Preparation of a 153Sm-5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin complex as a possible therapeutic agent

Document Type : Original Article

Authors

1 Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2 Radiopharmacy Research Group, Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran

3 Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Introduction: Porphyrins are interesting derivatives with low toxicity, tumor avidity and rapid wash-out suggested as potential radiopharmaceuticals in radiolabeled form. In this work we report, synthesis, radiolabeling, quality control, stability, partition coefficient determination and biodistribution studies of 153Sm-5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin (153Sm-4-MPP) in wild-type rats.
Methods: [153Sm]-4MPP was prepared using [153Sm]SmCl3 and 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin (H2-4MPP) for 18 h at 80-90°C. Stability of the complex was checked in final formulation and in presence of human serum for 24 h. The biodistribution of the labeled compound in vital organs of wild-type rats was studied. A detailed comparative pharmacokinetic study performed for 153Sm cation and [153Sm]-4-MPP up to 24h.
Results: The radiochemical purity of [153Sm]-4MPP was reported >97±2% and >99±0.5% by ITLC and HPLC, respectively. The specific activity was 220-230 MBq/mmol. The calculated partition coefficient for the compound was (log P=-1.09). The complex is mostly cleared from the circulation through kidneys and liver. The kidney:blood and  kidney:muscle ratios 24 h post injection were 14.75 and 42.4, respectively.  kidney/liver ratio was almost constant at all time intervals (0.6).

Conclusion: [153Sm]-4MPP was prepared at the optimized conditions and suitable characteristics. Further investigations such as biological studies of this agent on tumor-bearing models are needed.

