finnish boron neutron therapy (bnct) program år on · bnct utilizes the neutron capture reaction:...

BNCT utilizes the neutron capture reaction: r0B

captures thermal neutrons emitting c-particles andrecoils 7li *itn high linear energy transfers. Crucialin BNCT is selective uptake of boron by the tumor.The dosimetric problems consist of boronconcentration measurements in tissues, energyspectrum of neutron beam, and neutron fluencedistribution in tissues. Characterization of thetreatment beam is the basis of the dosimetry in BNCTand it provides an experimental verification of thecomputer models of the beam. Dosimetry is

complicated by the admixture of thermal, epithermal,and fast neutrons, and 1 rays. The treatments areplanned to be started with boronophenylalanine(BPA) which has been used in clinical trials.

INTRODUCTION

BNCT is one of the most complex cancer therapeuticmodalities, and its ultimate success is dependent on howadequate concentrations of boron and neutrons can be

delivered to the tumor [1].In Finland a research group to carry out clinical

application of BNCT for malignant brain tumors was

established in the early 1990's. The planning formodifying the thermal column of the VTT researchreactor for neutron source was started at the same time as

the clinical research for boron carriers in HUCH [2].From the beginning of this year the research has been

extended to all fields of BNCT. The overview focuses on

the present scientific projects on BNCT in Finland.

NEUTRON SOURCE

The Finnish research reactor (FiR 1) operated by theTechnical Research Cenfre of Finland is a 250 kWTRIGA II pool reactor with the inherently safe specialTRIGA uranium-zirconium hydride fuel. Based onnumerical modeling, a new optimal neutron moderatormaterial composition was developed for epithermalgeneration [31. The patented material is a composition ofAlF3 (69m-Vo), aluminum (30m-Vo) and LiF. Themanufacturing process based on the hot isostatic pressing

Gm) technique has been developed for the materialpressing solid blrcks with ln% density. The

1 .5.1.02

manufacturing of the needed moderator material will be

completed in February 1996.

DOSIMETRY AND DOSE CONTROL PLANS

Characterization of the treatment beam is the basis ofthe dosimetry in BNCT providing an experimentalverification of the computer models of the beam. Thethermal and part of the epithermal and fast neuftonspecfra can be measured with foil activation analyses.The fast neutron components of the beam have to beverified before clinical trials.

The BF3 chamber can be used to estimate the actualdose distribution in BNCT. The computer simulateddoses due to the neutron and T components have to be

measured in the circumstances identical to the clinicalsituations. Utilizating a combination of tissue-equivalent(TE) and graphite chambers filled with TE and CO2 gas,

respectively, gives the neutrorVgamma dose relation indesired geometry [4].

Standard ro*m (60co and 137cs) of the SecondaryStandard I-aboratory of Finnish Centre for Radiation andNuclear Safety (STUK), Radia-tion Mefiology Laboratoryare used for calibration and testing of the ionizationchambers used for BNCT. The air kerma rates of thestandard sources are traceable to the InternationalStandard at BIPM (Bureau International des Poids etMesures) in France and NPL (National PhysicalLaboratory) in UK. At present forn new ffis ofionization chambers for BNCT dosimetry are available.

The Ge detectors are used to measure the capture 1of10g in the phantom or patient. On-line monitoring of thetreatment field is performed using fission and ionizationchambers. The post treatment dose contol in patientsmay be improved by using conventional TlD-dosimetersparallel to other techniques.

TREATMENT PLANNING

Calculations of the distribution of the absorbed dosefor BNCT are more complex than for photon andelectron therapy. Idaho National Engineering I-aboratory

flNEL) with university collaborators has developed thefirst functioning treatment planning program for BNCT[51. The software was installed fa the use of Finnish

The Finnish boron neutron capture therapy (BNCT) program- år overview on scientific projects

Sauli Savolainenl, Me4a Kallio2, Iiro Auterinen3, Tiina SeppiilälJyrki Viihätalo4 and Martti Kulvik2,

lDepartqent of Physics, University of Helsinki (P.O.Box 9, FIN-00014 Helsinki University).zClinical Research Institute, Helsinki University Central Hospital (HUCH)

3che*ical Technology, Technical Research Centre of Finland ryTf)4laboratory of Radiochemisfiy, University of Helsinki

Medical & Biological Engineering & Computing Vol. 34, Supplement 1, Part 1, 1996The 1Oth Nordic-Baltic Conference on Biomedical Engineering, June 9-13, 1996, Tampere, Finland 301

BNCT research group in December 1994. The efforts ofthe Finnish BNCT researchers are directed to local beam(FiR 1) characterization for the software module.

The treatment planning program for BNCT takes asinput imaging data of anatomical regions of the patient.A software was developed for doing segmentation of themedical image, contour ffacing of segmented image, andB-spline fitting in collaboration with Helsinki Universityof Technology (HLfD, I-aboratory for BiomedicalEngineering .

