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Radiosynthesis and Bioevaluation of [68Ga]-Labeled 5,10,15,20-Tetra(4-methylpyridyl)-porphyrin for Possible Application as a PET Radiotracer for Tumor Imaging

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Abstract

Purpose

Porphyrins have inherent ability to localize preferentially in tumor lesions. Cationic porphyrins are readily water soluble and reported to exhibit strong DNA-binding capabilities. Therefore, attempt has been made to prepare a water soluble [68Ga]-labeled cationic porphyrin, viz., 5,10,15,20-tetra(4-methylpyridyl)porphyrin (TMP), and evaluate its potential as a positron emission tomography (PET) radiotracer for tumor imaging.

Procedures

The cationic porphyrin TMP was synthesized following a two-step procedure and subsequently radiolabeled with Ga-68, eluted from a commercial 68Ge/68Ga generator. Purification of the [68Ga]-labeled porphyrin derivative was carried out using Sep-Pak® cartridges. The tumor-targeting potential of the [68Ga]-labeled-5,10,15,20-tetra(4-methylpyridyl)porphyrin was evaluated by biodistribution studies in Swiss mice bearing fibrosarcoma tumor.

Results

Under optimized reaction conditions, [68Ga]-labeled TMP was obtained with ~90 % radiochemical purity which was subsequently improved to >99 % after purification through Sep-Pak® cartridges. Biodistribution studies revealed high tumor uptake of the radiotracer within 30-min post-injection (6.47 ± 0.87 % of injected activity) and retention until the final 2 h post-administration (4.48 ± 1.11 % of injected activity) time point. The initial uptake observed in non-target organs cleared away with time resulting in gradually improving tumor/blood and tumor/muscle ratios.

Conclusion

Preliminary bioevaluation studies indicated the potential of the radiolabeled porphyrin derivative for tumor imaging, and further detailed studies are warranted to evaluate the true potential of the developed radiotracer.

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Acknowledgments

The authors are thankful to Dr. Gursharan Singh, Head, Isotope Applications and Radiopharmaceuticals Division and Associate Director (I), Radiochemistry and Isotope Group, Bhabha Atomic Research Centre (BARC) for his support. The authors are grateful to Dr. M.G.R. Rajan, Head, Radiation Medicine Centre, BARC for kindly providing the 68Ge/68Ga generator, which was used for the present study.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Isotope Applications and Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, 400085, India

    Mohini Bhadwal, Tapas Das & Sharmila Banerjee

  2. Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India

    Haladhar Dev Sarma

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  1. Mohini Bhadwal
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  2. Tapas Das
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  4. Sharmila Banerjee
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Correspondence to Sharmila Banerjee.

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Bhadwal, M., Das, T., Dev Sarma, H. et al. Radiosynthesis and Bioevaluation of [68Ga]-Labeled 5,10,15,20-Tetra(4-methylpyridyl)-porphyrin for Possible Application as a PET Radiotracer for Tumor Imaging. Mol Imaging Biol 17, 111–118 (2015). https://doi.org/10.1007/s11307-014-0760-1

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  • DOI: https://doi.org/10.1007/s11307-014-0760-1

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