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Uptake of two 10 B‐compounds in liver metastases of colorectal adenocarcinoma for extracorporeal irradiation with boron neutron capture therapy (EORTC Trial 11001)
Author(s) -
Wittig Andrea,
Malago Massimo,
Collette Laurence,
Huiskamp René,
Bührmann Sandra,
Nievaart Victor,
Kaiser Gernot M.,
Jöckel KarlHeinz,
Schmid Kurt Werner,
Ortmann Uta,
Sauerwein Wolfgang A.
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23224
Subject(s) - extracorporeal , medicine , metastasis , colorectal cancer , gastroenterology , boron , cancer , nuclear medicine , urology , chemistry , organic chemistry
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 forthe 10 B‐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 10 B‐concentration was observed in liver (31.5 ± 2.7 μg/g) followed by blood (24.8 ± 4.7 μg/g) and tumor (23.2 ± 2.1 μg/g) with a mean 10 B‐concentration ratio metastasis/liver of 0.72 ± 0.07. For BPA, the highest 10 B‐concentration was measured in metastases (12.1 ± 2.2 μg/g) followed by liver (8.5 ± 0.5 μg/g) and blood (5.8 ± 0.8 μg/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 10 B‐concentration in the tumor cells, revealing a 10 B‐concentration ratio metastasis/liver of 6.8 ± 1.7. In conclusion, BSH is not suitable as 10 B‐carrier in liver metastases as the 10 B‐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. © 2007 Wiley‐Liss, Inc.