99mTc- and 111In-labeled alpha-melanocyte-stimulating hormone peptides as imaging probes for primary and pulmonary metastatic melanoma detection.
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.


CONCLUSIONS
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.
Miao
Yubin
Y
College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USA.
Benwell
Katherine
K
Quinn
Thomas P
TP
D000818:Animals; D045744:Cell Line, Tumor; D007205:Indium Radioisotopes; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D008545:Melanoma / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008956:Models, Chemical; D009362:Neoplasm Metastasis; D010455:Peptides / Q000737:chemistry*; D013667:Technetium; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D000521:alpha-MSH / Q000378:metabolism*
D007205:Indium Radioisotopes; D010455:Peptides; D000521:alpha-MSH; D013667:Technetium