- Preparation and biodistribution of technetium-99m-labeled bis-misonidazole (MISO) as an imaging agent for tumour hypoxia
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Diagnosis of tumour hypoxia is an important aspect in determining the course of tumour therapy. In this study, we developed a novel imaging agent, 99mTcethylenedicysteine-bis-misonidazole (99mTc-EC-MISO), for diagnosing tumour hypoxia. We used 2-nitroimidazole as a reactant to synthesize the amino derivative of misonidazole (MISO) in the first step and then conjugated the di-amino derivative of MISO to the chelating agent ethylenedicysteine (EC) for labelling 99mTc in the second step. 99mTc-pertechnetate (99mTcO4-) was reduced by tin chloride (SnCl2) for radiolabeling. The radiochemical purity was up to 94%. Tissue biodistribution and SPECT/CT imaging studies were conducted on subcutaneous gliomal tumour-bearing mice. The tumour-to-muscle ratio in the 99mTc-EC-MISO group increased with time, up to 4.6 at 4 h after injection. SPECT/CT imaging confirmed that the tumours could be visualized clearly with 99mTc-EC-MISO at 2 h. By introducing a second 2-nitroimidazole redox centre, an apparent hypoxic accumulation of this novel 99mTc-labeled imaging agent in the tumour was observed.
- Wang, Feng,Fan, Di,Qian, Jun,Zhang, Zhe,Zhu, Jianhua,Chen, Jian
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p. 649 - 655
(2015/12/01)
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- Hypoxia-selective, weakly basic 2-nitroimidazole delivery agents and methods of use thereof
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The invention features a class of 2-nitroimidazole compounds with a secondary basic nitrogen atom and a linker bearing one or more therapeutic agents, cytotoxic agents, detectable labels, or chelating groups. In particular, the invention provides 2-nitroimidazole compounds containing a cluster of boron atoms for use in boron neutron capture therapy (BNCT). The 2-nitroimidazole compounds can be used to treat hypoxic conditions, including, e.g., cancer, inflammation, and ischemia. The weakly basic 2-nitroimidazole compounds target to hypoxic tissue and provide increased tissue concentration overall.
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Page/Page column 14; 17
(2008/06/13)
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- Radiopharmaceutical formulations
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A method is described for inhibiting the degradation of a diagnostic or radiotherapeutic radiopharmaceutical, especially radiolabeled compounds containing reducible moieties, by including oxidants either as a part of the composition for the preparation of such radiopharmaceuticals, or by adding an oxidant to such compositions immediately after the preparation of such radiopharmaceuticals.
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Page/Page column 6
(2008/06/13)
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- Heteroatom-bearing ligands and metal complexes thereof
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Novel compounds containing a heteroatom-bearing bridge and novel complexes of these compounds with metals. The novel compounds and complexes are useful in diagnostic and therapeutic methods.
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- Radiosensitizers of hypoxic mammalian cells. 1-(hydroxyaminoalkyl)-substituted nitroimidazoles
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A series of novel 1-(hydroxyaminoalkyl)-substituted nitroimidazoles has been synthesized as potential radiosensitizers for hypoxic mammalian cells. These compounds were synthesized via N-(hydroxyalkyl)phthalimide nitroimidazole intermediates which, on reaction with hydrazine hydrate, yielded the corresponding amines. The intermediates were prepared by reacting the epoxide derived from nitroimidazole with phthalimide and/or the epoxide derived from phthalimide with the nitroimidazole. The method was used successfully for the preparation of 2-, 4- and 5-nitroimidazole derivatives. In a modification of this procedure, 1-(2-aminoethyl)-2-nitroimidazole has been prepared by a new route which avoids the use of aziridine. These agents were tested for cytotoxicity and radiosensitizing ability in vitro using Chinese hamster V79 cells. All of the 2-nitroimidazoles tested showed toxicity similar to that previously reported for misonidazole and Ro 03-8799 (1-(2-hydroxy-3-piperidinopropyl)-2-nitroimidazole), two compounds currently undergoing clinical evaluation. In addition, all the novel primary amines were shown to function as hypoxic cell radiosensitizers. The 2-nitroimidazole derivatives were the most efficient compounds to be examined and showed at least as much activity as misonidazole.
- Ahmed,Stratford,Jenkins
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p. 1763 - 1768
(2007/10/02)
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