Uptake of two 10B-compounds in liver metastases of colorectal adenocarcinoma for extracorporeal irradiation with boron neutron capture therapy (EORTC trial 11001)

Disseminated metastases of colorectal cancer in liver are incurable. The trial EORTC 11001 investigates whether autotransplantation after extracorporeal irradiation of the liver by boron neutron capture therapy (BNCT) might become a curative treatment option because of selective uptake of the compounds sodium mercaptoundecahydro-closo-dodecaborate (BSH) or L-para-boronophenylalanine (BPA). BSH (50 mg/kg bw) or BPA (100 mg/kg bw) were infused into patients who subsequently underwent resection of hepatic metastases. Blood and tissue samples were analyzed for the B-10-concentration with prompt gamma ray spectroscopy (PGRS). Three patients received BSH and 3 received BPA. Adverse effects from the boron carriers did not occur. For BSH, the highest B-10-concentration was observed in liver (31.5 +/- 2.7 mu g/g) followed by blood (24.8 +/- 4.7 mu g/g) and tumor (23.2 +/- 2.1 mu g/g) with a mean B-10-concentration ratio metastasis/liver of 0.72 +/- 0.07. For BPA, the highest B-10-concentration was measured in metastases (12.1 +/- 2.2 mu g/g) followed by liver (8.5 +/- 0.5 mu g/g) and blood (5.8 +/- 0.8 mu g/g). As BPA is transported actively into cells, viable, metabolically active cells accumulate exclusively this compound. Consequently, a model is proposed to adjust the values measured by PGRS for the proportion of viable cells to express the relevant B-10-concentration in the tumor cells, revealing a B-10-concentration ratio metastasis/liver of 6.8 +/- 1.7. In conclusion, BSH is not suitable as B-10-carrier in liver metastases as the B-10-concentration in liver was higher compared to metastasis. BPA accumulates in hepatic metastases to an extent that allows for extracorporeal irradiation of the liver with BNCT. (C) 2007 Wiley-Liss, Inc.