Influence of prosthetic radioiodination on the chemical and biological behavior of chemotactic peptides labeled at high specific activity.
The influence of radioiodination made through prosthetic group N-succinimidyl-3-[131I]iodo-benzoate ([131I]SIB) on the behavior of small peptides was investigated using as model the chemotactic hexapeptide Nalpha-for-Nle-Leu-Phe-Nle-Tyr-Lys. No carrier added labeled peptide was isolated by reverse-phase HPLC (RP-HPLC) with coupling efficiencies up to 59-75%. Biodistribution in normal and infected C57 mice showed mainly a hepatobiliary clearance, a very low thyroid uptake and the highest uptake at the infection site was within 1h of injection. Superoxide production and competitive binding assays studies in human polymorphonuclear leukocytes showed a preserved biological activity and high-affinity specific binding. However, the results indicated that the changes observed in the receptor-binding properties with an IC50 almost twice than the unlabeled peptide and the increasing in the hepatobiliary excretion could be the consequence of the increased lipophicity observed due to the presence of the prosthetic group together with a strong influence of the radioisotope per se.
National Atomic Energy Commission, Ezeiza Atomic Centre, Buenos Aires, Argentina. oscar.pozzi@duke.edu
Oscar R
OR
Pozzi
Elisa O
EO
Sajaroff
Martín M
MM
Edreira
D000818:Animals; D001667:Binding, Competitive; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007463:Iodobenzoates / Q000737:chemistry*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013388:Succinimides / Q000737:chemistry* / Q000493:pharmacokinetics; D013481:Superoxides / Q000378:metabolism; D013950:Thymus Gland / Q000000981:diagnostic imaging / Q000378:metabolism; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D007463:Iodobenzoates; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D013388:Succinimides; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C021642:F-chemotactic peptide; C062337:N-succinimidyl 3-iodobenzoate