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^99mTc- and ¹¹¹In-Labeled -Melanocyte-Stimulating Hormone Peptides as Imaging Probes for Primary and Pulmonary Metastatic Melanoma Detection

¹ College of Pharmacy, University of New Mexico, Albuquerque, New Mexico; ² Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri; ³ Department of Radiology, University of Missouri-Columbia, Columbia, Missouri; and ⁴ Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri

Correspondence: For correspondence or reprints contact: Thomas P. Quinn, PhD, 117 Schweitzer Hall, Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211. E-mail: quinnt{at}missouri.edu

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 ^99mTc- and ¹¹¹In-labeled -melanocyte-stimulating hormone (-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-Phe⁷,Arg¹¹]-MSH_3–13 [(Arg¹¹)CCMSH] and [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]Re(Arg¹¹)CCMSH [DOTA-Re(Arg¹¹)CCMSH] were labeled with ^99mTc and ¹¹¹In. The pharmacokinetics of ^99mTc-(Arg¹¹)CCMSH were examined in B16/F1 flank and B16/F10 pulmonary metastatic murine melanoma-bearing C57 mice. The biodistribution of ¹¹¹In-DOTA-Re(Arg¹¹)CCMSH was performed in B16/F10 pulmonary metastatic murine melanoma-bearing C57 mice. SPECT/CT of ^99mTc-(Arg¹¹)CCMSH and ¹¹¹In-DOTA-Re(Arg¹¹)CCMSH was determined in B16/F1 flank and B16/F10 pulmonary metastatic murine melanoma-bearing C57 mice. Results: ^99mTc-(Arg¹¹)CCMSH and ¹¹¹In-DOTA-Re(Arg¹¹)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 ^99mTc-(Arg¹¹)CCMSH or ¹¹¹In-DOTA-Re(Arg¹¹)CCMSH as the imaging probe. ^99mTc-(Arg¹¹)CCMSH exhibited images with greater resolution of metastatic melanoma lesions compared with ¹¹¹In-DOTA-Re(Arg¹¹)CCMSH. Conclusion: The favorable tumor imaging properties of ^99mTc-(Arg¹¹)CCMSH and ¹¹¹In-DOTA-Re(Arg¹¹)CCMSH highlighted their potential as novel probes for primary and metastatic melanoma detection.

Key Words: -melanocyte-stimulating hormone • ^99mTc- and ¹¹¹In-labeled peptides • primary and metastatic melanoma detection

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