Synthesis, characterization and in vivo evaluation of [62Zn]–benzo-δ-sultam complex as a possible pet imaging agent
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The development of a new tracer based on the cyclic sulfonamides (sultams) was investigated.
3-(Methoxy-phenyl-methyl)-1,6-dimethyl-1H benzo[c][1,2] thiazine 2,2-dioxide (benzo-δ-sultam) was synthesized and characterized by elemental analysis, FT-IR spectroscopy and single crystal X-ray structure determination. The prepared cyclic sulfonamide was labeled with non-commercial 62Zn radioisotope for fast in vivo targeting and Coincidence imaging purposes (radiochemical purity 97 % ITLC, 96 % HPLC, specific activity 20–23 GBq/mmol). In vivo biodistribution of the final complex was investigated in Sprague Dawley® rats bearing fibro sarcoma tumor after 2, 4 and 8 h post injection and compared with free Zn+2 cation.
Using instant paper chromatography method, the physicochemical properties of labeled compounds were found sufficiently stable in organic phases, e.g. a human serum, to be reliably used in bioapplications.
The complex exhibited a rapid as well as high tumor uptake (tumor to blood ratio 4.38 and tumor to muscle ratio 9.63) resulting in an efficient tumor targeting agent.
Keywords62Zn production Benzo-δ-sultam Coincidence imaging Bio distribution
Conflict of interest
The authors report no conflicts of interest in this work.
- 3.Piel H, Qai SM, Stöcklin G. Excitation functions of (p, xn)-reactions on natNi and highly enriched 62Ni: possibility of production of medically important radioisotope 62Cu at a small cyclotron. Radiochim Acta. 1992;57:1–5.Google Scholar
- 7.Jalilian AR, Fateh B, Ghergherehchi M, Karimian A. Development of [62Zn] bleomycin as a possible PET tracer. Nukleonika. 2005;50:143–8.Google Scholar
- 12.Lacy JL, Chien SC, Lim JK, Mathias CJ, Green MA. Modular automated Zn-62/Cu-62 PET radiopharmaceutical generator. J Nucl Med. 1995;36:49.Google Scholar
- 13.Matsumoto K, Fujibayashi Y, Yonekura Y. Application of the new zinc-62/copper-62 generator: An effective labeling method for Cu-PTSM. Nucl Med Biol. 1992;19(1):39–44.Google Scholar
- 17.Inagaki M, Tsuri T, Jyoyama H, Ono T, Yamada K, Kobayashi M, Hori Y, Arimura A, Yasui K, Ohno K, Kakudo S, Koizumi K, Suzuki R, Kato M, Kawai S, Matsumoto S. Novel antiarthritic agents with 1,2-isothiazolidine-1,1-dioxide (γ-sultam) skeleton: cytokine suppressive dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase. J Med Chem. 2000;43(10):2040–8.PubMedCrossRefGoogle Scholar
- 20.McKeown SC, Hall A, Blunt R, Brown SH, Chessell IP, Chowdhury A, Giblin GMP, Healy MP, Johnson MR, Lorthioir O, Michel AD, Naylor A, Lewell X, Roman S, Watson SP, Winchester WJ, Wilson RJ. Identification of novel glycine sulfonamide antagonists for the EP1 receptor. Bioorg Med Chem Lett. 2007;17(6):1750–4.PubMedCrossRefGoogle Scholar
- 21.Council Biological. Guidelines on the use of living animals in scientific investigations. 2nd ed. London: Biological Council; 1987.Google Scholar
- 22.Weisberg AM. Gold plating. 9th ed. USA: ASM International; 1990. p. 247.Google Scholar
- 23.The crystallographic information file has been deposited with the Cambridge Data Centre, CCDC 974372.Google Scholar
- 24.X-STEP32 Version 1.07b, Crystallographic Package; Stoe & Cie GmbH: Darmstadt, Germany, 2000.Google Scholar
- 28.Reference charged particle cross-section database for medical radioisotope production, Diagnostic radio isotopes and monitor reactions IAEA-TECDOC-1211, IAEA, Vienna, Austria, 2001.Google Scholar