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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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References

  1. 1.

    Policard A (1924) Etudes sur les aspects offerts par des tumeurs experimentales examinees a la lumiere de woods. C R Soc Biol 91:14–32

  2. 2.

    Josefsen LB, Boyle RW (2012) Unique diagnostic and therapeutic roles of porphyrins and phthalocyanines in photodynamic therapy, imaging and theranostics. Theranostics 2:916–966

  3. 3.

    Kaye AH, Morstyn G, Apuzzo MJ (1988) Photoradiation therapy and its potential in the management of neurological tumors. J Neurosurg 69:1–14

  4. 4.

    Sarma HD, Das T, Banerjee S et al (2010) Biologic evaluation of a novel 188Re-labeled porphyrin in mice tumor model. Cancer Biother Radiopharm 25:47–54

  5. 5.

    Banerjee S, Das T, Samuel G et al (2001) A novel [186/188Re]-labelled porphyrin for targeted radiotherapy. Nucl Med Commun 22:1101–1107

  6. 6.

    Das T, Chakraborty S, Sarma HD et al (2010) A novel 177Lu-labeled porphyrin for possible use in targeted tumor therapy. Nucl Med Biol 37:655–663

  7. 7.

    Mittal S, Bhadwal M, Das T et al (2013) Synthesis and biological evaluation of 90Y-labeled DOTA-porphyrin conjugate: a potential molecule for targeted tumor therapy. Cancer Biother Radiopharm 28:651–656

  8. 8.

    Maziere JC, Santus R, Morliere P et al (1990) Cellular uptake and photosensitizing properties of anticancer porphyrins in cell membranes and low- and high-density lipoproteins. J Photochem Photobiol B 6:61–68

  9. 9.

    Lazzeri D, Durantini EN (2003) Synthesis of meso-substituted cationic porphyrins as potential photodynamic agents. ARKIVOC 10:227–239

  10. 10.

    Driaf K, Granet R, Krausz P et al (1996) Synthesis of glycosylated cationic porphyrins as potential agents in photodynamic therapy. Can J Chem 74:1550–1563

  11. 11.

    Biron E, Voyer N (2005) Synthesis of cationic porphyrin modified amino acids. Chem Commun 37:4652–4654

  12. 12.

    Brˇiza T, Kralova J, Kigler P (2012) Combination of two chromophores: synthesis and PDT application of porphyrin-pentamethinium conjugate. Bioorg Med Chem Lett 22:82–84

  13. 13.

    Schwach G, Thamyongkit P, Reith LM et al (2012) A water soluble tri-cationic porphyrin-EDTA conjugate induces apoptosis in human neuroendocrine tumor cell lines. Bioorg Chem 40:108–113

  14. 14.

    Aviezer D, Cotton S, David M et al (2000) Porphyrin analogues as novel antagonists of fibroblast growth factor and vascular endothelial growth factor receptor binding that inhibit endothelial cell proliferation, tumor progression, and metastasis. Cancer Res 60:2973–2980

  15. 15.

    Gantchev TG, Ali H, van Lier JE (1993) Interactions of chloroaluminium-tetramethyl-tetrapyridino-porphyrazine with DNA. Eur J Biochem 217:371–376

  16. 16.

    Izbicka E, Wheelhouse RT, Raymond E et al (1999) Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells. Cancer Res 59:639–644

  17. 17.

    Sehlstedt U, Kim SK, Carter P et al (1994) Interaction of cationic porphyrins with DNA. Biochemistry 33:417–426

  18. 18.

    Sari MA, Battioni JP, Dupre D et al (1990) Interaction of cationic porphyrins with DNA: importance of the number and position of the charges and minimum structural requirements for intercalation. Biochemistry 29:4205–4215

  19. 19.

    Zoller F, Riss PJ, Montforts FP et al (2013) Radiolabelling and preliminary evaluation of 68Ga-tetrapyrrole derivatives as potential tracers for PET. Nucl Med Biol 40:280–288

  20. 20.

    Velikyan I (2014) Prospective of 68Ga-radiopharmaceutical development. Theranostics 4:47–80

  21. 21.

    Shetty D, Lee YS, Jeong JM (2010) 68Ga-Labeled radiopharmaceuticals for positron emission tomography. Nucl Med Mol Imaging 44:233–240

  22. 22.

    Fazaeli Y, Jalilian AR, Amini MM et al (2012) Development of a 68Ga-fluorinated porphyrin complex as a possible PET imaging agent. Nucl Med Mol Imaging 46:20–26

  23. 23.

    Paknafas A, Fazaeli Y, Jalilian AR et al (2013) Radiosynthesis and quality control of [67Ga]-3,4-dimethoxylated porphyrin complex as a possible imaging agent. Iran J Pharm Res 12:735–744

  24. 24.

    Das T, Chakraborty S, Sarma HD et al (2012) 109Pd-5,10,15,20-tetrakis[4-carboxymethyleneoxyphenyl]porphyrin: a potential agent for targeted tumor therapy. Curr Radiopharm 5:340–347

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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.

Author information

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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Key words

  • 68Ga
  • Cationic porphyrin
  • Radiolabeled porphyrin
  • PET imaging of tumor