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Main Subjects

References

Kostova I. Lanthanides as anticancer agents. Curr Med Chem Anticancer Agents. 2005 Nov;5(6):591-602.
Biba F, Groessl M, Egger A, Roller A, Hartinger CG, Keppler BK. New insights into the chemistry of the antineoplastic lanthanum complex tris(1,10-phenanthroline)tris(thiocyanato-κN)lanthanum(III) (KP772) and its interaction with biomolecules. Eur J Inorg Chem. 2009;28:4282-4287.
Thomas SR, Khuntia D. Motexafin gadolinium injection for the treatment of brain metastases in patients with non-small cell lung cancer. Int J Nanomedicine. 2007;2(1):79-87.
Kahl SB, Koo MS. Synthesis and properties of tetrakiscarborane-carboxylate esters of 2, 4-bis (-dihydroxyethyl) deuteroporphyrin IX. In: Allen BJ, Moore DE, Harrington BV (eds). Progress in neutron capture therapy for cancer. New York: Plenum Press; 1992. p. 223-6.
Sasaki K, Yumita N, Nishigaki R, Sakata I, Nakajima S, Umemura SI. Pharmacokinetic study of a gallium-porphyrin photo- and sono-sensitizer, ATX-70, in tumor-bearing mice. Jpn J Cancer Res. 2001 Sep;92(9):989-95.
Fawwaz RA, Frye F, Loughman WD, Hemphill W. Survival of skin homografts in dogs injected with 109Pd-protoporphyrin. J Nucl Med. 1974 Nov;15(11):997-1002.
Fawwaz RA, Hemphill W, Winchell HS. Potential use of 109Pd-porphyrin complexes for selective lymphatic ablation. J Nucl Med. 1971 May;12(5):231-6.
Chakraborty S, Das T, Banerjee S, Sarma HD, Venkatesh M. Preparation and preliminary biological evaluation of a novel 109Pd labeled porphyrin derivative for possible use in targeted tumor therapy. Q J Nucl Med Mol Imaging. 2007 Mar;51(1):16-23.
Sarma HD, Das T, Banerjee S, Venkatesh M, Vidyasagar PB, Mishra KP. Biologic evaluation of a novel 188Re-labeled porphyrin in mice tumor model. Cancer Biother Radiopharm. 2010 Feb;25(1):47-54.
Vahidfar N, Jalilian AR, Fazaeli Y, Bahrami-Samani A, Beiki D, Khalaj A. Development and evaluation of a 166holmium labelled porphyrin complex as a possible therapeutic agent. J Radioanal Nucl Chem. 2012;295(2):979-986.
Pandit-Taskar N, Batraki M, Divgi CR. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med. 2004 Aug;45(8):1358-65.
Naseri Z, Hakimi A, Jalilian AR, Kharat AN, Shirvani-Arani S, Bahrami-Samani A, Ghannadi-Maragheh M. Synthesis, quality control and biological evaluation of tris[(1,10-phenanthroline)[153Sm]samarium(III)]trithiocyanate complex as a therapeutic agent.  Radiochimica Acta. 2012;100:267-272.
Bahrami-Samani A, Ghannadi-Maragheh M, Jalilian AR, Mazidi M. Biological studies of samarium-153 bleomycin complex in human breast cancer murine xenografts for therapeutic applications. Radiochimica Acta. 2010;98(4):237-242.
Bahrami-Samani A, Jalilian AR, Yousefnia H, Akhlaghi M, Mazidi M, Ghannadi-Maragheh M. Development of Sm-153 chitosan for radiosynovectomy. Iran J Nucl Med. 2010;18(1):22-31.
Fani M, Xanthopoulos S, Archimandritis SC, Stratis N, Bouziotis P, Loudos G, Varvarigou AD.Biodistribution and scintigraphic studies of 153Sm-labeled anti-CEA monoclonal antibody for radioimmunoscintigraphy and radioimmunotherapy. Anticancer Res. 2003 May-Jun;23(3A):2195-9.
Radfar E, Jalilian AR, Yousefnia H, Bahrami-Samani A, Ghannadi-Maragheh M. A comparative study of preliminary dosimetry for human based on distribution data in rats with 111In, 90Y, 153Sm, and 177Lu labeled rituximab. Nucl Technol Radiat. 2012;27(2):144-151.
Falk JE. Porohyrins and metalloporphyrins. New York: Elsevier Science Publishing; 1975.
International Atomic Energy Agency. Manual for reactor produced radioisotopes. Vienna: IAEA; 2003. p.71.
Adler AD, Longo FR, Finarelli JD, Goldmacher J, Assour J, Korsakoff L. A simplified synthesis for meso-tetraphenylporphine. J Org Chem. 1967;32(2):476.
Jalilian AR, Rowshanfarzad P, Sabet M, Novinrooz A, Raisali G. Preparation of [66Ga]bleomycin complex as a possible PET radiopharmaceutical. J Radioanal Nucl Chem 2005; 264(3):617-621.
Naseri Z, Jalilian AR, Kharat AN, Bahrami-Samani A, Ghannadi-Maragheh M. Production, quality control and biological evaluation of 153Sm-TTHMP as a possible bone palliation agent. Iran J Nucl Med. 2011;19(2):60-68.
Kobuchi H, Moriya K, Ogino T, Fujita H, Inoue K, Shuin T, Yasuda T, Utsumi K, Utsumi T. Mitochondrial localization of ABC transporter ABCG2 and its function in 5-aminolevulinic acid-mediated protoporphyrin IX accumulation. PLoS One. 2012;7(11):e50082.
Paknafas A, Fazaeli Y, Jalilian AR, Ahmadi A, Feizi S, Kamalidehghan M, Rahiminejad A, Khalaj A. Radiosynthesis and Quality Control of [(67)Ga]-3,4-dimethoxylated Porphyrin Complex as a Possible Imaging agent. Iran J Pharm Res. 2013 Fall;12(4):735-44.
With TK. Micro-estimation of porphyrins in bones, teeth and shells. Biochem J. 1955 Aug;60(4):703-4.
Iranian Journal of Nuclear Medicine
Volume 23, Issue 2 - Serial Number 44
Serial number: 44
July 2015
Pages 65-72

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