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Jean-Pierre CABOCEL
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AGENDA I. Who is AIPESII. Evolution of Healthcare
III. Nuclear MedicineIV. Supply of raw materialV. Next steps
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ASSOCIATION OF IMAGING PRODUCERS &EQUIPMENTS SUPPLIERS
AVENUE LOUISE 65 B1050 BRUXELLESwww.aipes-eeig.org
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CYCLOPHARMALABORATOIRES
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Executive CommitteeMarc Gheeraert, President & Secretary GeneralVittorio Puppo, Vice PresidentGuy Turquet de Beauregard, Vice President
Director GeneralJean Pierre Cabocel
Working Groups
Regulatory Affairs
Gerhard Vollberg
Covidien
New Technologies
Thomas Beyer
Reactor & Isotopes
Bernard David
IRE
Transport
Charlie Carrington
GE Healthcare
Admini st rat ionJocelyne Baldasso
Law FirmJean Luc Laffineur
Team RA Team New Tech Team R&I Team TR
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MISSION
Imaging & Therapy with Molecular and Radioactive Tracers
Promote Nuclear Medicine & Molecular HealthcareLobby for Appropriate Regulations & Funding Push for Cost Effectiveness and InnovationacceptanceSupport & Facilitate Logistics and Operations
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Patients safetyFull compliance: adoption of all relevant requirements, both onradioactivity and pharmaceuticalsCompliance covers the entire process: from R&D, to manufacturing, todistribution, to any after sale events
InnovationTradition of innovation and commitment to novel, future tracersDevelopment of new drugs will require a more tailored regulatoryapproach
Healthcare for everyoneEnsuring products and technology availability for all requiredprocedures all over Europe
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Diseaseprogression
Geneticpredis-position
First cellmutations
asympto-maticdisease
Diseased cells releasebiological markers
First symptoms/manifestation
diseaseproliferation
Environmental trigger
Current approach
Symptoms
Imaging
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Mortality &treatment costs
Diseaseprogression
Geneticpredis-position
First cellmutations
asympto-maticdisease
Diseased cells releasebiological markers
First symptoms/manifestation
diseaseproliferation
Environmental trigger
Current approach
Symptoms
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Mortality &treatment costs
Diseaseprogression
Geneticpredis-position
First cellmutations
asympto-maticdisease
Diseased cells releasebiological markers
First symptoms/manifestation
diseaseproliferation
Environmental trigger
Molecular Medicine approach
Molecular Diagnostics
Current approach
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Mortality &treatment costs
Diseaseprogression
Geneticpredis-position
First cellmutations
asympto-maticdisease
Diseased cells releasebiological markers
First symptoms/manifestation
diseaseproliferation
Environmental trigger
Molecular Medicine approach
Current approach
Earlierin Care Cycle
Symptoms
Molecular Diagnostics
Source: Philips Medical Systems
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Major Health ConcernsBrain and Degenerative Diseases
OncologyCardiology
Major InvestmentsResearch & Development
Diagnostic Equipment & InfrastructureTherapyHomecare
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THE RIGHT BALANCEINFLUENCED BYIndustry Type
Consumer Ethics
Environment
Breakthrough
Economic Viability Market Volume
Public Opinion
Regulatory&
Compliance
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In Vivo Imaging Modalities for Research & Diagnostic
after: Meikle et al., Phys. Med. Biol. 50 (2005) R45-R61
LimitingResolution
Depth of Penetration
MRS
smart MRI
Bioluminescense
Fluorescense
smart U/S
SPECT
PET
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In Vivo Imaging Modalities for Research & Diagnostic
after: Meikle et al., Phys. Med. Biol. 50 (2005) R45-R61
LimitingResolution
Depth of Penetration
MRS
smart MRI
Bioluminescense
Fluorescense
smart U/S
SPECT
PET
-ATP
-ATP-ATP
PCr
GPC
GPE
PiPC
PE
31 P Liver spectrum
(Courtesy Vanderbilt University, USA)
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The Imaging Application for Metabolism
Small lesion detectionTherapy efficacyNew drug development
Gateway to Molecular Healthcare
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New product introductionLegislation not specific for Radio-pharmaceuticalsGMP
Availability of raw material& Opportunities
Installed base of thousands of cameras Same technology, high resolution and available in hybrid 9-15 year life cycle, lower purchase cost.