PHANTOM DESIGNS

The dimensions of the phantom should simulate theanatomy and the materials of the phantom should betissue-equivalent (TE). The compartments for a BNCTheadlike phantom are elliptical covering layers of skin,skull and brains [6]. For a TE-liquid in a BNCT headlikephantom, the simplest choice is water and the mostprecise choice is a brain-equivalent (BE)-liquid. Our BE-liquid is a mixture of water, alcohol, urea and inorganicsalts. A magnesium ionization chamber flushed withargon, or a carbon graphite chamber flushed with carbondioxide, will be used to determine the gamma ray doseand a TE ionization chamber flushed with TE-gas todetermine the neutron dose in phantom.

ANALYSIS OF BORON AND BPA

The Finnish BNCT research gr^oup has been studyingboronated LDL as a potential IUB carrier [7]. protoninduced gamma emission analysis (PIGE), secondary ionmass specfiometry (SIMS), inductively coupled plasmamass spectrometry (ICP-MS), and inductively coupledatomic emission specfrometry (ICP-AES) were tested tomeasure boron in LDL matrix. It was concluded thatPIGE can be an appropriate reference method forchemical boron analysis [8].

The planned treatment approach will be based on theuse of BPA as the boron carrier. The current efforts onboron bulk-analysis with PIGE and ICP-AES are focusedon BPA-matrix. In order to analyze boron distribution atcellular level SIMS and Nuclear Reaction Analysis(NRA) will be used combined with sample preparationmethods (freeze-drying and cryosectioning), whichpreserve the original trace element distribution. Toachieve reliable quantification, a set of l0B-e*ichedstandard slices will be prepared using an isotopeseparator.

A potential labeled marker for probing theeffectiveness of the current boron carrier isradiofluorinated derivate of BPA, i.e. 4-borono-2-JlSflfluorophenylalanine (FBPA). BPA can beradiofluoronated directly by carrier added electrophilicmethods. However, the scientific radiochemical goal ofthe Finnish BNCT program is to label BPA with anucleophilic regioselective no carrier addd (NCA)method.

RADIOBIOLOGY

The normal tissue tolerance studies required for thebiological effects and radiation safety assessments beforeproceeding to treatments with patients. For the studiesadult dogs will be given BPA and different radiationdoses. A one-year follow-up of the dogs will be carriedout. Both clinical and radiological evaluations (MRIscans) of the dogs will be obtained. The study will bedone in collaboration with the Faculty of VeterinaryMedicine at the University of Helsinki.

The Finnish BNCT project is a multidisciplinaryresearch project involving scientists from differentdepaftments of Helsinki University, HUCH, yTT,HUT, and STUK. The aim of this project is to startBNC-treatment in Finland with malignant braintumors by the end of the century.

REFERENCES

tll R.F. Barth, A. H. Soloway, R. G. Fairchild and R. M.Brugger, "Borcn neutron capture therapy for cancer,realities and prospects," Cancer vol20, pp. 2995-3007,1992.

12) P. Hiismiiki, I. Auterinen and M. Ftukkilä, "TheFinnish BNCT program, an overview," in proceedings

of the CUNCT BNCT Worluhop. Helsinki: HelsinkiUniversify of Technology series TKK-F-A718, 1994, pp.2-4.

t3] I. Auterinen and P. Hiismiiki, "Design of anepithermal neutron beam for the TRIGA reactor inOtaniemi," in Proceedings of the CUNCT BNCTWorkslnp. Helsinki: University of Technology seriesTKK-F-A7 18, 1994 , pp. 14-24 .

t4l S. Savolainen, H. Jiirvinen, A. Kosunen, K. Anttila, I.Auterinen and M. Forss, "Dosimehy and dose controlplans for BNCT at Fir-l TRIGA II reactor in Otaniemi."in Proceedings of the CUNCT BNCT Workshop.Helsinki: Helsinki University of Technology series TKK-F-4718, 1994,pp. 46-48.

t5l D.W. Nigg, "Methods for radiation dose distributionanalysis and tratment planning in boron neuhon capturetherapy," Int J Radiation Oncol Biol Phys. vol 28, pp.tI2t-1t32, tgg4.t6l O. K. Harling, K. A. Roberts, D. J. Moulin and R. D.Rougs, "Head phantoms for neutron capture therapy,"Med Phrys, vol22, pp. 579-583, 1995.

l7l J. I-eppälä, M. Kallio, T. Nikula, P. Nikkinen, K.Liewendahl, J. Jiiäskeldinen, S. Savoläinen, H. Gylling,J. Hiltunen, J. Callaway, S. Kahl, and M. Färkkilä,"Accumulation of 99m-Tc-LDL in human malignantglioma," Br J Cancer vol7l, pp. 383-387, 1995.

t8l S. Savolainen, J. Räisåinen, V. Eteliiniemi, U. AboRamadan and M. Kallio, "Analysis of 10-B by pIGE withfrctor analytical tray peak identification," Appl Rd/sol vol 46,W.855-958, 1995.

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