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 for the 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 6 2.7 lg/ g) followed by blood (24.8 6 4.7 lg/g) and tumor (23.2 6 2.1 lg/g) with a mean 10 B-concentration ratio metastasis/liver of 0.72 6 0.07. For BPA, the highest 10 B-concentration was measured in metastases (12.1 6 2.2 lg/g) followed by liver (8.5 6 0.5 lg/g) and blood (5.8 6 0.8 lg/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 Bconcentration ratio metastasis/liver of 6.8 6 1.7. In conclusion, BSH is not suitable as 10 B-carrier in liver metastases as the 10 Bconcentration 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.

Receptor‐Mediated Uptake of Boron‐Rich Neuropeptide Y Analogues for Boron Neutron Capture Therapy

“…After comparing the uptake of these two compounds in liver metastases derived from colorectal cancer, a higher boron concentration in the liver metastases was found after BPA administration than after BSH injection. [16] Hence, the choice of compound does not always depend on the boron content of the molecule and often both compounds are combined. [17] No other boron-delivery agent has reached phase I biodistribution studies to date, even though BSH and BPA efficiencies are not always sufficient.…”

Boron Drug Delivery via Encapsulated Magnetic Nanocomposites: A New Approach for BNCT in Cancer Treatment

“…In addition, there was no evidence of tissue damage in any organs assayed in Figure 4, either in the presence or absence of the external magnetic field. Nonetheless, all these promising results suggest that the delivery system can be potentially applied to the treatment of not only brain tumors, but also for other kinds of cancers through BNCT [8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

“…For example, a Finnish research group recently reported that a patient with recurrent head and neck tumors showed an excellent response to BNCT treatments [7]. Lung and liver tumors have also been investigated as potential candidates for BNCT [8,9]. Selective accumulation of boron in the tumor cells produces a substantial therapy ratio during BNCT.…”

Novel Pharmacological and Magnetic Resonance Strategies to Enhance Boron Neutron Capture Therapy (BNCT) Efficacy in the Clinical Treatment of Malignant Glioma

“…Clinical interest in BNCT has also been focused on high-grade gliomas (Chanana et al, 1999), as well as the treatment of malignant meningiomas (Tamura et al, 2006) and cutaneous melanomas (Mishima & Kondoh, 2000). More recently, interest has been extended to other forms of neoplasms such as head-neck cancers (Kankaanranta et al, 2007), liver (Wittig et al, 2008a) and lung tumours , as well as undifferentiated thyroid cancers (Dagrosa et al, 2007). The treatment is binary and is carried out following two distinct phases.…”