ionization2. alpha particle, positron and heavy ion

interactions3. specific ionization4. annihilation radiation

C. Electron Interactions1. excitation and ionization2. Bremsstrahlung

D. Neutron InteractionsE. Photon Interactions

1. photoelectric effect2. Compton scatter3. pair production

V. Instruments for Radiation Detection and Measurement

A. Ion Collection Methods (Cutie Pie, Pocket Dosimeters, Proportional Counters, Dose Calibrators, and G-M detectors)1. ionization chambers2. current-voltage relationships

a. simple ionizationb. primary and secondary ionizationc. proportional regiond. Geiger regione. pulse vs. currentf. calibration

B. Scintillation Detectors1. principles of operation

2. calibration3. use4. quality control5. external solid crystals6. internal liquid scintillation7. pulse height analyzers

a. single channelb. multichannelc. gamma cameras, PET cameras

C. Gamma Cameras, PET CamerasD. Film Emulsions

1. film badges2. X-ray, radiological films3. autoradiography

E. Thermoluminescent DetectorsF. Solid State Detectors

VI. Nuclear Reactions

A. Accelerator/Cyclotron Production of Radionuclides

B. Reactor Production of Radionuclides

MATHEMATICS OF RADIOACTIVITY USE AND MEASUREMENT

I. Radioactivity

A. Radioactive Decay Law and EquationsB. Units of Radioactivity

1. traditional2. SI

C. Half-life and Decay ConstantD. Decay Tables (construction and use)E. Nuclear Counting Statistics and Measurement

II. H��

A. Inverse Square LawB. Half Value LayerC. Linear Attenuation CoefficientD. Mass Attenuation Coefficient

III. Radiopharmaceutical Preparation and Dispensing Calculations

A. ActivityB. ConcentrationC. VolumeD. Pre- and Post-calibration Decay Tables

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E. Particle NumberF. Expiration TimeG. Specific Activity

IV. Generator Operation and Use

A. Calculations to Determine Parent Activity over Time

B. Calculations Using Transient and Secular Equilibrium Equations to Determine:1. daughter activity-time profiles following

elution2. theoretical yields3. elution efficiency4. parent-daughter-granddaughter nuclide

cascade

V. Calculations Involved with Radioactivity Measurement and Counting Statistics

A. Accuracy, Precision and Percentage Error of Radiopharmaceutical Dosage

B. Mean, Standard Deviation, Probable ErrorC. Background CorrectionD. Geometry Correction

VI. Quality Assurance Calculations

A. Radionuclidic, Radiochemical and Chemical Purity of Radiopharmaceuticals

B. Dose Calibrator Accuracy, Constancy, Linearity and Geometry

C. Scintillation Counter1. efficiency2. dead time3. resolving time4. precision5. minimum and maximum detectable

activity

VIII.Calculations Associated with the Quantitative Assessment of Radiopharmaceutical Absorption, Distribution, Metabolism and Excretion

A. In vivo Function StudiesB. In vitro StudiesC. Kinetic Studies

IX. Calculations Involved with Medical Decisions

A. SensitivityB. Specificity

C. AccuracyD. Predictive Diagnostic Value

X. Radiation Dosimetry Calculations

A. MIRD EquationB. Internal Dose EquivalentsC. External DoseD. Bioassay

RADIATION PROTECTION AND REGULATIONS

I. Interactions of Radiation with Matter

A. Excitation, Ionization, Energy DepositionB. Specific Ionization; Linear Energy Transfer

(LET)1. comparison of gamma radiation and

particulate radiation2. range in matter3. relative hazard as external and internal

sources

II. Units of Radiation Measurement

A. Roentgen (R)B. Radiation Absorbed Dose (RAD)C. Gray (Gy)D. Radiation Biological Equivalents (RBE)E. Radiation Equivalent Man (REM)F. Quality Factors (QF) or Radiation Weighting

