Journal of Nuclear Science, Engineering and Technology (JONSAT)
In cooperation with the Iranian Nuclear Society

Production and Evaluation of Lutetium-177 Maltolate as a Possible Therapeutic Agent

Document Type : Research Paper

Authors

A Hakimi
A.R. Jalilian
A Bahrami Samani
M Ghannadi Maragheh
Abstract
Development of oral therapeutic radiopharmaceuticals is a new concept in radiopharmacy. Due to the interesting therapeutic properties of 177Lu and oral bioavailability of maltolate (MAL) metal complexes, 177Lu-maltolate (177Lu-MAL) was developed as a possible therapeutic compound for ultimate oral administration. The specific activity of 2.6-3 GBq/mg was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4×1013 n.cm-2.s-1 for Lu-177. The product was converted into chloride form which was further used for labeling maltol (MAL). At optimized conditions a radiochemical purity of about >99% was obtained for 177Lu-MAL shown by ITLC (specific activity, 970-1000 Mbq/mmole). The stability of the labeled compound as well as the partition coefficient was determined in the final solution up to 24h. Biodistribution studies of Lu-177 chloride and 177Lu-MAL were carried out in wild-type rats for post-oral distribution phase data. Lu-MAL is a possible therapeutic agent in human malignancies for the bone palliation therapy so the efficacy of the compound should be tested in various animal models.
 

Highlights

  1. R.B. Firestone, V.S. Shirley, C.M. Baglin, J. Zipkin, “In: table of isotopes,” 8th Edition, John Wiley and Sons, 1447, New York (1996).

     

  2. T. Das, “Lu-EDTMP: a new radiopharmaceutical for palliation of bone in cancer skeletal metastases,” Dr. Homi Bhabha Centenary Year, Issue No. 305, 2-11 (2009).

 

  1. L.R. Bernstein, T. Tanner, C. Godfrey, B. Noll, “Chemistry and Pharmacokinetics of Gallium Maltolate, a compound with high oral Gallium Bioavailability,” Metal Based Drugs. 7: 33-48 (2000).

 

  1. C.R. Chitambar, D.P. Purpi, J. Woodliff, M. Yang, J.P. Wereley, “Development of Gallium Compounds for Treatment of Lymphoma: Gallium Maltolate, a Novel Hydroxypyrone Gallium Compound, Induces Apoptosis and Circumvents Lymphoma Cell Resistance to Gallium Nitrate, J. Pharm Exp Ther.  322:1228-1236 (2007).

 

  1. C.R. Chitambar, “Gallium nitrate for the treatment of non-Hodgkin’s lymphoma,” Expert Opin Invest Drugs, 13:531-541 (2004).

 

  1. B. Pro, R.G. Bociek, C.R. Chitambar, S.A. Gregory, J.P. Leonard, S. Smith, S. Novick, “Phase 2 multicenter trial of gallium nitrate in patients with advanced non-Hodgkin’s lymphoma (NHL),” Blood, 104: 682A (2004).

 

  1. L.R. Bernstein, T. Trevor Tanner, C. Claire Godfrey, B. Bruce Noll, “Chemistry and pharmacokinetics of gallium maltolate,” A Compound with High Oral Gallium Bioavailability Metal-Based Drugs, 7:33-47 (2000).

  2. R.J. Martens, K. Mealey, N.D. Cohen, J.R. Harrington, M.K. Chaffin, R.J. Taylor, L.R. Bernstein, “Pharmacokinetics of gallium maltolate after intragastric administration in neonatal foals,” Am. J. Vet Res. 68:1041-4 (2007).

 

  1. E. Satoh, I. Yasuda, T. Yamada, Y. Suzuki, T. Ohyashiki, “Involvement of no generation in aluminum-induced cell death biol pharm bull,” 30:1390-1394 (2007).

 

  1. K. DeLeon, F. Balldin, C. Watters, A. Hamood, J. Griswold, S. Sreedharan, K.P. Rumbaugh, “Gallium maltolate treatment eradicates pseudomonas aeruginosa infection in thermally injured mice,” Antimicr Agents Chemother. 1331–1337 (2009).

