Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers

Hoigebazar, Lathika; Jeong, Jae Min; Hong, Mee Kyung; Kim, Young Ju; Lee, Ji Youn; Shetty, Dinesh; Lee, Yun Sang; Lee, Dong Hoon; Chung, June Key; Lee, Myung Chul

doi:10.1016/j.bmc.2011.02.041

Cited by 50 publications

(51 citation statements)

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“…The uptake ratios for 68 2.3,and 1.6 at 15,30,and 60 min, respectively; in CT-26 cells they were 1.0, 1.5, and 3.0 at 15, 30, and 60 min, respectively. The uptake ratios for Ga-6 showed higher hypoxic-to-normoxic uptake ratios than the reported agents such as 68 Ga-NOTA-NI (1.5), 68 Ga-NOTA-SCN-NI (2.6), 68 Ga-DOTA-NI (6.8), and 68 Ga-DOTA-SCN-NI (3.4) at 60 min time point in CT-26 cell lines [53,54].…”

Section: -3mentioning

confidence: 64%

“…Moreover, protection is not required before conjugation with ligands by amide formation [48,58]. The nitroimidazole residue, 2-(2-nitroimidazolyl)ethylamine hydrochloride was also synthesized according to a previously published method [53,54].…”

Section: -1 Synthesismentioning

confidence: 99%

“…Radiochemical purities of the 68 Ga labeled conjugates were measured by radio-HPLC, and found to be greater than 99%. The 68 Ga-labeled derivatives showed low partition coefficients (log P), indicating that all are very hydrophilic ( Ga-DOTA-SCN-NI (14.04 ± 0.49) at 60 min time point [53,54], which might favor rapid uptake by target tissues and rapid clearance from blood and non-target tissues. Furthermore, all showed high in vitro stability, up to 4 h in prepared media at room temperature and in human serum at 37 °C (Figure 2 -4).…”

Section: -2 Radiochemistrymentioning

confidence: 99%

“…Although nitroimidazole derivatives conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for 68 Ga labeling have been reported, NOTA-nitroimidazole conjugates have shown higher tumor-to-muscle standard uptake value (SUV) ratios than DOTAnitroimidazole derivatives [53,54]. Tc have been reported and showed improved biodistribution [56,57].…”

Section: Introductionmentioning

confidence: 99%

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Development of 68Ga-labeled multivalent nitroimidazole derivatives for hypoxia imaging

Seelam

Lee

et al. 2015

Bioorganic & Medicinal Chemistry

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Section: -3mentioning

confidence: 64%

Section: -1 Synthesismentioning

confidence: 99%

Section: -2 Radiochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of 68Ga-labeled multivalent nitroimidazole derivatives for hypoxia imaging

Seelam

Lee

et al. 2015

Bioorganic & Medicinal Chemistry

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“…Therefore, 68 Ga-labeled PET probes possess significant commercial potential and serve as a convenient alternative to cyclotron-based PET radionuclides, such as 18 F. For hypoxic imaging, 68 Ga-labeled nitroimidazole derivatives were recently reported. 28,29) To produce the shortlived 68 …”

mentioning

confidence: 99%

In Vivo Evaluation of a Radiogallium-Labeled Bifunctional Radiopharmaceutical, Ga-DOTA-MN2, for Hypoxic Tumor Imaging

Sano

Okada

Hisada

et al. 2013

Biological & Pharmaceutical Bulletin

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On the basis of the findings obtained by X-ray crystallography of Ga-DOTA chelates and the drug design concept of bifunctional radiopharmaceuticals, we previously designed and synthesized a radiogalliumlabeled DOTA chelate containing two metronidazole moieties, 67Ga-DOTA-MN2, for hypoxic tumor imaging. As expected, 67Ga-DOTA-MN2 exhibited high in vivo stability, although two carboxyl groups in the DOTA skeleton were conjugated with metronidazole moieties. In this study, we evaluated 67/68 Ga-DOTA-MN2 as a nuclear imaging agent for hypoxic tumors. Key words radiogallium; bifunctional radiopharmaceutical; hypoxic tumor imaging; positron emission tomography Tumor hypoxia results from an imbalance between oxygen supply and consumption, which is caused by abnormal structure and function of microvessels supplying the tumor, increased diffusion distances between the nutritive blood vessels and the tumor cells, and reduced O 2 transport capacity of the blood.1,2) Tumor hypoxia has been associated with an aggressive tumor phenotype, poor response to radiotherapy and chemotherapy, and increased risk of invasion and metastasis of tumors.3,4) Thus, non-invasive measurement of tumor hypoxia with positron emission tomography (PET) would have a distinct effect on characterizing tumor malignancy and determining a course of therapy.Metronidazole, nitroimidazole antibiotic medication used for anaerobic bacteria and protozoa in particular, has a tendency to accumulate in the hypoxic regions and enhance the lethal effect of ionizing radiation for hypoxic tissues.5) The reduction of the nitroimidazole (RNO 2 ) within cells proceeds in successive steps involving enzyme-mediated electron transfer via the free radical anion (RNO

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The Radiopharmaceutical Chemistry of Gallium(III) and Indium(III) for SPECT Imaging

Dilworth

Pascu

2014

The Chemistry of Molecular Imaging

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Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers

Cited by 50 publications

References 33 publications

Development of 68Ga-labeled multivalent nitroimidazole derivatives for hypoxia imaging

Development of 68Ga-labeled multivalent nitroimidazole derivatives for hypoxia imaging

In Vivo Evaluation of a Radiogallium-Labeled Bifunctional Radiopharmaceutical, Ga-DOTA-MN2, for Hypoxic Tumor Imaging

The Radiopharmaceutical Chemistry of Gallium(III) and Indium(III) for SPECT Imaging

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