sup 203^Pb-Labeled [alpha]-Melanocyte-Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection

Peptide-targeted α-therapy with 7.4 MBq of ^sup 212^Pb-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-ReO-[Cys^sup 3,4,10^, D-Phe^sup 7^,Arg^sup 11^]α-MSH^sub 3-13^ (^sup 212^Pb-DOTA-Re(Arg^sup 11^)CCMSH) cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-d study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient-specific dosimetry and to monitor the tumor response to ^sup 212^Pb-DOTA-Re(Arg^sup 11^)CCMSH therapy. The purpose of this study was to evaluate the potential of ^sup 203^Pb-DOTA-Re(Arg^sup 11^)CCMSH as a matched-pair SPECT agent for ^sup 212^Pb-DOTA-Re(Arg^sup 11^) CCMSH. Methods: DOTA-Re(Arg^sup 11^)CCMSH was labeled with ^sup 203^Pb in 0.5 M NH^sub 4^OAc buffer at pH 5.4. The internalization and efflux of ^sup 203^Pb-DOTA-Re(Arg^sup 11^)CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of ^sup 203^Pb-DOTA-Re(Arg^sup 11^)CCMSH was examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT study was performed with ^sup 203^Pb-DOTA-Re(Arg^sup 11^)CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h after injection. Results: ^sup 203^Pb-DOTA-Re(Arg^sup 11^)CCMSH was easily prepared in NH^sub 4^OAc buffer and completely separated from the excess nonradiolabeled peptide by reversed-phase high-performance liquid chromatography (RP-HPLC). ^sup 203^Pb-DOTA-Re(Arg^sup 11^)CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of ^sup 203^Pb-DOTA-Re(Arg^sup 11^)CCMSH activity internalized after a 20-min incubation at 25°C. After incubation of the cells in culture medium for 20 min, 78% of internalized activity remained in the cells. ^sup 203^Pb-DOTA-Re(Arg^sup 11^)CCMSH exhibited a biodistribution pattern similar to that of ^sup 212^Pb-DOTA-Re(Arg^sup 11^)CCMSH in B16/ F1 melanoma-bearing mice. ^sup 203^Pb-DOTA-Re(Arg^sup 11^)CCMSH exhibited a peak tumor uptake of 12.00 ± 3.20 percentage injected dose per gram (%ID/g) at 1 h after injection. The tumor uptake gradually decreased to 3.43 ± 1.12 %ID/g at 48 h after injection. ^sup 203^Pb-DOTA-Re(Arg^sup 11^)CCMSH exhibited a peak tumor-to-kidney uptake ratio of 1.53 at 2 h after injection. The absorbed doses to the tumor and kidneys were 4.32 and 4.35 Gy, respectively, per 37 MBq. Whole-body clearance of ^sup 203^Pb-DOTA-Re(Arg^sup 11^)CCMSH was fast, with approximately 89% of the injected activity cleared through the urinary system by 2 h after injection. ^su