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  1. A. Barve, A. Kumbhar, M. Bhat, B. Joshi, R. Butcher, U. Sonawane, R. Joshi, “Mixed-ligand copper(II) maltolate complexes: synthesis, characterization, DNA binding and cleavage, and cytotoxicity,” Inorg Chem. 48:9120-32 (2009).

 

  1. Manual for Reactor Produced Radioisotopes, IAEA, Vienna, IAEA-TECDOC-1340, ISBN 92–0–101103–2, ISSN 1011–4289, IAEA, 2003, 121-123, Printed by the IAEA in Austria, (January 2003).

Keywords

Maltolate
Lu-177
Biodistribution
Radiolabeling

  1. R.B. Firestone, V.S. Shirley, C.M. Baglin, J. Zipkin, “In: table of isotopes,” 8th Edition, John Wiley and Sons, 1447, New York (1996).

     

  2. T. Das, “Lu-EDTMP: a new radiopharmaceutical for palliation of bone in cancer skeletal metastases,” Dr. Homi Bhabha Centenary Year, Issue No. 305, 2-11 (2009).

 

  1. L.R. Bernstein, T. Tanner, C. Godfrey, B. Noll, “Chemistry and Pharmacokinetics of Gallium Maltolate, a compound with high oral Gallium Bioavailability,” Metal Based Drugs. 7: 33-48 (2000).

 

  1. C.R. Chitambar, D.P. Purpi, J. Woodliff, M. Yang, J.P. Wereley, “Development of Gallium Compounds for Treatment of Lymphoma: Gallium Maltolate, a Novel Hydroxypyrone Gallium Compound, Induces Apoptosis and Circumvents Lymphoma Cell Resistance to Gallium Nitrate, J. Pharm Exp Ther.  322:1228-1236 (2007).

 

  1. C.R. Chitambar, “Gallium nitrate for the treatment of non-Hodgkin’s lymphoma,” Expert Opin Invest Drugs, 13:531-541 (2004).

 

  1. B. Pro, R.G. Bociek, C.R. Chitambar, S.A. Gregory, J.P. Leonard, S. Smith, S. Novick, “Phase 2 multicenter trial of gallium nitrate in patients with advanced non-Hodgkin’s lymphoma (NHL),” Blood, 104: 682A (2004).

 

  1. L.R. Bernstein, T. Trevor Tanner, C. Claire Godfrey, B. Bruce Noll, “Chemistry and pharmacokinetics of gallium maltolate,” A Compound with High Oral Gallium Bioavailability Metal-Based Drugs, 7:33-47 (2000).

  2. R.J. Martens, K. Mealey, N.D. Cohen, J.R. Harrington, M.K. Chaffin, R.J. Taylor, L.R. Bernstein, “Pharmacokinetics of gallium maltolate after intragastric administration in neonatal foals,” Am. J. Vet Res. 68:1041-4 (2007).

 

  1. E. Satoh, I. Yasuda, T. Yamada, Y. Suzuki, T. Ohyashiki, “Involvement of no generation in aluminum-induced cell death biol pharm bull,” 30:1390-1394 (2007).

 

  1. K. DeLeon, F. Balldin, C. Watters, A. Hamood, J. Griswold, S. Sreedharan, K.P. Rumbaugh, “Gallium maltolate treatment eradicates pseudomonas aeruginosa infection in thermally injured mice,” Antimicr Agents Chemother. 1331–1337 (2009).

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  1. A. Barve, A. Kumbhar, M. Bhat, B. Joshi, R. Butcher, U. Sonawane, R. Joshi, “Mixed-ligand copper(II) maltolate complexes: synthesis, characterization, DNA binding and cleavage, and cytotoxicity,” Inorg Chem. 48:9120-32 (2009).

 

  1. Manual for Reactor Produced Radioisotopes, IAEA, Vienna, IAEA-TECDOC-1340, ISBN 92–0–101103–2, ISSN 1011–4289, IAEA, 2003, 121-123, Printed by the IAEA in Austria, (January 2003).

Journal of Nuclear Science, Engineering and Technology (JONSAT)
Volume 33, Issue 2 - Serial Number 60
September 2012
Pages 61-67

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