FactorG. Sievert (Sv)H. External and Internal Dose Limits

III. Occupational and Non-Occupational Exposure Radiation Protection Guides

A. National Council on Radiation Protection and Measurements (NCRP)

B. International Commission on Radiological Protection (ICRP)

C. As Low as Reasonably Achievable (ALARA) Program

IV. Principles of Radiation Protection

A. Time of ExposureB. Distance from Source (Inverse Square Law)

1. specific gamma ray dose constant2. exposure dose calculations

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C. Shielding1. half-value layer and attenuation

coefficients2. determination of shielding requirements

a. type of materialb. thickness needed

D. Automation/Remote ControlE. Quantity/Amount of Radiation (Radiation

Accidents)

V. Personnel Monitoring and Precautions

A. ALARA1. concept, scope, and implementation2. exposure of the embryo/fetus3. exposure of the public4. occupational exposure limits

B. Restricted, Controlled and Unrestricted AreasC. Effective Dose EquivalentsD. Monitoring Devices

1. film badges2. ring badges3. thermoluminescent dosimeters (TLD's)4. pocket dosimeters5. other types of dosimeters

E. BioassaysF. Precautionary Warning (Caution) SignsG. Reports and Notices

VI. Area Monitoring (Personnel and Work Environment)

A. Surveys, Wipe Tests and Monitoring Intervals Required in Work Areas Where:1. radioactive material is stored or2. compounded, dispensed or administered3. unrestricted areas

B. Limits of Radiation Contamination and Exposure1. in work areas (restricted)2. unrestricted areas

C. Air Monitoring1. airflow velocity measurements - hood and

room2. restricted and unrestricted areas

VII. Radioactive Packages and Sources

A. Procedures for Opening Radioactive Packages

B. Requirements for Shipment of Radioactive Material (General Considerations)1. packaging2. labeling3. transport index4. shipping papers5. placarding of vehicles6. removable contamination survey

C. Monitoring Sealed Sources (Leak Tests)

VIII. Radioactive and Biohazardous Waste Disposal Methods (General Considerations)

A. Decay in StorageB. Separation by Half-LifeC. IncinerationD. Sewer or Atmosphere

IX. Radiation Safety

A. Laboratory Techniques for Handling Radioactive Material Safely

B. Laboratory Design1. minimizes potential for radioactive

contamination and radiation exposure2. proper placement of hoods and sinks3. location of storage, compounding,

dispensing, quality control, and waste areasC. Regulatory AgenciesD. Quality Management PlanE. Radiation Safety CommitteeF. Radiation Safety Officer

X. Radiation Accidents

A. Emergency ProceduresB. Major and Minor SpillsC. Industrial Accidents/Environmental IssuesD. Decontamination Procedures

1. facility2. personnel

E. Incident Reporting

RADIATION BIOLOGY

I. Interactions of Radiation with Emphasis on Biological Systems

A. General ConceptsB. Aqueous Systems

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C. Factors Affecting Reactions1. oxygen2. concentration3. LET

D. Application to Basic Compounds and Macromolecules1. types of molecules; enzymes, DNA, RNA2. structural changes3. influence of dose, dose rate, LET, and

oxygen

II. Cellular Response

A. Effects on CellsB. Sensitive OrganellesC. Concept of RadiosensitivityD. Response to Increasing Radiation DoseE. Factors Influencing Response

1. dose rate and dose fractionation2. LET3. oxygen4. cell type and cell cycle

III. Effects on Nucleic Acids

A. Structural ChangesB. Synthesis and ReplicationC. Mechanism(s) of RepairD. Influence on Cell Cycle

IV. Radiation Genetics (Hereditary Effects)

A. Gene EffectsB. Chromosomal EffectsC. Assessment of Risk

V. Effects of Ionizing Radiation on the Embryo and Fetus

A. Mechanism and ConsequencesB. Assessment of Risk (Teratogenic and Delayed

Effects)

