Preliminary Dosimetric Evaluation of a New Therapeutic 177Lu Complex for Human Based on Biodistribution Data in Rats

Authors: H. Yousefnia, S. Zolghadri, A. Golabi Dezfuli

Abstract:

Abstract—[Tris (1,10-phenanthroline) lanthanum(III)] trithiocyanate is a new compound that has shown high ability for stopping the synthesis of DNA and also acting as a photosensitizer. Nowadays, the radiation dose assessment resource (RADAR) method is known as the most common method for absorbed dose calculation. 177Lu was produced by (n, gamma) reaction in a research reactor. 177Lu-PL3 was prepared in the optimized condition. The radiochemical yield was checked by ITLC method. The biodistribution of the complex was investigated by intravenously injection to wild-type rats via their tail veins. In this study, the absorbed dose of 177Lu-PL3 to human organs was estimated by RADAR method. 177Lu was prepared with a specific activity of 2.6-3 GBq.mg-1 and radionuclide purity of 99.98 %. Final preparation of the radiolabelled complex showed high radiochemical purity of > 99%. The results show that liver and spleen have received the highest absorbed dose of 1.051 and 0.441 mSv/MBq, respectively. The absorbed dose values for these two dose-limiting tissues suggest more biological studies special in tumor-bearing animals.

Keywords: Internal dosimetry, Lutetium-177, radar.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1109776

References:

[1] S. Neidle, "The molecular basis for the action of some DNA-binding drugs," Prog. Med. Chem., vol. 16, pp. 151-221, 1979.
[2] W. B. Pratt, R. W. Ruddon, "The Anticancer Drugs" Oxford University Press: London, 1979.
[3] Y. B. Zeng, N. Yang, W. S. Liu, N. Tang, "Synthesis, characterization and DNA-binding properties of La(III) complex of chrysin" J. Inorg. Biochem., vol. 97, no. 3, pp. 258–64, Nov. 2003.
[4] T. B. Kovachev, D. S. Ivanov, R. T. Buyukliev, S. M. Konstantinov, M. C. Karaivanova, "Synthesis and tumor inhibiting activity of lanthanum(III) complexes with some 1-aminocycloalkancarboxylic acids," Pharmazie, vol. 51, no. 1, pp. 25-7, Jan. 1996.
[5] Z. M. Wang, H. K. Lin, S. R. Zhu, T. F. Liu, Z. F. Zhou, Y. T. Chen, "Synthesis, characterization and cytotoxicity of lanthanum(III) complexes with novel 1,10-phenanthroline-2,9-bis-alpha-amino acid conjugates," Anticancer Drug Des, vol. 15, no. 6, pp.405-11, Dec. 2000.
[6] Z. M. Wang, H. K. Lin, S. R. Zhu, T. F. Liu, Y. T. Chen, "Spectroscopy, cytotoxicity and DNA-binding of the lanthanum(III) complex of an Lvaline derivative of 1,10-phenanthroline," J Inorg Biochem. Vol. 89, pp. 97–106, 2002.
[7] K. H. Falchuk, A. Krishan, "1,10-Phenanthroline inhibition of lymphoblast cell cycle," Cancer Res. vol. 37, no. 7 Pt 1, pp. 2050-6, Jul. 1977.
[8] C. Krishnamurti, L. A. Saryan, D. H. Petering, "Effects of ethylenediaminetetraacetic acid and 1,10-phenanthroline on cell proliferation and DNA synthesis of Ehrlich ascites cells," Cancer Res. vol. 40, no. 11, pp. 4092-9, Nov. 1980.
[9] P. Heffeter, M. A. Jakupec , W. Körner, S. Wild, N. G. von Keyserlingk, L. Elbling, H. Zorbas, A. Korynevska, S. Knasmüller, H. Sutterlüty, M. Micksche, B. K. Keppler, W. Berger, "Anticancer activity of the lanthanum compound (tris(1,10- phenanthroline)lanthanum(III))trithiocyanate (KP772; FFC24)," Biochem Pharmacol, vol. 1471, no. 4, pp. 426-40, Feb. 2006.
[10] P. G. Sammes, G. Yahioglu, "1,10-Phenanthroline: A Versatile Ligand," Chem Soc Rev, vol. 23, pp. 327–334, 1994.
[11] W. D. McFadyen, L. P. Wakelin, I. A. Roos, V. A. Leopold, "Activity of platinum(II) intercalating agents against murine leukemia L1210," J Med Chem, vol. 28, no. 8, pp. 1113-6, Aug. 1985.
[12] H. Yousefnia, A. R. Jalilian, S. Zolghadri, A. Bahrami-Samani, S. Shirvani-Arani, M. Ghannadi-Maragheh, "Preparation and quality control of 177Lu-(tris(1,10-phenanthroline) lutetium(III)) complex for therapy" Nucl. Med. Rev., vol. 13, no. 2, pp. 49–54, 2010.
[13] M. G. Stabin, M. Tagesson, S. R. Thomas, M. Ljungberg, S. E. Strand, "Radiation dosimetry in nuclear medicine," Appl. Radiat. Isot., vol. 50, no. 1, pp. 73-87, Jan. 1999.
[14] M. G. Stabin, J. A. Siegel, "Physical Models and Dose Factors for Use in Internal Dose Assessment," Health Phys., vol. 85, no. 3, pp. 294-310, Sep. 2003.
[15] IAEA-TECDOC-1340, "Manual For Reactor Produced Radioisotopes, International Atomic Energy Agency (IAEA)," ISBN 92–0–101103–2, ISSN 1011–4289, Printed by the IAEA in Austria, VIENNA, January 2003.
[16] R. B. Sparks, B. Aydogan, "Comparison of the effectiveness of some common animal data scaling techniques in estimating human radiation dose. Sixth International Radiopharmaceutical Dosimetry Symposium," Oak Ridge, TN: Oak Ridge Associated Universities. pp. 705–716, 1996.
[17] J. J. Bevelacqua, "Internal dosimetry primer," Radiat. Prot. Manage., vol. 22, no. 5, pp. 7-17, 2005.
[18] OLINDA - Organ Level Internal Dose Assessment Code (Version 1.1), Copyright Vanderbilt University, 2007.