Innovation through Molecular Healthcare Imaging
Therapy
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10001FDA
App roved Agen t
DRUG DEVELOPMENT
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35 million procedures (2nd Imaging Technique afterCT, before MR)
20 USA9 Europe3 Japan
3 ROW
28 million of Tc99m
2 million of FDG
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Cardiac Imaging 12 millionProcedures
Tc 99mTl 201
Bone 10Tc 99m
Lung 5Tc 99m
Thyroid 5I 131 / 123Tc 99m
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Imaging:conventional, single
photon emissiontomography SPECT,
SPECT/CT
Imaging: positronemission
tomography(PET, PET/CT,
PET/MRI)
Therapy, pain palliation,radioimmunotherapeutics
67 Ga (a) 18 F(a) 67 Cu (a) 131 I(r)
99m Tc/ 99 Mo(r)(g) 61 Cu(a) 89 Sr(r) 153 Sm(r)
111 In(a) 64 Cu(a) 89 Zr(a) 169 Er(r)
123 I(a) 68 Ga/ 68 Ge(a)(g) 90 Y/90 Sr(r)(g) 177 Lu(r)
131 I(r) 82m Rb/ 82 Sr(a)(g) 90 Y(r) 186 Re(r)
133 Xe(r) 89 Zr(a) 117m Sn(r) 188 Re/ 188 W(r)(g)
201 TI(a) 124 I(a) 123 I(a) Alpha emitters,e.g. 213 Bi/
225 Ac (g) (a)Production route: (r)=reactor, (g)=generator, (a)= accelerator
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SPECT Agent Phase Application99 Tc-metronidazole A RadioRx efficacy99 Tc-Humanaspect A GI cancer 99 Tc-CEAscan A GI/Breast Cancer 99 Tc-NeoTect A Lung cancer 111 In-Prostascint A Prostate cancer 111 In-Zevalin A NHL111 In Octreoscan A Neuro tumors123 I Ioflupane A Parkinson90 Y-Zevalin A NHL90 Y-Octreother A Neuro tumors99 Tc-sestamibi III/A Drug Resistance99 Tc- annexin V II Chemo efficacy99 Tc-deoxyglucose I Tumors188 Re-deoxyglucose I Tumors188 Re-annexin V I Tumors188 Re-metronidazole I Tumors188 Re-sestamibi I Tumors90 Y-Prostascint I Prostate cancer
PET Agent Phase ApplicationFDG A Tumor MetabolismRb A PerfusionF-Dopa III Dopamin-receptor FLT I ProliferationFMISO I Hypoxia
MRI Agent Phase ApplicationGd-DTPA A Perfusion
SPIO A Liver-Tumor MS325-Albumin A Blood-PoolGd-Fibrin I Thrombus
US Agent Phase Application
Microbubble A PerfusionMicrobubble I Breast Tumor
Optical Agent Phase Application ALA-IX A Tumor Metabolism
Molecular Imaging and Therapy Agents
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Industry follows two types of regulations formanufacturing radiopharmaceuticals:
Pharmaceuticals
RadioactiveHigh level of investment
Radiopharmaceuticals are considered aspharmaceutical drugs since 1989
(Directive 89/343/CEE)
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ProductionPharmaceutical LaboratorycGMP(current Good Manufacturing Practice)
Marketing approval
Nuclear Safety & RadioprotectionFacilitiesTransportation
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Objective = to obtain a pure pharmaceutical-graderadionuclide
3 methods :By irradiation of non-radioactive element with protons incyclotrons (cyclotron activation method)
By irradiation of non-radioactive element with neutron inreactor (reactor activation method)
By irradiation of uranium 235 target in reactor to createfission by-products (fission by-product method)
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Cyclotron phase :Proton irradiation in cyclotrons of the target to
generate radioactive isotopesRadiochemical phase in labs :
Transfer of the irradiated target from cyclotron to aradiochemistry laboratoryChemical purification of radioisotope (as Thallium201 or Fluor 18) from the target
Radiopharmaceutical phase in labs :Manufacturing of radiopharmaceutical (e.g.Thallium or FDG vials) in pharmaceutical conditions
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Reactor phase :Neutron irradiation in approved reactor of the stableisotope target to generate radioactive isotopes
Radiochemical phase in labs :Transfer of the irradiated target from reactor to aradiochemistry laboratoryChemical purification of radioisotope (as Samarium 153)from the target
Radiopharmaceutical phase in labs :Manufacturing of radiopharmaceutical in
pharmaceutical conditions
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REACTOR
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Reactor phase :Neutron irradiation in approved reactor of the highlyenriched uranium 235 (HEU) target to generate fissions
Radiochemical phase in specialized producerlabs:
Transfer of the irradiated target from reactor to aradiochemistry laboratoryChemical extraction and purification of fission by-
product (e.g. Molybdenum99
) from the targetRadiopharmaceutical phase in labs:
Manufacturing of radiopharmaceutical (e.g.Technetium generator) in pharmaceutical conditions
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Reactor European Licensed Supplier
NRG Petten (NL) X
CEA Osiris (Fr) X
MOL BR2 (Bel) X
AECL NRU (Can) X
Safari NTP (AFS) X
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Specialized producer European Licensed Supplier Covidien (NL) X
IRE (Bel) X
Nordion (Can) X
NTP (AFS) X
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Specialized producer European Licensed Supplier
Covidien (NL) X
IBA - CisBio (F) X
Nordion (Can) X (not commercialised)
GE (UK) X
MAP (Fin) X
Monrol (Turk) X
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What Happened
In the Summer of 08 ?
