1. 68Ga-1,4,7,10-Tetraazacyclododecane- N, N', N'', N'''-1,4,7,10-tetraacetic acid-rhenium-cyclized-[Cys3,4,10,D-Phe7,Arg11]α-MSH3-13
Kam Leung
Malignant melanoma is the most deadly form of skin cancer (1). Early and accurate diagnosis is necessary for surgery and successful treatment (2). The melanocortin (MC) system is a neuropeptide network of the skin, and it is involved in pigmentation regulation, cortisol production, and many other physiological processes (3). Most cutaneous cell types express MC receptors, pro-opiomelanocortin (POMC), and prohormone convertases, and they also release MCs. Melanotropin-stimulating hormones (α-, β-, and γ-MSH) are derived from POMC by the proteolytic action of prohormone convertases. There are five MC receptors (MC1R to MC5R), which belong to the G-protein-coupled receptor superfamily. However, these receptors have been found to be overexpressed in melanoma cells (4, 5). α-MSH (Ac-Ser1-Tyr2-Ser3-Met4-Glu5-His6-Phe7-Arg8-Trp9-Gly10-Lys11-Pro12-Val13-NH2), produced by the brain and pituitary gland, is a tridecapeptide (13 amino acids) and is the most potent melanotropic peptide (6) in the regulation of skin pigmentationviathe MC1R.Although positron emission tomography (PET) imaging with [18F]fluoro-2-deoxy-2-d-glucose ([18F]FDG) is effective in the detection of melanoma, it is not melanoma-specific and some melanoma cells do not take up [18F]FDG (7, 8). Radiolabeled α-MSH peptide analogs have been shown to specifically bind to MC1R that is overexpressed on human and mouse melanoma cells (4, 5, 7, 9, 10). 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) has been successfully coupled to the α-MSH peptide analogs for radiolabeling with a variety of radionuclides (7). To improve the tumor/kidney uptake ratio and metabolic stability, a rhenium-cyclized α-MSH analog, Re-[Cys3,4,10,D-Phe7,Arg11]α-MSH3-13(Re-CCMSH(Arg11)), was conjugated with DOTA. DOTA-Re-CCMSH(Arg11) was radiolabeled with68Ga as a potential molecular imaging agent to target melanoma.68Ga is a positron emitter with a physical half-life of 68 min and is suitable for PET imaging.
2. 68Ga-CHX-A"-Rhenium-cyclized-[Cys3,4,10,D-Phe7,Arg11]α-MSH3-13
Kam Leung
Malignant melanoma is the most deadly form of skin cancer (1). Early and accurate diagnosis is necessary for surgery and successful treatment (2). The melanocortin (MC) system is a neuropeptide network of the skin, and it is involved in pigmentation regulation, cortisol production, and many other physiological processes (3). Most cutaneous cell types express MC receptors, pro-opiomelanocortin (POMC), and prohormone convertases, and they also release MCs. Melanotropin-stimulating hormones (α-, β-, and γ-MSH) are derived from POMC by the proteolytic action of prohormone convertases. There are five MC receptors (MC1R to MC5R), which belong to the G-protein-coupled receptor superfamily, and these receptors have been found to be overexpressed in melanoma cells (4, 5). α-MSH (Ac-Ser1-Tyr2-Ser3-Met4-Glu5-His6-Phe7-Arg8-Trp9-Gly10-Lys11-Pro12-Val13-NH2), produced by the brain and the pituitary gland, is a tridecapeptide (13 amino acids) and is the most potent melanotropic peptide (6) in the regulation of skin pigmentationviaMC1R.Positron emission tomography (PET) imaging with [18F]fluoro-2-deoxy-2-d-glucose ([18F]FDG) in cancer has been approved by United States Food and Drug Administration with many on-going clinical trials. Although [18F]FDG is effective in the detection of melanoma, it is not melanoma-specific and some melanoma cells do not take up [18F]FDG (7, 8). Radiolabeled α-MSH peptide analogs have been shown to specifically bind to MC1R that is overexpressed on human and mouse melanoma cells (4, 5, 7, 9, 10).N-(2-Aminoethyl)-trans-1,2-diaminocyclohexane-N,N",N"'-pentaacetic acid (CHX-A") has been successfully coupled to α-MSH peptide analogs for radiolabeling with a variety of radionuclides (7, 11, 12). A rhenium-cyclized α-MSH analog, Re-[Cys3,4,10,D-Phe7,Arg11]α-MSH3-13(ReCCMSH(Arg11)), was conjugated with CHX-A" (CHX-A"-ReCCMSH(Arg11)) and radiolabeled with68Ga (68Ga-CHX-A"-ReCCMSH(Arg11)) as a potential molecular imaging agent to target melanoma (13).Rhenium-mediated cyclization exhibits significantly reduced nonspecific renal radioactivity accumulation high tumor uptake and retention coupled with rapid clearance kinetics, compared with its free sulfhydryl and disulfide bond-containing counterparts (10).68Ga is a positron emitter with a physical half-life of 68 min and is suitable for PET imaging.
3. 86Y-DOTA-rhenium-cyclized-[Cys3,4,10,D-Phe7,Arg11]α-MSH3-13
Kam Leung
Malignant melanoma is the most deadly form of skin cancer (1). Early and accurate diagnosis is necessary for surgery and successful treatment (2). The melanocortin (MC) system is a neuropeptide network of the skin, and it is involved in pigmentation regulation, cortisol production, and many other physiological processes (3). Most cutaneous cell types express MC receptors, pro-opiomelanocortin (POMC), and prohormone convertases, and they also release MCs. Melanotropin-stimulating hormones (α-, β-, and γ-MSH) are derived from POMC by the proteolytic action of prohormone convertases. There are five MC receptors (MC1R to MC5R), which belong to the G-protein-coupled receptor superfamily. However, these receptors have been found to be overexpressed in melanoma cells (4, 5). α-MSH (Ac-Ser1-Tyr2-Ser3-Met4-Glu5-His6-Phe7-Arg8-Trp9-Gly10-Lys11-Pro12-Val13-NH2), produced by the brain and pituitary gland, is a tridecapeptide (13 amino acids) and is the most potent melanotropic peptide (6) in the regulation of skin pigmentation via the MC1R.Although positron emission tomography (PET) imaging with [18F]fluoro-2-deoxy-2-d-glucose ([18F]FDG) is effective in the detection of melanoma, it is not melanoma-specific and some melanoma cells do not take up [18F]FDG (7, 8). Radiolabeled α-MSH peptide analogs have been shown to specifically bind to MC1R that is overexpressed on human and mouse melanoma cells (4, 5, 7, 9, 10). 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) has been successfully coupled to the α-MSH peptide analogs for radiolabeling with a variety of radionuclides (7).111In-,64Cu- and 99mTc-DOTA-Re(Arg11)CCMSH showed favorable tumor imaging properties in mice bearing murine melanoma (11). A rhenium-cyclized α-MSH analog, Re-[Cys3,4,10,D-Phe7,Arg11]α-MSH3-13(Re-CCMSH(Arg11)), was conjugated with DOTA. DOTA-Re-CCMSH(Arg11) was radiolabeled with86Y as a potential molecular imaging agent to target melanoma (12).86Y is a positron emitter with a physicalt½of 14.7 h and is suitable for PET imaging.
