title: Influence of the bifunctional chelator on the pharmacokinetic properties of 99mTc(CO)3-labeled cyclic α-melanocyte stimulating hormone analog.
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.
authors: Unidade de Ciências Químicas e Radiofarmacêuticas, IST/ITN, Instituto Superior Técnico, Universidade Técnica de Lisboa, Estrada Nacional 10, 2686-953, Sacavém, Portugal.
authors: Maurício
authors: M
authors: Morais
authors: Bruno L
authors: BL
authors: Oliveira
authors: João D G
authors: JD
authors: Correia
authors: Maria Cristina
authors: MC
authors: Oliveira
authors: Maria Angeles
authors: MA
authors: Jiménez
authors: Isabel
authors: I
authors: Santos
authors: Paula D
authors: PD
authors: Raposinho
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry*; D004355:Drug Stability; D006801:Humans; D008546:Melanoma, Experimental / Q000175:diagnosis / Q000378:metabolism; D051379:Mice; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D044102:Receptor, Melanocortin, Type 1 / Q000737:chemistry / Q000378:metabolism; D013667:Technetium / Q000493:pharmacokinetics; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D002614:Chelating Agents; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D044102:Receptor, Melanocortin, Type 1; D000521:alpha-MSH; D013667:Technetium