Nucl Med Mol Imaging.  2018 Apr;52(2):125-134. 10.1007/s13139-017-0499-0.

A Systematic Comparative Evaluation of ⁶⁸Ga-Labeled RGD Peptides Conjugated with Different Chelators

• Jain A
• Chakraborty S
• Sarma HD
• Dash A

• KMID: 2414800
• DOI: http://doi.org/10.1007/s13139-017-0499-0

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 ⁶⁸Ga-labeled RGD peptide derivatives.
METHODS
The three RGD conjugates namely, NOTA-Bn-E-[c(RGDfk)]₂, DOTA-Bn-E-[c(RGDfk)]₂, and DTPA-Bn-E-[c(RGDfk)]₂ were radiolabeled with ⁶⁸Ga and the radiolabeling was optimized with respect to the ligand amount, radiolabeling time, and temperature. Further, the ⁶⁸Ga 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 ⁶⁸Ga at room temperature while DOTA-Bn-E-[c(RGDfk)]â‚‚ and DTPA-Bn-E-[c(RGDfk)]â‚‚ were radiolabeled at high temperature. ⁶⁸Ga-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 ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]â‚‚ was the best amongst the three radiotracers. ⁶⁸Ga-complexes of NOTA-Bn-E-[c(RGDfk)]â‚‚ and DOTABn-E-[c(RGDfk)]â‚‚ showed excellent in vivo stability while ⁶⁸Ga-DTPA-Bn-E-[c(RGDfk)]â‚‚ showed significant metabolic degradation.
CONCLUSION
These studies show that ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ would be the most appropriate ⁶⁸Ga-labeled radiotracer and the most amenable for kit formulation.

Keyword

Tumor angiogenesis; PETimaging; RGD peptides; ⁶⁸Ga; Bifunctional chelators

MeSH Terms

Animals
Chelating Agents*
In Vitro Techniques
Melanoma
Mice
Pentetic Acid
Peptides*
Chelating Agents
Pentetic Acid
Peptides