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Rhenium-188 labelled meso-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl] porphyrin for targeted radiotherapy: preliminary biological evaluation in mice

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

This study focusses on a promising carrier system for therapeutic and imaging purposes using meso-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl] porphyrin (T3,4CPP). To assess its potential for clinical use, we labelled T3,4CPP with 188Re and analysed some kinetic biodistribution parameters after intravenous injection in mice.

Materials and methods

T3,4CPP was synthesized and labelled with 188Re. Normal Kunming (KM) mice and melanoma- or hepatoma-bearing BALB/c nude mice were injected intravenously with 5.55 MBq 188Re-labelled T3,4CPP and sacrificed at 0.5, 2, 4, and 24 h and 8, and 24 h, respectively.

Results

The 188Re-T3,4CPP yield was more than 95% with specific activity 16.9 GBq (mol)−1, and Vitamin C (VC) could increase its stability in vitro. In normal KM mice, 188Re-T3,4CPP had fast blood clearance (~99%, 24 h postinjection), low retention in the vital organs and hepatotropic characteristics. In nude mice, more than 4.4 and 6.1% uptake per gram of tumour (%ID g−1) at 8 h postinjection was in melanoma and hepatoma, respectively; this remained as high levels after 24 h as 4.6 and 6.5%, respectively. At 8 h, the tumour/blood and tumour/muscle (T/M) ratios in melanomas and hepatoma bearing mice were 7.3, 13,and 7.0, 20, respectively. Twenty-four hours later, these high ratios still continued in existence which were 9.6, 19 and 10, 25, respectively.

Conclusion

The results obtained in this study indicate that 188Re-T3,4CPP has better tumour affinity and retainable accumulation characteristics in carcinoma which can potentially be used for tumour-targeted radiotherapy.

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References

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

    Google Scholar 

  2. Figge FHJ, Weiland GS, Manganiello LOJ. Cancer detection and therapy: affinity of neoplastic, embryonic and traumatized tissues for porphyrin and metalloporphyrin. Proc Soc Exp Biol Med. 1948;68:640-1.

    Article  CAS  PubMed  Google Scholar 

  3. Manganiello LOJ, Figge FHJ. Cancer detection and therapy II: methods of preparation and biological effects of metalloporphyrin. Bull School Med Univ Maryland. 1951;36:3-7.

    CAS  Google Scholar 

  4. Peck GC, Mack HP, Figge FHJ. Cancer detection and therapy III: affinity of lymphatic tissues for hematoporphyrin. Bull School Med Univ Maryland. 1953;38:124-7.

    CAS  Google Scholar 

  5. Winkelman J. Intracellular localization of hematoporphyrin in a transplanted tumour. J Natl Cancer Inst. 1961;27:1369-77.

    CAS  PubMed  Google Scholar 

  6. Lipson RL, Baldes EJ, Gray MS. Hematoporphyrin derivative for detection and management of cancer. Cancer. 1967;20:2255-7.

    Article  CAS  PubMed  Google Scholar 

  7. Fawwaz RA, Wang TST, Alderson PO. Evaluation of radioporphyrins as tumour seeking agents in experimental animals. J Nucl Med. 1981;22:P50.

    Google Scholar 

  8. Jori G. Tumour photosensitizers: approaches to enhance selectivity and efficiency of photodynamic therapy. J Photochem Photobiol B: Biol. 1996;36:87-93.

    Article  CAS  Google Scholar 

  9. Wong DW. A simple method of labeling hematoporphyrin derivative with technetium-99m. J Label Comp Radiopharm. 1983;20:351-61.

    Article  CAS  Google Scholar 

  10. Shetty SJ, Murugesan S, Chatterjee S, et al. A new 99mTc labelled porphyrin for specific imaging of sarcoma 120: synthesis and biological study in a Swiss mouse model. J Label Comp Radiopharm. 1996;38:411-8.

    Article  CAS  Google Scholar 

  11. Chatterjee SR, Murugesan S, Kamat JP, et al. Photodynamic effects induced by meso-tetrakis[4-(carboxymethyleneoxy)phenyl] porphyrin using rat hepatic microsomes as model membranes. Arch Biochem Biophys. 1997;339:242-9.

    Article  CAS  PubMed  Google Scholar 

  12. Murugesan S, Shetty SJ, Srivastava TS, et al. Evaluation studies of technetium-99m-porphyrin (T3,4BCPP) for tumor imaging. J Porphyrins Phthalocyanines. 2001;5:824-8.

    Article  Google Scholar 

  13. Murugesan S, Shetty SJ, Srivastava TS, et al. Preparation and biological evaluation of the new chlorin photosensitizer T3,4BCPC for detection and treatment of tumors. J Photoch Photobio B. 2002;68:33-8.

