Preliminary Dosimetric Evaluation of a New Therapeutic 177Lu Complex for Human Based on Biodistribution Data in Rats
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.
[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.
[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.
@article{"International Journal of Biological, Life and Agricultural Sciences:71271", author = "H. Yousefnia and S. Zolghadri and A. Golabi Dezfuli", title = "Preliminary Dosimetric Evaluation of a New Therapeutic 177Lu Complex for Human Based on Biodistribution Data in Rats", 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.", volume = "9", number = "9", pages = "1024-5", }
