Medical Applications of Gadolinium and/or Boron-Labeled Pharmaceuticals

Abstract

Boron neutron capture therapy (BNCT) is a binary treatment modality that can selectively irradiate tumor tissue. The key to effective BNCT is the preferential accumulation of 10 B in the tumor relative to the surrounding normal tissues. A screening procedure was developed under this CRADA that is an improvement over previously reported techniques. This method was used to evaluate the two compounds produced by BBI, the amino acid p-boronophenylalanine (BPA)and the sulfhydryl boroane N 2 B 12 H 11 SH (BSH), for clinically useful accumulation in a panel of human tumor cell lines. BPA showed selective accumulation in: squamous cell carcinoma of the lung; small cell carcinoma of the lung; osteosarcoma; prostate carcinoma; and ovarian carcinoma. Of these it was decided to pursue application of BPA-based BNCT to lung tumors. BPA distribution in nude mice bearing subcutaneous human lung tumor xenografts showed very favorable results. At 3 hours post-injection, the tumor/blood boron concentration ratio was 5:1, the tumorflung ratio was 6:1. The treatment planning sofiware, already in use for the glioblastoma BNCT clinical trial underway at BNL, was used for simulation of a human lung tumor treatment using BNCT. Input data for this simulation included the nude mouse biodistribution data, human lung tumor CT geometry, and the same assumptions about relative biological effectiveness of the BNCT dose components currently in use for the human brain tumor trial. The results of this lung tumor simulation indicate significant sparing of normal lung compared to tumor. We conclude that the BBI product BPA has potential applications in BNCT of other tumor sites. BPA-based BNCT for human small cell carcinoma of the lung looks promising. Further studies into the radiation biology of the normal lung will be required prior to clinical BNCT for lung tumors.