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Evaluation of Pharmacokinetics of 4-Borono-2-¹⁸F-Fluoro-L-Phenylalanine for Boron Neutron Capture Therapy in a Glioma-Bearing Rat Model with Hyperosmolar Blood–Brain Barrier Disruption

¹ Institute of Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
² Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan
³ Institute of Radiological Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan
⁴ Deprtment of Medicine, National Yang-Ming University, Taipei, Taiwan
⁵ Department of Engineering and System Science, National Tsing Hua University, Hsinchu, Taiwan

View larger version (22K): [in a new window]   FIGURE 1. Pharmacokinetics of 18F-FBPA for F98 glioma-bearing rats determined by PET. (A) Time–activity curves of 18F-FBPA in tumors and ipsilateral brains of F98 glioma-bearing rats derived from dynamic PET images after intracarotid (i.c.) injection with and without BBB-D and after intravenous (i.v.) injection. (B) Tumor-to-ipsilateral brain ratio of 18F-FBPA.

View larger version (14K): [in a new window]   FIGURE 2. Time–activity curves of 18F-FBPA in blood of F98 glioma-bearing Fischer 344 rats after intracarotid (i.c.) injection with and without BBB-D. Data points were fitted with open 2-compartment model (Cp = Ae–t + Be–ßt). r2 = 0.97–0.99.

View larger version (13K): [in a new window]   FIGURE 3. Biodistribution of 10B-BPA for F98 glioma-bearing rats. (A) Boron concentration in tumor, ipsilateral brain, contralateral brain, and blood of F98 glioma-bearing Fischer 344 rats after intracarotid injection of BPA (300 mg/kg) with BBB-D. (B) Tumor-to-normal tissue ratio of boron concentration. Rats were under ketamine mixture anesthesia.

View larger version (15K): [in a new window]   FIGURE 4. Boron concentration in tumor, ipsilateral brain (IB), contralateral brain (CB), and blood at 2.5 h after administration of 500 mg/kg of BW of BPA under isoflurane/ketamine mixture anesthesia.

View larger version (8K): [in a new window]   FIGURE 5. Correlation among tumor region of interest (ROI), k12/k21, and tumor-to-ipsilateral brain ratio. (A) Correlation between radioactivity of tumor ROI and k12/k21. (B) Correlation between tumor-to-ipsilateral brain ratio and k12/k21. Each point represents one rat. Radioactivity of tumor ROI and tumor-to-ipsilateral brain ratio were derived from PET images at 2.5 h after intracarotid injection of 18F-FBPA with and without BBB-D. k12/k21 ratio was obtained from pharmacokinetic analysis of blood of the same rat.