title: Uptake of two 10B-compounds in liver metastases of colorectal adenocarcinoma for extracorporeal irradiation with boron neutron capture therapy (EORTC Trial 11001).
abstract: 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 microg/g) followed by blood (24.8 +/- 4.7 microg/g) and tumor (23.2 +/- 2.1 microg/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 microg/g) followed by liver (8.5 +/- 0.5 microg/g) and blood (5.8 +/- 0.8 microg/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.
authors.affiliation: Department of Radiation Oncology, University Duisburg-Essen, Essen, Germany. andrea.wittig@uni-due.de
authors.forename: Andrea
authors.initials: A
authors.lastname: Wittig
authors.forename: Massimo
authors.initials: M
authors.lastname: Malago
authors.forename: Laurence
authors.initials: L
authors.lastname: Collette
authors.forename: René
authors.initials: R
authors.lastname: Huiskamp
authors.forename: Sandra
authors.initials: S
authors.lastname: Bührmann
authors.forename: Victor
authors.initials: V
authors.lastname: Nievaart
authors.forename: Gernot M
authors.initials: GM
authors.lastname: Kaiser
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.forename: Kurt Werner
authors.initials: KW
authors.lastname: Schmid
authors.forename: Uta
authors.initials: U
authors.lastname: Ortmann
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Sauerwein
mesh_terms: D000230:Adenocarcinoma / Q000532:radiotherapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D001896:Boron Compounds / Q000032:analysis / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D014182:Transplantation, Autologous
chemical_list: D001896:Boron Compounds; C119788:dodecaborate; D010649:Phenylalanine; C033685:4-boronophenylalanine