A Systematic Comparative Evaluation of â¶â¸Ga-Labeled RGD Peptides Conjugated with Different Chelators
10.1007/s13139-017-0499-0
- Author:
Akanksha JAIN
1
;
Sudipta CHAKRABORTY
;
H D SARMA
;
Ashutosh DASH
Author Information
1. Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, India. sudipta@barc.gov.in, adash@barc.gov.in
- Publication Type:Original Article
- From:Nuclear Medicine and Molecular Imaging
2018;52(2):125-134
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE:The present paper reports a systematic study on the effect of bifunctional chelators (BFC) namely, NOTA, DOTA, and DTPA, on the radiochemical formulation, in vitro stability, and in vivo biological properties of â¶â¸Ga-labeled RGD peptide derivatives.
METHODS:The three RGD conjugates namely, NOTA-Bn-E-[c(RGDfk)]â‚‚, DOTA-Bn-E-[c(RGDfk)]â‚‚, and DTPA-Bn-E-[c(RGDfk)]â‚‚ were radiolabeled with â¶â¸Ga and the radiolabeling was optimized with respect to the ligand amount, radiolabeling time, and temperature. Further, the â¶â¸Ga complexes were assessed for their in vitro and in vivo stabilities. The biodistribution studies of the three radiolabeled conjugates were carried out in C57BL/6 mice bearing melanoma tumor at 30 min and 1 h post-adimistration.
RESULTS:NOTA-Bn-E-[c(RGDfk)]â‚‚ could be radiolabeled with â¶â¸Ga at room temperature while DOTA-Bn-E-[c(RGDfk)]â‚‚ and DTPA-Bn-E-[c(RGDfk)]â‚‚ were radiolabeled at high temperature. â¶â¸Ga-NOTA-Bn-E-[c(RGDfk)]â‚‚ was found to be the most kinetically rigid in in vitro stability assay. The uptake of the three radiolabeled peptide conjugates in melanoma tumor was comparable at 1 h post-administration (NOTA; DOTA; DTPA (% I.D./g):: 2.78 ± 0.38; 3.08 ± 1.1; 3.36 ± 0.49). However, the tumor/background ratio of â¶â¸Ga-NOTA-Bn-E-[c(RGDfk)]â‚‚ was the best amongst the three radiotracers. â¶â¸Ga-complexes of NOTA-Bn-E-[c(RGDfk)]â‚‚ and DOTABn-E-[c(RGDfk)]â‚‚ showed excellent in vivo stability while â¶â¸Ga-DTPA-Bn-E-[c(RGDfk)]â‚‚ showed significant metabolic degradation.
CONCLUSION:These studies show that â¶â¸Ga-NOTA-Bn-E-[c(RGDfk)]â‚‚ would be the most appropriate â¶â¸Ga-labeled radiotracer and the most amenable for kit formulation.
