Disposition and tissue distribution of boron after infusion of borocaptate sodium in patients with malignant brain tumors.

Abstract

PURPOSE:

In the frame of the Czech boron neutron capture therapy (BNCT) project, a clinical Phase I study of borocaptate sodium [Na2B12H11SH (BSH)] as the boron-10 delivery agent was performed to obtain data on disposition and tissue distribution of boron after an infusion of this compound, as well as to establish an optimal protocol for BNCT of malignant cerebral tumors.

METHODS AND MATERIALS:

The kinetics of boron disposition after an infusion of borocaptate sodium (25 mg/kg body wt over the period of 1 h) was studied in a group of 10 patients with astrocytoma or glioblastoma of cerebral hemispheres using a modification of the Soloway-Messer colorimetric method. The boron content of tissues (tumor, healthy brain, dura mater, muscle, skin, and cranial bone) removed during the operation performed with latencies varying between 3 and 18 h was investigated by atomic emission spectrometry.

RESULTS:

Compartmental analysis of boron blood concentrations has shown that in the majority of patients (four males and three females), the concentration decline can be adequately described by a two-compartment pharmacokinetic model (i.e., by a biexponential relationship). The calculated half-lives of the initial (fast) phase of the concentration decline varied between 0.85 and 3.65 h, whereas the half-life values for the terminal (slow) phase ranged between 22.2 and 111.8 h. However, in the remaining three patients (all females), the goodness of fit of the boron concentration data was significantly better when a pharmacokinetic model with three compartments was assumed. In these patients, therefore, an additional ultrafast phase with a half-life varying between 17 and 37 min was detected in the beginning of the boron blood concentration decline. On the other hand, in one of these patients, the half-life of the terminal phase was found to be 415 h (i.e., more than 17 days). Such a long persistence in the body is explained by the very high value of the total distribution volume, indicating extensive binding of BSH in peripheral tissues. Another reason may be enterohepatic recycling of BSH.

CONCLUSION:

Tumor-to-blood ratios higher than 1.5, which are necessary for an effective outcome of BNCT, can be obtained only if the time interval elapsing between the onset of surgery and termination of BSH infusion is at least 12 h.

• Authors: V Horn, J Slánský, I Janku, O Strouf, K Sourek, F Tovarys
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 41 Issue 3 Pg. 631-8 (Jun 01 1998) ISSN: 0360-3016 [Print] United States
• PMID: 9635713 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

• Borohydrides
• Sulfhydryl Compounds
• mercaptoundecahydrododecaborate
• Boron

Topics

• Adult
• Borohydrides (adverse effects, therapeutic use)
• Boron (blood, pharmacokinetics)
• Boron Neutron Capture Therapy (standards)
• Female
• Half-Life
• Humans
• Male
• Middle Aged
• Sulfhydryl Compounds (adverse effects, therapeutic use)
• Tissue Distribution