VI. Whole-Body Effects of Ionizing Radiation

A. Overview of Radiation Exposure of Tissues and Organs

B. Hematopoietic TissueC. Gastrointestinal TractD. SkinE. Reproductive Organ

F. Nervous SystemG. Respiratory SystemH. Circulatory SystemI. Urinary SystemJ. Musculoskeletal SystemK. Endocrine OrgansL. Sensory Organs

VII. Acute Effects of Ionizing Radiation

A. Bone Marrow SyndromeB. Gastrointestinal SyndromeC. Cerebrovascular SyndromeD. Influencing Factors

1. type of radiation and area of exposure2. dose, dose rate, and dose fractionation

VIII. Delayed Effects of Ionizing Radiation

A. Occurrence, Risks and Types of ExposureB. Hereditary Effects (see also Radiation

Genetics)C. Somatic Effects

1. cancer induction2. life span shortening?3. organ fibrosis and degeneration

IX. Low Level (Low Dose) Exposure to Ionizing Radiation

A. Sources1. medical2. natural background3. radon

B. SignificanceC. Radiation Hormesis

RADIOPHARMACEUTICAL CHEMISTRY

I. Introduction

A. Distinction between Radionuclides, Radiochemicals and Radiopharmaceuticals

B. Criteria for Radiopharmaceuticals1. suitable radionuclides for diagnosis and

therapy (nuclear physical properties, biological and effective half-life, metabolism, availability)

2. design of radiopharmaceuticalsC. History of Radiopharmacy

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D. Legislation1. principles and guidelines of good

manufacturing practice for radiopharmaceuticals (encl. nuclear pharmacy practice guidelines)

2. monographs for radiopharmaceuticals

II. Production of Radiopharmaceutically Relevant Radionuclides

A. Accelerator/Cyclotron Produced Radionuclides1. nuclear reactions, activation equation2. targetry3. separation and purification

B. Reactor Produced Radionuclides1. nuclear reactions, activation equation2. targeting3. separation

C. Radionuclide Generators1. mathematical principles2. use and advantages3. applications4. quality assurance

III. General Physicochemical Properties of Radioactive Compounds

A. Physical Properties1. decay mode2. photon energy3. particulate energy and range4. half-life5. chemistry6. in vitro stability

B. Activity-Mass RelationshipC. Tracer Concentration Expressions

1. specific activity2. concentration

D. Carrier Concept/Designations (Carrier-Free, Carrier Added, No Carrier Added)

E. Solution Chemistry of Tracer Radionuclide Metals1. hydrolysis2. reduction-oxidation3. complexations reactions4. radiolytic decomposition

IV. Types of Radiopharmaceuticals According to Their Mode of Distribution and Localization

A. Introduction into Radiopharmacology1. distribution2. metabolism3. excretion4. pharmacokinetics

B. Cells, Particles and Colloids1. capillary trapping2. phagocytosis and pinocytosis3. distribution volume, increased capillary

permeabilityC. Radioimmunodiagnostic and

Radioimmunotherapeutic Agents: LabeledAntibodies and Fragments, Peptides

D. Biochemical Substrates and Ligands1. enzyme substrates and inhibitors;

metabolic trapping2. receptor-binding agents

E. Small Nonspecific Molecules1. distribution and diffusion2. compartmental space3. chemisorption

V. Labeling

A. Types of Labeling: Isotopic vs. Non-isotopic Labeling

B. Labeling with Radiometals1. small metal complexes2. kinetic and thermodynamic aspects of

radiometal complex chemistry3. bifunctional chelators

C. Radiohalogenation1. strategies of fluorine-18 labeling2. methods of radioiodination3. radiobromine and Astatine-211 labeling

D. Carbon-11 Chemistry1. Preparation of precursors,2. C-11 -methylations and other methods

E. Cell Labeling I1. Direct labeling,2. Indirect labeling

VI. Quality Control of Radiopharmaceuticals

A. Radionuclidic Purity1. gamma scintillation spectrometry

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2. differential attenuationB. Radiochemical Purity (i.e. Chromatographic

and Other Separation Methods)C. Chemical Purity (i.e. Chromatographic

Methods)D. Visual Inspection (i.e. Color, Clarity, Particle

Size and Number of Particles)E. pH MeasurementF. Sterility TestingG. Endotoxin TestingH. Cell ViabilityI. Antigen-excess

