alexa Radioimmunoconjugates for targeted alpha therapy of malignant melanoma.
Social & Political Sciences

Social & Political Sciences


Author(s): Abbas Rizvi SM, Sarkar S, Goozee G, Allen BJ

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Abstract Effective targeted cancer therapy requires high selectivity and cytotoxicity. To this end we have prepared and tested a new alpha-emitting radioimmunoconjugate (RIC) against malignant melanoma. The melanoma antibody 9.2.27 is specific for most melanoma cell lines. This antibody was labelled with an a emitter, bismuth-213 (213Bi), and a positron emitter, terbium-152 (152Tb), which is an analogue of the alpha-emitting radioisotope terbium-149. The chelators cDTPAa (a cyclic anhydride of diethylenetriamine pentacetic acid) and CHX-A" (a 2-(p-SCN-Bz)-cyclohexyl-DTPA ligand) were used in order to obtain high labelling yields for both isotopes with either chelator. The labelling efficiency with 213Bi was found to be 96\% and 92\% with cDTPAa and CHX-A", respectively. With 152Tb it was 93\% and 89\%, respectively. Serum stability studies showed 20\% leaching with 213Bi over a period of 2.5 half-lives. For 152Tb the leaching was 13\%. There was no difference in the melanoma cell binding of the labelled and unlabelled antibodies. DNA synthesis data were compared for both isotopes with either chelator. Based on these results, the therapeutic activity ratio for 213Bi a particles and 152Tb positrons for the same endpoint was calculated to be 120. The stability of the bismuth and terbium RICs, together with the outstanding cytotoxicity of the alpha emitter, provides the basis for a new approach to the potential control of micrometastatic melanoma.
This article was published in Melanoma Res and referenced in Anthropology

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