Synthesis and in Vivo Evaluation of [¹²³I]Melanin-Targeted Agents

Abstract

This study reports the synthesis, [(123)I]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [(131)I]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [(123)I]4 (ICF01012). The most favorable compounds ([(123)I]20, [(123)I]23, [(123)I]41, and [(123)I]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [(123)I]20 and [(123)I]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [(123)I]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [(123)I]41 and [(123)I]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [(123)I]53 displays favorable in vivo pharmacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [(131)I] therapeutic evaluation.

PET and SPECT imaging of melanoma: the state of the art

“…These above-mentioned efforts also led to the development of 123 I-MEL037 and 123 I-53 (Fig. 1C, D); while the former demonstrated high and prolonged tumor uptake, the latter was derived from structural modification of 123 I-MEL037 and performed even better than 123 I-ICF01012, as the tumor-to-background uptake ratios of 123 I-53 and 123 I-ICF01012 were 31.9 and 18.5, respectively [41, 42]. While the above probes accumulated at high levels in the eyes and thyroid, radioiodinated iochlonicotinamide and radioiodinated phenylacetamides ( 131 I-IHPA and 131 I-IHPP) had lower uptake in most normal organs and highly specific uptake in the melanotic tumor (Fig.…”

“…(F) MicroSPECT image of C57BL/6 mice bearing B16/F0 melanotic melanoma at 24 h postinjection of approximately 11.1 MBq of 123 I-IHPA, the tumor is indicated by the white arrow. Adapted and modified with permission from references [34, 36, 41, 42, 44].…”