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Targeted Therapies and Clinical Translational Research: Optimization of Clinically Effective Dose and Schedule

>¹⁸F-labeled BPA positron emmision tomography (PET) based Boron Neutron Capture Therapy on malignant glioma patients in Japan

Osaka Medical College, OSAKA, Japan, Kyoto Prefectural University of Medicine, KYOTO, Japan, Kyoto University Reserch Reactor Institute, OSAKA, Japan

Abstract

B79

Boron neutron capture therapy (BNCT) is based upon the nuclear reaction that occur when non-radioactive boron-10 (¹⁰B) is irradiated with low energy neutrons to produce high energy a particles (¹⁰B[n,alpha] ⁷Li). In order for BNCT to be successful, a sufficient amount of ¹⁰B and neutrons must be delivered to the tumor.We have treated a group of 40 patients with high grade gliomas using a combination of surgery followed by BNCT. This was carried out at the Kyoto University Research Reactor Institute (KURRI) using an epithermal neutron beam for enhanced tissue penetration together with use of two different boron drugs, sodium borocaptate (BSH) and boronophenylalanine (BPA), both of which have been used clinically. Forty patients were treated between 2002 and 2006 at Osaka Medical College.¹⁸F-labeled BPA positron emmision tomography (BPA-PET) has been applied for the estimation of the boron compound accumulation prior to BNCT [Imahori Y, Clin Cancer Res,1998]. We use the dose-planning work station SERA to calculate irradiation dose for tumor from BPA-PET data and patients blood sampling data from every 2 hours after BSH administration. Using BPA-PET, the residual tumor:normal brain (T/N) ratio varied from 2.1 to 7.1 (mean 4.0). Tumor boron concentrations of BSH and BPA varied from 17 to 32 µg/g, and from 34 to 98 µg/g, respectively. As a result of these estimation, we decide the neutron irradiation time and the total radiation dose delivered to normal brain was less than 13 Gy-Eq, and the estimated maximum dose delivered to residual tumor was from 44.6 to 64.8 Gy-Eq.Clinical response was assessed by MRI imaging, and this initially revealed a 17 to 71% (mean 51.5%) reduction in the residual tumor enhancing volume and this subsequently increased to 30 to 88 % (mean 61.7%). Reduction in tumor volume and a decrease in edema in brain around the tumor were recognized in many cases.Main causes of die were CSF dissemination and local tumor recurrence from the lesion with low T/N ratio. This could be attributed to an insufficient ¹⁰B(n,alpha) ⁷Li capture reaction in more deep seated regions of the tumor. Nevertheless, there was clear evidence of a favorable response, as evidenced radiographically, and further modifications will be made in the treatment protocol to further improve the clinical results.Analyze the drug accumulation prior to individual treatment was useful for think about therapy effect and for reduce side effect. BPA is accumulated depends on the tumor metabolism of amino acids and it is variable in each cases. So, BPA-PET was very useful for our modified BNCT and this should become important concept for any kinds of cancer targeting therapy in near future.