Melanocortin‐1 receptor‐targeting with radiolabeled cyclic α‐melanocyte‐stimulating hormone analogs for melanoma imaging

Abstract

Melanoma is a type of skin cancer known for its high aggressiveness, early dissemination of metastases, and poor prognosis once metastasized. Thus, early diagnosis of melanoma is a key issue for increasing patient survival. The overexpression of melanocortin-1 receptors (MC1R) in isolated melanoma cells and melanoma tissues led to the radiolabeling of several linear and cyclic MC analogs for melanoma imaging or therapy. Cyclization of α-melanocyte stimulating hormone (α-MSH) peptides has been successfully used to improve binding affinity and in vivo stability of peptides. Herein, we describe the different peptide cyclization strategies recently reported for radiolabeled α-MSH analogs and discuss how such strategies affect MC1R binding affinity, pharmacokinetic profile, and MC1R-melanoma imaging. This review also highlights how the nature of the radiometal and labeling approach influence those properties. Among the cyclized α-MSH peptides reported, (99m)Tc/(111)In-labeled metal-cyclized and lactam bridge-cyclized peptides displayed the highest melanoma and lowest renal uptake values in B16/F1 melanoma-bearing mice and became the most promising tools to be further explored as potential melanoma imaging probes.

Evaluation of novel 99mTc(I)-labeled homobivalent α-melanocyte-stimulating hormone analogs for melanocortin-1 receptor targeting

“…After neutralization with HCl 1 M at 0°C and evaporation of solvent, the obtained crude product was purified by solid phase extraction using Sep-Pack C 18 Synthesis of fac-[Re(CO) 3 (k 3 -pz(CO 2 H))] ?…”

“…The replacement of Met 4 and Phe 7 by Nle 4 and D-Phe 7 led to the potent a-MSH analog (Nle 4 , D-Phe 7 )-a-MSH (NDP-MSH) with subnanomolar receptor affinity and resistance to enzymatic degradation [19][20][21]. Among the linear a-MSH analogs explored for melanoma imaging, [Ac-Nle 4 , Asp 5 , or single photon emission computed tomography ( 111 In, 67 Ga, 99m Tc) imaging [11,12,14,18,22].…”

“…Therefore, the design of novel radioactive compounds for melanoma imaging or therapy became a quite attractive approach for the management of both metastatic and nonmetastatic melanoma patients [1,8]. The melanocortin type 1 receptor (MC1R) is overexpressed in both melanotic and amelanotic murine and human melanoma cells, and has been explored as a specific molecular target for melanoma detection [8][9][10][11][12][13][14][15][16][17][18]. a-Melanocyte-stimulating hormone (a-MSH), a linear tridecapeptide (Ac-Ser 1 -Tyr 2 -Ser 3 -Met 4 -Glu 5 -His 6 -Phe 7 -Arg 8 -Trp 9 -Gly 10 -Lys 11 -Pro 12 -Val 13 -NH 2 ), is the native ligand that binds to the five subtypes of melanocortin receptors (MC1R-MC5R) [19][20][21].…”

“…After neutralization of the reaction solution with1 M HCl at 0°C and evaporation of the solvent, the crude product obtained was purified with use of a Sep-Pack C18 cartridge (H 2 O/MeOH 0-100%), giving 12-(2-carboxyethyl)-8-(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)-2,2-dimethyl-4-oxo-3-oxa-5,8,12-triazapentadecan-15-oic acid [pz(Boc)(CO 2 H) 2 -A] as a white solid. Yield: 75% (0.05 g; 0.1 mmol…”

An electrochemical immunosensing method for detecting melanoma cells

“…It is expressed in a majority (>80%) of melanoma lines and also primary and meta-static cutaneous melanomas compared to other cell surface markers (Raposinho et al, 2010; Salazar-Onfray et al, 2002; Schwahn et al, 2001; Xia et al, 1996). It is also useful marker for the diagnosis of uveal melanoma.…”