99mTc- and 111In-labeled Alpha-melanocyte-stimulating Hormone Peptides As Imaging Probes for Primary and Pulmonary Metastatic Melanoma Detection

Unlabelled: It is highly desired to develop new imaging probes for early detection of melanoma as early diagnosis and prompt surgical removal are a patient's best hope for a cure. The purpose of this study was to determine whether (99m)Tc- and (111)In-labeled alpha-melanocyte-stimulating hormone (alpha-MSH) peptides could be used as imaging probes for primary and metastatic melanoma using dual-modality micro-SPECT/CT detection.

Methods: [Cys(3,4,10),d-Phe(7),Arg(11)]alpha-MSH(3-13) [(Arg(11))CCMSH] and [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]Re(Arg(11))CCMSH [DOTA-Re(Arg(11))CCMSH] were labeled with (99m)Tc and (111)In. The pharmacokinetics of (99m)Tc-(Arg(11))CCMSH were examined in B16/F1 flank and B16/F10 pulmonary metastatic murine melanoma-bearing C57 mice. The biodistribution of (111)In-DOTA-Re(Arg(11))CCMSH was performed in B16/F10 pulmonary metastatic murine melanoma-bearing C57 mice. SPECT/CT of (99m)Tc-(Arg(11))CCMSH and (111)In-DOTA-Re(Arg(11))CCMSH was determined in B16/F1 flank and B16/F10 pulmonary metastatic murine melanoma-bearing C57 mice.

Results: (99m)Tc-(Arg(11))CCMSH and (111)In-DOTA-Re(Arg(11))CCMSH exhibited high tumor uptakes (14.03 +/- 2.58 percentage injected dose/gram [%ID/g] at 1 h after injection and 17.29 +/- 2.49 %ID/g at 2 h after injection) in B16/F1 melanoma-bearing mice, and the flank melanoma tumors were clearly imaged by micro-SPECT/CT. Nontarget organ uptakes were considerably lower except for the kidneys. B16/F10 pulmonary melanoma metastases were also clearly visualized by micro-SPECT/CT using (99m)Tc-(Arg(11))CCMSH or (111)In-DOTA-Re(Arg(11))CCMSH as the imaging probe. (99m)Tc-(Arg(11))CCMSH exhibited images with greater resolution of metastatic melanoma lesions compared with (111)In-DOTA-Re(Arg(11))CCMSH.

Conclusion: The favorable tumor imaging properties of (99m)Tc-(Arg(11))CCMSH and (111)In-DOTA-Re(Arg(11))CCMSH highlighted their potential as novel probes for primary and metastatic melanoma detection.