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Petten Mol Saclay RSA CanadaPhaseI. Irradiation
Covidien IBA GE MAP Monrol etc MDSPhase III. Generators
Covidien IRE MDSPhaseII. Extraction
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Petten Mol Saclay RSA CanadaPhaseI. Irradiation
Covidien IBA GE MAP Monrol etc MDSPhase III. Generators
Covidien IRE MDSPhaseII. Extraction
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Petten Mol Saclay RSA CanadaPhaseI. Irradiation
Covidien IBA GE MAP Monrol etc MDSPhase III. Generators
Covidien IRE MDSPhaseII. Extraction
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Petten Mol Saclay RSA CanadaPhaseI. Irradiation
Covidien IBA GE MAP Monrol etc MDSPhase III. Generators
Covidien IRE MDSPhaseII. Extraction
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Petten Mol Saclay RSA CanadaPhaseI. Irradiation
Covidien IBA GE MAP Monrol etc MDSPhase III. Generators
Covidien IRE MDSPhaseII. Extraction
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Petten Mol Saclay RSA CanadaPhaseI. Irradiation
Covidien IBA GE MAP Monrol etc MDSPhase III. Generators
Covidien IRE MDSPhaseII. Extraction
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Petten Mol Saclay RSA CanadaPhaseI. Irradiation
Covidien IBA GE MAP Monrol etc MDSPhase III. Generators
Covidien IRE MDSPhaseII. Extraction
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Demand & Supply study
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Major currentradionuclide
production reactors
by country/location
Name
Design
thermal
powerMW
Thermalflux
cm -2s -1
Fuel Criticalitymonth
Status Operating days
per year
(nominal)
Australia, LucasHeights
OPAL 20 1.0X10 14 20%LEU
AUG 06 Oper (age2)
?
Belgium, Mol BR2 100 3.5x10 14 93%HEU
JUN 61 Oper (age47)
120Canada, ChalkRiver
NRU 135 1.5x10 14 20%LEU
Nov 57 Oper (age51)
270France, Saclay OSIRIS 70 1.0x10 14 20%LE
USEP 66 Oper (age
42)180
The Netherlands,Petten
HFR 45 1.5x10 14 20%LEU
NOV 61 Oper (age47)
270
South Africa,Pelindaba
SAFARI-1
20 0.75x10 14
20%LEU
MAR 65 Oper (age43)
310
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Major potentialfuture
radionuclideproduction
reactors
Country/location
Name
Design
thermal
powerMW
Thermal flux
cm -2s -1Fuel Criticalit
y monthStatus
Operating days
peryear
(nominal)France,
CadaracheRJH 100 1.3X10 1
5
20%LEU
_ Underconstruction (operating
2015)
250?
The Netherlands,Petten
PALLAS
45 2.0x10 14 LEU _ Planneddate notdecided
280
South Africa SAFARI-2
? ? LEU _ Planned ?
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Other current
radionuclideproduction
reactors
Country/location
Name
Design
thermal
powerMW
Therma
l flux
cm -2s -1Fuel Criticalit
y monthStatus
Operating
days peryear
(nominal)
Czech Rep., REZ LVR-15 10 1.5X101
4 36%HEU SEP 57 Oper (age51) 200Germany, Munich FRM II 20 8X10 14 93%HEU
MAR 04 Oper (age 4) 250
Korea, Taejon HANARO
30 4,5X10 14
? FEB 95 Oper (age13)
150?
Poland, Otwock-
Swierk
MARIA 30 4,5x10 1
4
36-80%
HEU
DEC 74 Oper (age
34)
280
Argentina, Ezeira RA-3 5-10 1x10 14 20%LEU
AUG 68 Oper (age40)
230
USA, Columbia,
Missouri
MURR 10 6x10 14 ? Oct 66 Oper (age
42) currentlyno 99 Moproduction
280?
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Reactor Schedule 2009
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January 2009Th F Sa Su M Tu W Th F Sa Su M Tu W Th F Sa Su M Tu W Th F Sa Su M Tu W Th F Sa
01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
HFR PettenOSI SaclayBR2 Mol
Safari PelindabaNRU Chalk Riv.
February 2009
Su M Tu W Th F Sa Su M Tu W Th F S a Su M Tu W Th F Sa Su M Tu W Th F Sa01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
HFR PettenOSI SaclayBR2 Mol
Safari PelindabaNRU Chalk Riv.
week 5
week 6 week 7 week 8 week 9
Week 1 week 2 week 3 week 4
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Short TermRefurbish existing dedicated reactorsIncrease medical application in existing dedicatedreactorsUpgrade existing research reactors for medicalapplication.
Long TermUse Horowitz reactor for MolybdenumBuild a dedicated medical reactor with backupNew technology
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