Evaluation of fluorine-18-BPA-fructose for boron neutron capture treatment planning

Boron neutron capture therapy (BNCT) using 4-[10B]boronophenylalanine-fructose (BPA-Fr) is in Phase II clinical trials to validate BNCT as a treatment for glioblastoma multiforme and melanoma. Successful BNCT depends on knowledge of the distribution of boron-containing agents in both tumor and normal tissue as currently determined by chemical confirmation of boron deposition in surgically removed malignant tissue before BNCT.

We used PET to noninvasively obtain in vivo information on the pharmacokinetics of the 18F-labeled analog of BPA-Fr in two patients with glioblastoma multiforme. Time-activity curves generated from the bolus injection of 18F-BPA-Fr were coinvolved to simulate a continuous infusion used for BNCT therapy.

Distribution of 18F-BPA-Fr by PET was found to be consistent with tumor as identified by MR imaging. The 18F-BPA-Fr tumor-to-normal brain uptake ratio was 1.9 in Patient 1 and 3.1 in Patient 2 at 52 min after injection. The 18F-BPA-Fr uptake ratio in glioblastoma paralleled that of nonlabeled BPA-Fr seen in patients as previously determined by boron analysis of human glioblastoma tissue obtained from pre-BNCT surgical biopsy.

Knowledge of the biodistribution of BPA-Fr enables pre-BNCT calculation of expected tissue dosimetry for a selected dose of BPA-Fr at a specific neutron exposure. Fluorine-18-BPA-Fr PET is capable of providing in vivo BPA-Fr biodistribution data that may prove valuable for patient selection and pre-BNCT treatment planning.