RT Journal Article SR Electronic T1 Evaluation of an 111In-DOTA–Rhenium Cyclized α-MSH Analog: A Novel Cyclic-Peptide Analog with Improved Tumor-Targeting Properties JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1847 OP 1855 VO 42 IS 12 A1 JianQing Chen A1 Zhen Cheng A1 Nellie K. Owen A1 Timothy J. Hoffman A1 Yubin Miao A1 Silvia S. Jurisson A1 Thomas P. Quinn YR 2001 UL http://jnm.snmjournals.org/content/42/12/1847.abstract AB The aim of this study was to examine the effect of rhenium-mediated peptide cyclization on melanoma targeting, biodistribution, and clearance kinetics of the α-melanocyte-stimulating hormone (α-MSH) analog 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) coupled ReO-cyclized [Cys3,4,10,d-Phe7]α-MSH3–13 (DOTA-ReCCMSH). Methods: DOTA-ReCCMSH was compared with its reduced nonmetalated linear homolog, DOTA-CCMSH, and an analog in which rhenium cyclization was replaced by disulfide bond cyclization, DOTA-[Cys4,10,d-Phe7]α-MSH4–13 (CMSH). DOTA was also conjugated to the amino terminus of one of the highest-affinity α-MSH receptor-binding peptides, [Nle4,d-Phe7]α-MSH (NDP), as a linear peptide standard. The DOTA-conjugated α-MSH analogs were radiolabeled with 111In and examined for their in vitro receptor-binding affinity with B16/F1 murine melanoma cells, and their in vivo biodistribution properties were evaluated and compared in melanoma tumor–bearing C57 mice. Results: The tumor uptake values of 111In-DOTA–ReCCMSH were significantly higher than those of the other closely related 111In-DOTA–α-MSH conjugates. Even at 24 h after injection, a comparison of the tumor uptake values for 111In-DOTA-coupled ReCCMSH (4.86 ± 1.52 percentage injected dose [%ID]/g), CCMSH (1.91 ± 0.56 %ID/g), CMSH (3.09 ± 0.32 %ID/g), and NDP (2.47 ± 0.79 %ID/g) highlighted the high tumor retention property of ReCCMSH. Rhenium-coordinated cyclization resulted in less renal radioactivity accumulation of 111In-DOTA–ReCCMSH (8.98 ± 0.82 %ID/g) than of 111In-DOTA–CCMSH (63.2 ± 15.6 %ID/g), 111In-DOTA–CMSH (38.4 ± 3.6 %ID/g), and 111In-DOTA–NDP (12.0 ± 1.96 %ID/g) at 2 h after injection and significantly increased its clearance into the urine (92 %ID at 2 h after injection). A high radioactivity uptake ratio of tumor to normal tissue was obtained for 111In-DOTA–ReCCMSH (e.g., 489, 159, 100, and 49 for blood, muscle, lung, and liver, respectively, at 4 h after injection). Conclusion: The novel ReO-coordinated cyclic structure of DOTA-ReCCMSH contributes significantly to its enhanced tumor-targeting and renal clearance properties and makes DOTAReCCMSH an excellent candidate for melanoma radiodetection and radiotherapy.