VII. Technetium-99m Radiopharmaceuticals

A. Molybdenum Mo-99/Technetium Tc-99m Generator1. production schemes2. operation3. wet vs. dry column4. quality control5. generator physics6. specific activity

B. Technetium Chemistry1. oxidation states and coordination modes2. reduction methods3. technetium tin-ligand reactions in aqueous

solutiona. hydrolysisb. reoxidationc. complexationd. carrier effectse. radiolytic decomposition

C. Technetium Kits (i.e. Preparation and Composition)

D. Specific Kits (i.e. Methods for Radiolabeling with Tc-99m)1. human serum albumin2. macroaggregates and microspheres3. phosphonates4. glucoheptonate5. HMPAO and ECD6. isonitriles, tetrofosmin7. MAG3 and EC8. DMSA9. antibodies

E. Other Tc-99m Radiopharmaceuticals

VIII. Rhenium-186 and Rhenium-188 Radiopharmaceuticals

A. Tungsten-188/Rhenium-188 Generator1. operation2. quality control

B. Specific Rhenium Radiopharmaceuticals1. Re(V)DMSA2. Re HEDP3. Re labeled antibodies and peptides4. Re loaded stents

IX. Iodine Radiopharmaceuticals

A. Radioiodine Isotopes for Radiopharmaceuticals: I-123, I-124, I-125, and I-131

B. Chemistry of RadioiodideC. Specific Radioiodinated Radiopharmaceuticals

1. sodium iodide1. radioiodinated albumin2. ortho-iodohippurate3. meta-iodobezylguanidine (MIBG)4. iodocholesterol5. amphetamines6. proteins7. monoclonal antibodies8. peptides9. molecular recognition units (MRU's)10. neuro-transmitter ligands

D. Dosage Forms AvailableE. Safety Techniques for Handling Radioiodine

X. Fluorine-18 Radiopharmaceuticals

A. Radionuclide ProductionB. Remotely Controlled and Automated

RadiosynthesesC. Specific Fluorine-18 Radiopharmaceuticals

1. fluoride2. fluorodeoxyglucose (FDG)3. L-6-fluoro-DOPA4. receptor ligands

XI. Radiolabeled Blood Cells

A. Methods for Blood Cell Separation Prior to Labeling

B. Tc-99m Red Blood Cells (i.e. in vitro, in vivo and Modified in vivo Methods of Labeling for

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Blood Pool Studies and Detection of Gastrointestinal Bleeding)

C. Tc-99m Red Blood Cells (Heat Damaged) for Spleen Specific Imaging

D. In-111 White Blood cells (i.e. Methods of Radiolabeling for Abscess Localization)

E. Cr-51 Red Blood Cells (i.e. Methods of Radiolabeling for Blood Volume Measurement)

F. In-111 Platelets (i.e. Methods for Radiolabeling)

G. Tc-99m White Blood cells (i.e. Methods for Radiolabeling for Abscess or Inflammation Detection)

H. Interaction with Drugs on Cell Labeling Procedures

XII. Prepared Radiopharmaceuticals

A. Thallium-201 ChlorideB. Indium-111 DTPA, Labeled Peptides and

ProteinsC. Phosphorous-32 Sodium PhosphateD. Cobalt-57/58 Cyanocobalamin (Schilling test)E. Radioactive Gases (i.e. Xenon Xe-133, Xe-127,

Krypton Kr-81m)F. Gallium-67 CitrateG. Strontium-89 ChlorideH. Yttrium-90 Citrate, Labeled Antibodies and

Peptides, MicrospheresI. Stannous-117m DTPAJ. Samarium-153 EDTMPK. Copper-64 and Copper 67 Labeled

