Synthesis and comparative in vivo evaluation of 99m Tc( CO ) 3 ‐labeled PEG ylated and non‐ PEG ylated cRGDfK peptide monomers

This work aimed at studying the effect of insertion of medium PEG ( PEG 7 ) on the pharmacokinetic behavior of cRGDfK peptide in comparison with the non‐ PEG ylated analogue. The cRGDfK peptide has thus been derivatized at ε‐amino group of lysine by conjugation with N 3 – PEG 7 – COOH /N 3 – CH 2 – COOH to prepare a PEG ylated and a non‐ PEG ylated analogue of cRGDfK . A tridentate chelator was then incorporated by click chemistry conjugation of the two peptide azides for radiolabeling with [ 99m Tc( CO ) 3 (H 2 O) 3 ] + precursor. Comparative in vivo evaluation of the two 99m Tc( CO ) 3 ‐labeled radiotracers, 99m Tc( CO ) 3 –Pra–Tz– CH 2 – cRGDfK 5 and 99m Tc( CO ) 3 –Pra–Tz– PEG 7 – cRGDfK 6 , was carried out in C57 BL /6 mice bearing α v β 3 ‐positive melanoma tumors to determine their potential toward targeting integrin α v β 3 receptors. 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 neutral 99m Tc( CO ) 3 radiotracers prepared exhibited receptor‐mediated uptake in melanoma tumor. The increase in the tumor uptake on introduction of PEG 7 unit was accompanied by slower clearance from other organs which resulted in decreased target‐to‐background ratios. The in vivo kinetics of 99m Tc( CO ) 3 ‐labeled radiotracer, 99m Tc( CO ) 3 –Pra–Tz– CH 2 – 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.