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- Title
Synthesis and comparative in vivo evaluation of <sup>99m</sup>Tc( CO)<sub>3</sub>-labeled PEGylated and non- PEGylated cRGDfK peptide monomers.
- Authors
Vats, Kusum; Satpati, Drishty; Sharma, Rohit; Sarma, Haladhar D.; Banerjee, Sharmila
- 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 two 99mTc( CO)3-labeled radiotracers, 99mTc( CO)3-Pra-Tz- CH2- cRGDfK 5 and 99mTc( CO)3-Pra-Tz- PEG7- cRGDfK 6, was carried out in C57 BL/6 mice bearing αvβ3-positive melanoma tumors to determine their potential toward targeting integrin αvβ3 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 99mTc( CO)3 radiotracers prepared exhibited receptor-mediated uptake in melanoma tumor. The increase in the tumor uptake on introduction of PEG7 unit was accompanied by slower clearance from other organs which resulted in decreased target-to-background ratios. The in vivo kinetics of 99mTc( 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.
- Subjects
PHARMACOKINETICS; PEPTIDES; AZIDES; MELANOMA; RADIOACTIVE tracers
- Publication
Chemical Biology & Drug Design, 2017, Vol 89, Issue 3, p371
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.12844