BiomoleculesL. Miscellaneous

XIII. Radiopharmaceutical Development

A. Approaches and Trends1. empirical approaches to design2. rational approaches to design structure/

distribution relationshipB. Animal Models

THE CLINICAL USE OF RADIOPHARMACEUTICALS

I. Criteria for the Selection of the Appropriate Radiopharmaceutical

II. In Vivo Kinetics of Radiopharmaceuticals

A. Absorption, Distribution, Metabolism, Elimination

B. Normal vs. Abnormal KineticsC. Factors that Affect/Alter the Kinetics of

Radiopharmaceuticals

III. Specific Procedures Which Employ Radiopharmaceuticals

A. IndicationsB. Optimal Diagnostic or Therapeutic ProtocolsC. Interventional Techniques Which Enhance the

ProcedureD. Interpretation of the Procedure Outcome, Its

Effect on Patient Management, and Its Economic Implications

E. Sensitivity, Specificity, and Predictive Value of Diagnostic Procedures

F. Expected Benefits of Therapeutic Procedures

IV. Preparation and Monitoring of Patients Who Receive Radiopharmaceuticals

A. Patient Education and Preparation/Family Counciling

B. Precautions and Considerations for Special Patient Populations1. pediatric patients2. pregnancy testing3. breast feeding4. others

C. Dosage Adjustment Based on Age, Weight, Body Surface Area, Organ Function, Instrument Sensitivity, etc.

D. Clinical Problems Associated with the Use of Radiopharmaceuticals1. adverse reactions/untoward effects2. misadministration/reportable events3. unusual or unanticipated images or

therapeutic outcomesa. artifactsb. altered radiopharmaceutical

biodistribution due to interference from drug therapy or surgical intervention; radiopharmaceutical formulation problems; improper administration techniques, etc.

c. variations in human anatomy

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E. Correlation Between the Results of Product Quality Control Testing and Clinical Outcome of the Procedure

F. Use of Radiopharmaceuticals to Monitor the Safety and/or Efficacy of Specific Drug Therapy Regimens

G. Drug Information Resources for Nuclear Medicine and Nuclear Pharmacy

H. The Role of the Nuclear Pharmacist as Consultant and Provider of Patient Specific Information

IV. Introduction to Design of a Nuclear Pharmacy

A. FacilitiesB. OrganizationC. Equipment

LEGAL ASPECTS AND NATIONAL AND INTERNATIONAL GUIDELINES

I. Guidelines from United States Pharmacopeia and European Pharmacopeia

II. In Vitro and in vivo Evaluation of New Radiopharmaceuticals

A. Biological Testing and Other Types of Evaluation

B. Legislative Aspects

Research and development applications

I. Radiopharmacology (animal models, in vitro assays, tissue culture)

A. Introduction to the use of radiopharmaceuticals in research

B. The use of radiopharmaceuticals in researchC. Radioreceptor assays: Principle, Technology

and ConceptsD. Tissue culture modelsE. Animal models, animal protection

Regulations

II. Biopharmacy of radiopharmaceuticals

A. Formulation: Galenics of radiopharmaceuticalsB. Vectorisation of radiopharmaceuticals

III. Toxicology

A. Methods of toxicity assessment of the preparation of radiopharmaceuticals

B. Meeting regulatory requirements

IV. New trends in radiopharmaceuticals

A. ImmunotherapyB. Aspects of biochemistry and molecular

biology: Antisense technologies in diagnosisC. Developments on gene therapyD. Radiopharmaceuticals based on bioactive

peptides (Detection of tumours, infection/ inflammation and thrombus)

E. New trends on targeted radiotherapyF. Therapy control using PET and nuclide pairs

(I-124 PET, I-131 Therapy, 86Y PET, 90Y Therapy)

V. Clinical trials of radiopharmaceuticals

13 CONCLUSION

The second IREC workshop will be held in Rotten-berg, Germany in June 2001 to finalize the plans forimplementing a distance-based learning program inradiopharmaceutical sciences. An international appeal,to potential sponsors, is being launched to generatefunding to finance specific projects within the pro-gramme.

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