Theranostic Radiotracers for Melanoma Imaging and Therapy: A Comparative Study of Subcutaneous and Intradermal Tumor Models Using DOTA-Re-CCMSH Peptides.

Abstract

Introduction: Melanoma, with its aggressive behavior and high metastatic potential, presentssignificant clinical challenges. The melanocortin-1 receptor (MC1R) is apromising target for diagnosis and therapy due to its overexpression inmetastatic melanoma. Methods: This study compares the theranostic potential of DOTARe-CCMSH, labeled with ⁶⁸Ga and ¹⁷⁷Lu, in subcutaneous and intradermalmurine melanoma models over an extended period. Radiolabeling achievedhigh molar activities for both isotopes, enabling precise imaging andtherapeutic applications. Results: PET imaging with [⁶⁸Ga]Ga-DOTA-Re-CCMSH showed specific tumoraccumulation, with a mean uptake of 2.25 ± 0.2% ID/g at 2 hours post-injection,enhanced by gelofusine pre-administration. SPECT imaging with [¹⁷⁷Lu]LuDOTA-Re-CCMSH revealed significant and sustained tumor uptake in bothmodels, with mean values of 21.9 ± 7.98 for subcutaneous and 19.8 ± 5.36 forintradermal tumors at 4 hours post-injection, extending up to 24 hours. Thisstudy tracked the therapeutic radiotracer uptake for up to 7 days post-injection, showing continued retention and tumor specificity, especially in the tumor-tomuscle ratio, which reached 172 at 24 hours. Discussion and Conclusions: Comparative biodistribution analyses highlighted differences between subcutaneous and intradermal models, including distinct peritumoral edemaarrangements. These findings emphasize the value of long-term theranosticstudies in understanding tumor behavior and the efficacy of radiolabeledpeptides in melanoma treatment, advancing personalized oncologyapproaches.