L-p-Boronophenylalanine (BPA) has been applied as a potential boron carrier for the treatment of malignant glioma in clinical boron neutron capture therapy (BNCT) since 1994. To provide the pharmacokinetics of BPA for clinical use of BNCT in Taiwan, 4-borono-2-18F-fluoro-L-phenylalanine-fructose ( 18F-FBPA-Fr) was synthesized and the biologic characteristics of this radiotracer in glioma-bearing rats were investigated. Methods: Radiolabeled 18F-F2 was produced via the 20Ne(d,α) 18F reaction, and 18F-acetyl hypofluorite ( 18F-AcOF) was generated by passing 18F-F2 through a column filled with tightly packed KOAc/HOAc powder. The effluent containing 18F-AcOF was bubbled into BPA in trifluoroacetic acid, then purified by high-performance liquid chromatography, and further composited with fructose to afford 18F-FBPA-Fr. Male Fischer 344 rats bearing F98 glioma in the left brain were used for biologic studies. The biodistribution of BPA-Fr and 18F-FBPA-Fr was determined, and the microautoradiography and PET imaging of 18F-FBPA-Fr were performed, on the 13th day after tumor inoculation. Results: The radiochemical purity of 18F-FBPA-Fr was >97% and the radiochemical yield of 18F-FBPA-Fr was 20%-25%. In glioma-bearing rats, the accumulation ratios of B-10 for glioma-to-normal brain were 2.05, 1.86, 1.24, and 1.10 at 0.5, 1, 2, and 4 h, respectively, after administration of 43 mg BPA-Fr via the tail vein. The accumulation ratios of 18F-FBPA-Fr for glioma-to-normal brain were 3.45, 3.13, 2.61, and 2.02, whereas the tumor-to-heart blood ratios were 1.72, 2.61, 2.00, and 1.93, respectively, for the same time points. The uptake characteristics of BPA-Fr and 18F-FBPA-Fr in F98 glioma were similar with a maximum at 1 h after the drugs' administration. The results obtained from the biodistribution studies indicated that 0.5-1 h after BPA-Fr injection would be the optimal time for BNCT. Biodistribution, PET images, and brain microautoradiography of 18F-FBPA-Fr all confirmed this finding. Conclusion: 18F-FBPA-Fr showed specific tumor uptake in F98 glioma-bearing rats and could be used as a probe for BPA-Fr in BNCT. This study provides useful information for the future clinical application of BNCT in brain tumor therapy.
|頁（從 - 到）||302-308|
|期刊||Journal of Nuclear Medicine|
|出版狀態||已發佈 - 二月 1 2004|
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