title: Synthesis and comparative in vivo evaluation of99mTc(CO)3-labeled PEGylated and non-PEGylated cRGDfK peptide monomers.
abstract: This work aimed at studying the effect of insertion of medium PEG (PEG7) on the pharmacokinetic behavior of cRGDfK peptide in comparison with the non-PEGylated analogue. The cRGDfK peptide has thus been derivatized at ε-amino group of lysine by conjugation with N3-PEG7-COOH/N3-CH2-COOH to prepare a PEGylated and a non-PEGylated analogue of cRGDfK. A tridentate chelator was then incorporated by click chemistry conjugation of the two peptide azides for radiolabeling with [99mTc(CO)3(H2O)3]+precursor. Comparative in vivo evaluation of the two99mTc(CO)3-labeled radiotracers,99mTc(CO)3-Pra-Tz-CH2-cRGDfK 5 and99mTc(CO)3-Pra-Tz-PEG7-cRGDfK 6, was carried out in C57BL/6 mice bearing αvβ3-positive melanoma tumors to determine their potential toward targeting integrin αvβ3receptors. The radiotracers exhibited excellent stability in saline as well as in serum. Maximum tumor uptake for the two radiotracers was observed at 30 min p.i. (5: 3.0 ± 0.7% ID/g; 6: 4.1 ± 0.5% ID/g). The two neutral99mTc(CO)3radiotracers prepared exhibited receptor-mediated uptake in melanoma tumor. The increase in the tumor uptake on introduction of PEG7unit was accompanied by slower clearance from other organs which resulted in decreased target-to-background ratios. The in vivo kinetics of99mTc(CO)3-labeled radiotracer,99mTc(CO)3-Pra-Tz-CH2-cRGDfK 5 with only methylene unit as the spacer, was found to be more favorable due to higher tumor/blood, tumor/liver, tumor/kidney, and tumor/lung ratios.
authors: Radiopharmaceuticals Chemistry Section, Radiochemistry & Isotope Group, Bhabha Atomic Research Centre, Mumbai, India.
authors: Kusum
authors: K
authors: Vats
authors: Radiopharmaceuticals Chemistry Section, Radiochemistry & Isotope Group, Bhabha Atomic Research Centre, Mumbai, India.
authors: Drishty
authors: D
authors: Satpati
authors: Radiopharmaceuticals Chemistry Section, Radiochemistry & Isotope Group, Bhabha Atomic Research Centre, Mumbai, India.
authors: Rohit
authors: R
authors: Sharma
authors: Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai, India.
authors: Haladhar D
authors: HD
authors: Sarma
authors: Radiopharmaceuticals Chemistry Section, Radiochemistry & Isotope Group, Bhabha Atomic Research Centre, Mumbai, India.
authors: Sharmila
authors: S
authors: Banerjee
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D057930:Click Chemistry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy; D008810:Mice, Inbred C57BL; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012211:Rhenium / Q000737:chemistry; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D039302:Integrin alphaVbeta3; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C099250:cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl); D011092:Polyethylene Glycols; D012211:Rhenium; D013667:Technetium; D008239:Lysine
keywords: 
  cRGDfK
  ; C57BL/6; [99mTc(CO)3(H2O)3]+; click chemistry; melanoma; polyethylene glycol (PEG)