In vivo evaluation of 99mTc/188Re-labeled linear alpha-melanocyte stimulating hormone analogs for specific melanoma targeting

Radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) analogs were examined in melanoma bearing mice to determine the effects of peptide length, structure, and radiometal chelation chemistry on tumor targeting and in vivo biodistribution. The linear alpha-MSH analogs [Nle(4), D-Phe(7)]alpha-MSH (NDPMSH) and [D-Phe(7)]alpha-MSH5-10 (DPMSH) were radiolabeled with Tc-99m and Re-188 via the addition of tetrafluorophenyl mercapto-acetylglycylglycyl-gamma-aminob (MAG(2)) or tetrapeptide Ac-Cys-Gly-Cys-Gly (CGCG) chelation moieties. I-125-Tyr(2)-NDPMSH was obtained by direct iodination of the Tyr(2) residue. Tumor uptake of Tc-99m-labeled CGCG- and MAG(2)-NDPMSH analogs at 30 min postinjection were 6.52 +/- 1.11 %ID/g and 4.17 +/- 1.34 %ID/g, respectively, resulting in a significantly higher tumor-to-blood uptake ratio than that of I-125-NDPMSH or a shorter alpha-MSH analog, Tc-99m-CGCG DPMSH. The combination of radiolabeling efficacy and in vivo tumor uptake highlights the potential of Tc-99m-CGCG-NDPMSH as a melanoma imaging agent. NUCL MED BIOL 26;6:687-693, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.