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

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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)]2 could be radiolabeled with 68Ga at room temperature while DOTA-Bn-E-[c(RGDfk)]2 and DTPA-Bn-E-[c(RGDfk)]2 were radiolabeled at high temperature. 68Ga-NOTA-Bn-E-[c(RGDfk)]2 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)]2 was the best amongst the three radiotracers. 68Ga-complexes of NOTA-Bn-E-[c(RGDfk)]2 and DOTA-Bn-E-[c(RGDfk)]2 showed excellent in vivo stability while 68Ga-DTPA-Bn-E-[c(RGDfk)]2 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.

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Acknowledgments

The authors are thankful to Dr. Aruna Korde, Head, Radiopharmaceutical Evaluation Section, Radiopharmaceuticals Division, BARC for providing access to the 68Ge/68Ga generator. Thanks are also due to Dr. B.S. Tomar, Director, Radiochemistry & Isotope Group, BARC for his support and encouragement.

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Authors and Affiliations

  1. Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India

    Akanksha Jain, Sudipta Chakraborty & Ashutosh Dash

  2. Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400 094, India

    Akanksha Jain, Sudipta Chakraborty & Ashutosh Dash

  3. Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre,Trombay, Mumbai, 400 085, India

    H. D. Sarma

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  1. Akanksha Jain
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  2. Sudipta Chakraborty
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Correspondence to Sudipta Chakraborty or Ashutosh Dash.

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Conflict of Interest

Akanksha Jain, Sudipta Chakraborty, Haladhar Dev Sarma and Ashutosh Dash, declare that they have no conflict of interest financial, scientific or otherwise in the publication of this article. Research at the Bhabha Atomic Research Centre (BARC) is part of the ongoing activities of the Department of Atomic Energy, India and is fully supported by government funding.

Ethical Approval

All procedures performed in studies involving animals were in strict compliance with the approved protocols of Institutional Animal Ethics Committee of BARC, India.

Informed Consent

The institutional review board of our institute, BARC, approved this retrospective study, and the requirement to obtain informed consent was waived.

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Jain, A., Chakraborty, S., Sarma, H.D. et al. A Systematic Comparative Evaluation of 68Ga-Labeled RGD Peptides Conjugated with Different Chelators. Nucl Med Mol Imaging 52, 125–134 (2018). https://doi.org/10.1007/s13139-017-0499-0

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  • DOI: https://doi.org/10.1007/s13139-017-0499-0

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