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Journal of medicinal chemistry

Influence of the bifunctional chelator on the pharmacokinetic properties of 99mTc(CO)3-labeled cyclic α-melanocyte stimulating hormone analog.


PMID 23414214

Abstract

Aiming at the design of specific melanocortin-1 receptor (MC1R) targeted imaging probes, we report on the effect of different azolyl-ring substitution patterns (carboxylate at the 4-position and/or methyl groups at the 3,5 positions) of pyrazolyl-diamine bifunctional chelators (Pz(2)-Pz(4)) on the pharmacokinetic profile of the (99m)Tc(CO)3-labeled lactam bridge-cyclized α-melanocyte stimulating hormone derivative, βAlaNleCycMSH(hex). Three pyrazolyl-diamine-containing chelators were conjugated to βAlaNleCycMSHhex, with the resulting peptide conjugates displaying subnanomolar MC1R binding affinity. Biodistribution studies in B16F1 melanoma-bearing mice show that all radiopeptides present a good melanoma uptake. The introduction of a carboxylate group in the azolyl-ring leads to a remarkable reduction of the kidney (>89%) and liver (>91%) accumulation for (99m)Tc(CO)3-Pz(3)-βAlaNleCycMSH(hex) and (99m)Tc(CO)3-Pz(4)-βAlaNleCycMSH(hex) when compared to the radiopeptide (99m)Tc(CO)3-Pz(1)-βAlaNleCycMSH(hex), where that group is absent. The good tumor uptake and favorable tumor-to-nontarget-organs ratios of (99m)Tc(CO)3-Pz(3)-βAlaNleCycMSH(hex) and (99m)Tc(CO)3-Pz(4)-βAlaNleCycMSH(hex) highlights the potential of both compounds as melanoma imaging agents.

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M4135
α-Melanocyte stimulating hormone, ≥97% (HPLC)
C77H109N21O19S