Preparation and quality control of scandium-46 bleomycin as a possible therapeutic agent

Document Type : Original Article

Authors

Radiopharmaceutical Research and Development Lab (RRDL), Nuclear Science and Technology Research Institute (NSTRI), Atomic Energy Organization of Iran, Tehran, Iran

Abstract

Introduction: Due to interesting therapeutic properties of 46Sc and antineoblastic antibiotic, bleomycin (BLM), 46Sc-bleomycin (46Sc-BLM) was developed as a possible therapeutic compound.
Methods: In this work, Sc-46 chloride was obtained by thermal neutron flux (4 × 1013 n.cm-2.s-1) of natural metallic scandium sample followed by dissolution in acidic media  as a substitute for 47Sc in radiolabeling studies which was further used for labeling of bleomycin (BLM) followed by stability studies as well as biodistribution in wild-type rats.
Results:  Sc-46 was obtained in high radiochemical purity (ITLC, >99%, two systems) as well as acceptable specific activity. At optimized conditions a radiochemical purity of 98% was obtained for 46Sc-BLM shown by ITLC (Specific activity, 740 GBq/mmole). The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled bleomycins.

Conclusion: Sc-BLM is a possible therapeutic agent in human malignancies and the efficacy of the compound should be tested in various tumor-bearing models.

Keywords

Main Subjects

References

Firestone RB, Shirley VS. Table of Isotopes. 8th Edition, New York: John Wiley & Sons Inc.; 1996. P. 1534-1536, 1545.
Cann CE, Prussin SG. Possible parathyroid imaging using Ga-67 and other aluminum analogs. J Nucl Med. 1980 May;21(5):471-4.
Ahn JY, Lee DS, Lee JS, Kim SK, Cheon GJ, Yeo JS, Shin SA, Chung JK, Lee MC. Quantification of regional myocardial blood flow using dynamic H2(15)O PET and factor analysis. J Nucl Med. 2001 May;42(5):782-7.
Audibert G, Saunier CG, Siat J, Hartemann D, Lambert J. Effect of the inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester, on cerebral and myocardial blood flows during hypoxia in the awake dog.  Anesth Analg. 1995 Nov;81(5):945-51.
Miller JK, Byrne WF. Comparison of scandium-46 and cerium-144 as nonabsorbed reference materials in studies with cattle. J Nutr. 1970 Nov;100(11):1287-91.
Umezawa H, Takeuchi T, Hori S, Sawa T, Ishizuka M. Studies on the mechanism of antitumor effect of bleomycin of squamous cell carcinoma. J Antibiot (Tokyo). 1972 Jul;25(7):409-20.
Korppi-Tommola T, Huhmar H, Aronen HJ, Penttilä P, Hiltunen J, Savolainen S, Kallio ME, Liewendahl K. 111In-labelled bleomycin complex for the differentiation of high- and low-grade gliomas. Nucl Med Commun. 1999 Feb;20(2):145-52.
Melnyk DL, Horwitz SB, Peisach T. The oxidation-reduction potential of copper-bleomycin. Inorgan Chim Acta. 1987;138:75-78.
Lenkinski RE, Peerce BE, Pillai RP, Glickson JD. Calcium(II) and the trivalent lanthanide ion complexes of the bleomycin antibiotics. Potentiometric, fluorescence and proton NMR studies. J Am Chem Soc. 1980;102:7088–93.
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. Radiochim Acta. 2010;98:237-42.
Stern PH, Helpern SE, Hagan PL, Howell SB, Dabbs JE, Gordon RM. Cytotoxic activity, tumor accumulation, and tissue distribution of ruthenium-103-labeled bleomycin. J Natl Cancer Inst. 1981 May;66(5):807-11.
Brooks RC, Carnochan P, Vollano JF, Powell NA, Zweit J, Sosabowski JK, Martellucci S, Darkes MC, Fricker SP, Murrer BA. Metal complexes of bleomycin: evaluation of [Rh-105]-bleomycin for use in targeted radiotherapy. Nucl Med Biol. 1999 May;26(4):421-30.
Jalilian AR, Akhlaghi M, Shirazi B, Aboudzadeh R, Raisali G, Salouti M, Babaii M. [201Tl](III)-bleomycin for tumor imaging. Radiochim Acta. 2006;94(8):453-9.
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;264:617-21.
Jalilian AR, Fateh B, Ghergherehchi M, Karimian A. Development of [62Zn]bleomycin as a possible PET tracer. Nukleonika. 2005;50:143-148.
Jalilian AR, Zandi H, Sardari D, Akhlaghi M, Rowshanfarzad P, Saddadi F, Majdabadi A. Preparation and biological evaluation of [Cu-61]bleomycin complex as a possible PET radiopharmaceutical. Nukleonika. 2009;54:135−41.
Reynolds JE. Martindale: The extra pharmacopoeia. 31st ed., London: Royal Pharmaceutical Society; 1996. P. 546-7.
Takita T, Umezawa Y, Saito SI, Morishima H, Naganawa H, Umezawa H, Tsuchiya T, Miyake T, Kageyama S, Umezawa S, Muraoka Y, Suzuki M, Otsuka M, Narita M, Kobayashi S, Ohno M. Retro-synthetic manipulation of bleomycins. Tet Lett. 1982;123:521-4.
Ford-Hutchinson AW, Perkins DJ. 46 Scandium metabolism; binding to metalloproteins in vivo and in vitro. Radiat Res. 1972 Aug;51(2):244-8.
Lachine EE, Noujaim AA, Ediss C, Wiebe LI. Toxicity, tissue distribution and excretion of 46ScCl3 and 46Sc-EDTA in mice. Int J Appl Radiat Isot. 1976 Jul;27(7):373-7.
Iranian Journal of Nuclear Medicine
Volume 20, Issue 1 - Serial Number 37
Serial number: 37
December 2012
Pages 19-24

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