    Article  CAS  Google Scholar 

  14. Crudo JL, Edreira MM, Obenaus ER, et al. Labelling of the anti-melanoma 14f7 monoclonal antibody with rhenium-188-MAG3 chelate: conjugation optimization, in vitro stability and animal studies. J Radioanal Nucl Chem. 2004;261:337-42.

    Article  CAS  Google Scholar 

  15. Antoccia A, Banzato A, Bello M, et al. 188Rhenium-induced cell death and apoptosis in a panel of tumor cell lines. Nucl Instrum Meth A. 2007;571(1/2):471-4.

    Article  CAS  Google Scholar 

  16. Knapp Jr FF, Callahan AP, Beets AL, et al. Processing of reactor produced 188W for fabrication of clinical scale alumina based 188W/188Re generator. Appl Radiat Isot. 1994;45:1123-8.

    Article  Google Scholar 

  17. Pillai MRA, Samuel G, Banerjee S, et al. Technetium-99 m complexes of polydentate amine-pyrrole and amine-thiophene ligands. Nucl Med Biol. 1999;26:69-77.

    Article  CAS  PubMed  Google Scholar 

  18. Ning YC. Mass spectrogram analysis: the mass chromatogram of benzene compound. Structural identification of organic compounds and organic spectroscopy. 2ndnd ed. Beijing: Science; 2000. p. 301-03.

    Google Scholar 

  19. Luo SZ, Pu MF, QJ, et al. Formation of a potential tumor therapeutic pharmaceutical 186Re-bleomycin. Nucl Sci Tech. 1998;9(1):26-8.

  20. Jeong JM, Chung JK. Therapy with 188Re-labelled radiopharmaceuticals: an overview of promising results from initial clinical trials. Cancer Biother Radio. 2003;18:707-17.

    Article  CAS  Google Scholar 

  21. Shetty SJ, Murugesan S, Srivastava TS, Noronha OPD, Samuel AM. Indian Patent AA No. 2761 1999.

  22. Nakajima S, Takemura T, Sakata I, et al. Tumor-localizing activity of porphyrin and its affinity to LDL, transferring. Cancer Lett. 1995;92(1):113-8.

    Article  CAS  PubMed  Google Scholar 

  23. Shibata Y, Matsumura A, Yoshida F, et al. Competitive uptake of porphyrin and LDL via the LDL receptor in glioma cell lines: flow cytometric analysis. Cancer Lett. 2001;166(1):79-87.

    Article  CAS  PubMed  Google Scholar 

  24. Nakajima S, Moriyama T, Hayashi H, et al. Hemopexin as a carrier protein of tumor-localizing Ga-metalloporphyrin-ATN-2. Cancer Lett. 2000;149(1-2):221-6.

    Article  CAS  PubMed  Google Scholar 

  25. Shibata Y, Matsumura A, Yoshida F, et al. Cell cycle dependency of porphyrin uptake in a glioma cell line. Cancer Lett. 1998;129(1):77-85.

    Article  CAS  PubMed  Google Scholar 

  26. Alexandrine M, Sonia F, Corine V, et al. Porphyrin-aminoquinoline conjugates as telomerase inhibitors. Org Biomol Chem. 2003;1(922):921-7.

    Google Scholar 

  27. Strauss AW, Nunn A, Linder K. Nitroimidazoles for imaging hypoxic myocardium. J Nucl Cardiol. 1995;2:437-45.

    Article  CAS  PubMed  Google Scholar 

  28. Banerjee S, Das T, Samuel G, et al. A novel [186/188Re]-labelled porphyrin for targeted radiotherapy. Nucl Med Commun. 2001;22:1101-7.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are thankful to Miss Yu-qing YANG, Xiao-kun WANG and Mr. Ye-bing LIU (Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, People’s Republic of China) for sample tests and measurements and keen help in radiochemical experiment. The authors also wish to thank Miss Hai-zhen ZHU (MA in Southwest University for Nationalities, People’s Republic China) for her kind support and encouragement in the processing of this paper.

Declaration

The experiments comply with the current laws of China in which we performed inclusive of ethics approval.

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Authors and Affiliations

  1. Department of Nuclear Medicine, West China Hospital, Sichuan University, No.37, Guoxue xiang, Wuhou District, Chengdu, Sichuan Province, 610041, China

    Zhi-yun Jia & Hou-fu Deng

  2. Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang, Sichuan Province, China

    Man-fei Pu & Shun-zhong Luo

Authors
  1. Zhi-yun Jia
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  2. Hou-fu Deng
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  3. Man-fei Pu
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  4. Shun-zhong Luo
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Correspondence to Hou-fu Deng.

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Jia, Zy., Deng, Hf., Pu, Mf. et al. Rhenium-188 labelled meso-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl] porphyrin for targeted radiotherapy: preliminary biological evaluation in mice. Eur J Nucl Med Mol Imaging 35, 734–742 (2008). https://doi.org/10.1007/s00259-007-0682-0

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