Preparation and in vivo evaluation of linkers for 211At labeling of humanized anti-Tac.

Autor: Yordanov AT; Radiation Oncology Branch, Division of Clinical Sciences, National Cancer Institute, Department of Nuclear Medicine, Bethesda, MD 20892, USA., Garmestani K, Zhang M, Zhang Z, Yao Z, Phillips KE, Herring B, Horak E, Beitzel MP, Schwarz UP, Gansow OA, Plascjak PS, Eckelman WC, Waldmann TA, Brechbiel MW
Jazyk: angličtina
Zdroj: Nuclear medicine and biology [Nucl Med Biol] 2001 Oct; Vol. 28 (7), pp. 845-56.
DOI: 10.1016/s0969-8051(01)00257-8
Abstrakt: The syntheses, radiolabeling, antibody conjugation, and in vivo evaluation of new linkers for 211At labeling of humanized anti-Tac (Hu-anti-Tac), an antibody to the alpha-chain of the IL-2 receptor (IL-2Ralpha) shown to be a useful target for radioimmunotherapy are described. Synthesis of the organometallic linker precursors is accomplished by reaction of the corresponding bromo- or iodoaryl esters with bis(tributyltin) in the presence of a palladium catalyst. Subsequent conversion to the corresponding N-succinimidyl ester and labeling with 211At of two new linkers, N-succinimidyl 4-[211At]astato-3-methylbenzoate and N-succinimidyl N-(4-[211At]astatophenethyl)succinamate (SAPS), together with the previously reported N-succinimidyl 4-[211At]astatobenzoate and N-succinimidyl 3-[211At]astato-4-methylbenzoate, are each conjugated to Hu-anti-Tac. The plasma survival times of these conjugates are compared to those of directly iodinated (125I) Hu-anti-Tac. The N-succinimidyl N-(4-[211At]astatophenethyl)succinamate compound (SAPS) emerged from this assay as the most viable candidate for 211At-labeling of Hu-anti-Tac. SAPS, along with the directly analogous radio-iodinated reagent, N-succinimidyl N-(4-[125I]astatophenethyl)succinamate (SIPS), are evaluated in a biodistribution study along with directly iodinated (125I) Hu-anti-Tac. Blood clearance and biological accretion results indicate that SAPS is a viable candidate for further evaluation for radioimmunotherapy of cancer.
Databáze: MEDLINE
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