Metastatic melanoma imaging with an ¹¹¹In-labeled lactam bridge-cyclized α-melanocyte-stimulating hormone peptide

Introduction: The purpose of this study was to examine whether a novel lactam bridge-cyclized ¹¹¹In-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Gly-Glu-c[Lys-Nle-Glu-His-d-Phe-Arg-Trp-Gly-Arg-Pro-Val-Asp] {DOTA-GlyGlu-CycMSH} could be an effective imaging probe for metastatic melanoma detection. Methods: ¹¹¹In-DOTA-GlyGlu-CycMSH was prepared and purified by reverse-phase high-performance liquid chromatography (RP-HPLC). The internalization and efflux of ¹¹¹In-DOTA-GlyGlu-CycMSH were examined in B16/F10 melanoma cells. The biodistribution of ¹¹¹In-DOTA-GlyGlu-CycMSH was determined in B16/F10 pulmonary metastatic melanoma-bearing and normal C57 mice. Pulmonary metastatic melanoma imaging was performed by small-animal single-photon emission computed tomography (SPECT)/CT (Nano-SPECT/CT) using ¹¹¹In-DOTA-GlyGlu-CycMSH as an imaging probe and compared with 2-[¹⁸F]fluoro-2-deoxy-d-glucose ([¹⁸F]FDG) positron emission tomography (PET) imaging. Results: ¹¹¹In-DOTA-GlyGlu-CycMSH was readily prepared with greater than 95% radiolabeling yield. ¹¹¹In-DOTA-GlyGlu-CycMSH displayed rapid internalization and extended efflux in B16/F10 cells. ¹¹¹In-DOTA-GlyGlu-CycMSH exhibited significantly (P<.05) higher uptakes (2.00±0.74%ID/g at 2 h post-injection and 1.83±0.12%ID/g at 4 h post-injection) in metastatic melanoma-bearing lung than that in normal lung (0.08±0.08%ID/g and 0.05±0.05%ID/g at 2 and 4 h post-injection, respectively). The activity accumulation in normal organs was low (<0.5%ID/g) except for the kidneys 2 and 4 h post-injection. B16/F10 pulmonary melanoma metastases were clearly visualized with ¹¹¹In-DOTA-GlyGlu-CycMSH 2 h post-injection rather than with [¹⁸F]FDG 1 h post-injection. Conclusions: ¹¹¹In-DOTA-GlyGlu-CycMSH exhibited favorable metastatic melanoma-targeting and -imaging properties, highlighting its potential as an effective imaging probe for metastatic melanoma detection.