Melanoma is a
malignancy with increasing incidence. Although primary
tumors that are localized to the skin can be successfully treated by surgical removal, there is no satisfactory treatment for metastatic
melanoma, a condition that has currently an estimated 5-year survival of just 6%. During the last decade, β- or α-emitter-radiolabeled
peptides that bind to different receptors on a variety of
tumors have been investigated as potential therapeutic agents in both the preclinical and clinical settings with encouraging results. A recent study demonstrated that 188-Rhenium ((188)Re)-labeled, via
HYNIC ligand, fungal
melanin-binding decapeptide 4B4 was effective against experimental MNT1 human
melanoma and was safe to normal melanized tissues. The availability of radiolanthanides with diverse nuclear emission schemes and half-lives provides an opportunity to expand the repertoire of
peptides for
radionuclide therapy of
melanoma. The
melanin-binding decapeptide 4B4 was radiolabeled with (177)Lu, (166)Ho, and (153)Sm via a DO3A chelate. The stability studies of Ln*-DO3A-4B4 in
phosphate-buffered saline, serum, and a
hydroxyapatite assay demonstrated that (177)Lu-labeled
peptide was more stable than (166)Ho- and (153)Sm-labeled
peptides, most likely because of the smallest ionic radius of the former allowing for better complexation with DO3A. Binding of Ln*-DO3A-4B4 to the lysed highly melanized MNT1
melanoma cells demonstrated the specificity of
peptides binding to
melanin. In vivo biodistribution data for (177)Lu-DO3A-4B4 given by intraperitoneal administration to lightly pigmented human metastatic A2058
melanoma-bearing mice demonstrated very high uptake in the kidneys and low
tumor uptake.
Intravenous administration did not improve the
tumor uptake. The plausible explanation of low
tumor uptake of (177)Lu-DO3A-4B4 could be its decreased ability to bind to
melanin during in vitro binding studies in comparison with (188)Re-HYNIC-4B4, exacerbated by the very fast clearance from the blood and the kidneys "sink" effect.