Applications of radiolabeled boron clusters to the diagnosis and treatment of cancer

The aforementioned studies reveal that boron cluster anion derivatives can be successfully employed as carrier systems for radioiodine, astatine, tritium, and radiocobalt. The radioiodination of the targeted boron cluster anions is simple and provides stable radiolabeled products that are attractive due to the enhanced stability of the B-I bond with respect to in vivo dehalogenation. This appreciable in vivo stability can be attributed to the inorganic nature of the boron clusters and their apparent invisibility to enzyme systems responsible for dehalogenation. The conjugation of boron cluster derivatives to biomolecules, such as antibodies and growth factors, is possible using standard conjugation techniques. A general problem with the performance of all these conjugates is the increased liver uptake and decreased tumor uptake relative to the native antibody. The undesired liver uptake becomes significant as the number of boron cluster derivatives attached to the tumor-targeting molecule is increased. It remains questionable whether it will be possible to deliver the large amounts of boron required for BNCT to tumor cells employing this methodology. On the other hand, the conjugation of just one boron cage to the investigated antibodies did not lead to alteration of their in vivo properties. This observation is important and indicates that radiolabeled boron cluster immunoconjugates can be used as excellent tumor-imaging agents (method 3 in Scheme 4). This could be demonstrated in the case of the Venus flytrap complex with 57Co, which is probably the most stable π-complex of cobalt known today. Currently under investigation are the clinically important positron-emitting 55Co isotope and other radiometals, such as 99mTc, complexed by the Venus flytrap. Effective tumor-imaging and radioimmunotherapy require the boron cluster to be radiolabeled prior to its conjugation to the immunoprotein. This is exemplified in the cases of radioiodination and astatination by method 3 in Scheme 4, since only by employing this strategy will the radiohalogen be exclusively placed on the boron cage.