Biodistribution of Boron Sulfhydryl for Boron Neutron Capture Therapy in Patients with Intracranial Tumors

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Abstract
THE BIODISTRIBUTION OF boron sulfhydryl (BSH) was evaluated for boron neutron capture therapy of brain tumors. A selective boron delivery to the neoplasm is a prerequisite for successful therapy. The uptake of BSH after intravenous administration was analyzed in neoplastic and normal tissues in 61 patients undergoing craniotomies for intracranial tumors. The patients received 10 to 100 mg of BSH/kg (5–50 mg of 10B/kg) body weight, 2 to 72 hours before surgery. The tumor boron concentrations ranged from 0.2 ppm (μg/g) in a low-grade glioma to 19.5 ppm in a high-grade glioma. The tumor to blood boron ratio rose above 1 in 15 of 24 high-grade intracerebral tumors, 18 h or more after BSH infusion. The boron concentration in high-grade tumors was heterogeneous. Low-grade intracerebral tumors showed a low boron concentration with a tumor to blood ratio below 1. Extracerebral tumors, mainly meningiomas, showed boron concentrations comparable with high-grade tumors, with a tumor to blood ratio above 1 in 10 of 17 patients. The boron concentrations in skin and muscle compared roughly with the blood values. Boron did not enter normal brain in any significant amount. In high-grade tumors, tumor to brain ratios were above 2. Low boron concentrations in normal brain make BSH safe for a Phase I normal tissue tolerance study. Computed tomographic contrast enhancement was evaluated to tumor boron uptake for 30 patients. Tumor enhancement on computed tomography does not permit the prediction of individual tumor boron concentrations; however, the absence of a contrast enhancement was always associated with low boron uptake.