Objective
The work concerns the synthesis of novel boron compounds with potential for application in medicine (in particular Boron Neutron Capture Therapy), and a study of biological properties such as toxicity, biodistribution, and pharma-cokinetics using animal models for selected compounds. This will lead to first stage clinical studies in humans. It requires the collaboration of synthetic laboratories, biological laboratories, nuclear analytical laboratories, and clinical departments. The synthetic work is to be carried out by the groups of Brattsev, Kuznetsov, and Zakharkin in Russia, and derivatives of [B12H12]2-, C2B10H12, [C2B9H12]-, and [CB11H12]-. These boron cages will be attached to biologically active tumour-seeking stituents, and will also be radiolabelled for animal distribution studies. The biological species to which the boron cages are coupled include sulfur-containing groups {SCN, SC(NH2)2}, porphyrins, phthalocyanines, rhodamine, aminoacids, ether lipids, nitrogen heterocycles, and phosphorus compounds. The biological work and analysis of tissue samples for boron content will be carried out by the groups of Spryshkova, Oulianenko and Borisov. Spryshkova and Borisov will examine synthesised compounds to determine:
acute toxicity in small animals,
cytotoxicity for tumour cells, and
pharmaco- kinetic properties in different tissues of two tumour models,
using prompt gamma-ray neutron activation analysis for boron determination. Gabel will study intracellular distribution by EELS. Oulianenko will investigate the distribution in tumour bearing animals using radioiodine labelled compounds, and commence clinical studies in patients.
Topic(s)
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G1 1XL Glasgow
United Kingdom