99mTc-labeled sigma-receptor-binding complex: synthesis, characterization, and specific binding to human ductal breast carcinoma (T47D) cells

Bioconjugate Chemistry
C S JohnW D Bowen

Abstract

sigma-Receptors have recently been shown to be expressed in a variety of human tumor cells. In an attempt to prepare 99mTc chelates that would bind to sigma-receptors and be useful for imaging sigma-receptor-positive tumors, we have synthesized and characterized a bisaminothiol (BAT) chelate appended with a sigma-receptor pharmacophore. The synthesis of target ligand VII was accomplished in three steps starting from bicyclic imidazolidino[1,2-d]dithiazapine. The labeling of the BAT ligand with 99mTc was carried out in high yields (> 80%) using stannous tartarate as a reducing agent, resulting in the target sigma-receptor-binding chelate [99mTc]BAT-EN6, III. Similarly, 99gTc chelate with ligand VII was prepared from ammonium pertechnetate by reduction with stannous tartarate. 99nTc-radiolabeled chelate was purified by reversed phase HPLC, and cell binding with human breast ductal carcinoma (T47D) was performed. A high degree of specific binding (90-97%) was obtained when sigma-receptor ligands such as halogenated phenylethylenediamines were used to determine nonspecific binding. A modest affinity dose-dependent inhibition of binding was found with BD1008, I, and 4-IPEMP, II (IC50 = 47 +/- 2 and 59 +/- 5 nM, respectively), known ...Continue Reading

Citations

May 17, 2000·Pharmaceutica acta Helvetiae·W D Bowen
Jun 6, 2013·Journal of Medicinal Chemistry·Robert H MachWilliam G Hawkins
Jan 7, 1999·Breast Cancer Research and Treatment·J S StroblH Hylton
Apr 17, 2001·European Journal of Nuclear Medicine·V CaveliersA Bossuyt
Jun 10, 2015·Journal of Receptor and Signal Transduction Research·Colin G Rousseaux, Stephanie F Greene
Sep 1, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bieke Van Den Bossche, Christophe Van de Wiele
Apr 8, 2010·Human Psychopharmacology·Ian Hindmarch, Kenji Hashimoto
Aug 8, 2013·Medicinal Research Reviews·Yun-Sheng HuangZongwen Wu
Aug 4, 2004·Cancer Research·Ebru AydarMustafa B A Djamgoz
Dec 26, 2001·Chemical Reviews·S S Jurisson, J D Lydon

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