PET and Planar Imaging of Tumor Hypoxia With Labeled Metronidazole

Ito, Megumi; Yang, David J.; Mawlawi, Osama; Mendez, Richard; Oh, Chang Sok; Azhdarinia, Ali; Greenwell, Allison C.; Yu, Dongfang; Kim, E. Edmund

doi:10.1016/j.acra.2006.01.007

Cited by 23 publications

(16 citation statements)

References 25 publications

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“…Tc-and 68 Ga-labeled thiol-containing chelators derivatized with metronidazole(s) were previously reported to accumulate in the hypoxic regions in the tumor. 23,24) However, T/B or T/M ratios of these compounds were much lower than those of 67 Ga-DOTA-MN2, probably because of their high lipophilicity. 68 Ga is of great interest as a positron emitter for PET because of its radiophysical properties (t 1/2 =68 min; β + =89% and EC= 11%; E β+max =1.899 MeV).…”

Section: /68mentioning

confidence: 96%

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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Section: /68mentioning

confidence: 96%

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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“…They are rapidly re-oxidized and removed from the normal cells, and thus provide good demarcation between hypoxic and normoxia cells within the lesion (Sun 2010). Preliminary reports suggested that tumor imaging using hypoxia markers may be useful in the assessment of response to treatment (Wiedemann et al 2010;Busk et al 2009Busk et al ,2010Lee et al2009a, b;Wang et al 1999Wang et al , 2009aDehdashti et al 2000Dehdashti et al , 2008Takai et al 2007;Reischl et al 2007;Dietz et al 2007;Ito et al 2006;Schwarz et al 2004;Rajendran et al 2002Rajendran et al , 2003Liu et al 1999;Hustinx et al 1999;Casciari et al 1995;Yang et al 1995), which is not yet confirmed by prospective clinical trials.…”

Section: Hypoxia Imagingmentioning

confidence: 94%

Assessment of Response to Therapy

Gholamrezanezhad

Chirindel

Subramaniam

2012

PET-CT and PET-MRI in Oncology

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“…PET/CT and SPECT/CT agents show high specific activities because they are made through a nuclear transformation and use carrier free forms of isotopes. Moreover, PET/CT and SPECT/CT chelator-based agents do not produce detectable pharmacologic effects but provide important information concerning the characterization of varieties diseases, such as vascular angiogenesis [4][5][6], hypoxia [7][8][9], apoptosis [10][11], cellular signaling and transcriptional activity [12][13][14]. PET/CT and SPECT/CT may assist in the determination of optimal therapeutic dosing, differential diagnosis between inflammation/infection and recurrence, sensitive or resistant to treatment response, grading of tumors, and the prediction of treatment response by selecting patient who may or may not respond to therapy.…”

Section: Importance Of Nuclear Molecular Imaging In Oncologymentioning

confidence: 99%

Molecular Imaging Kits for Hexosamine Biosynthetic Pathway in Oncology

Yang

Kong²,

Oka³

et al. 2012

curr med chem

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Noninvasive imaging assessment of tumor cell proliferation could be helpful in the evaluation of tumor growth potential, the degree of malignancy, and could provide an early assessment of treatment response prior to changes in tumor size determined by computed tomography (CT), magnetic resonance imaging (MRI), Positron emission tomography (PET), Single-Photon emission computed tomography (SPECT) or ultrasonography, respectfully. Understanding of tumor proliferative activity, in turn, could aid in the selection of optimal therapy by estimating patient prognosis and selecting the proper management. PET/CT imaging of (18)F-fluoro-2-deoxy-glucose (FDG) is recognized as a technology for diagnosing the presence and extent of several cancer types. Recently, radiolabeled glucosamine analogues were introduced as a promising SPECT agent to complement FDG imaging to increase specificity and improve the accuracy of lesion size in oncology applications. Radiolabeled glucosamine analogues were developed to localize in the nuclear components of cells primarily via the hexosamine biosynthetic pathway whereas glucose localizes in the cytoplasm of cells through the glycolytic/TCA pathway. This paper reviews novel kit-based radiolabeled glucosamine analogues for metabolic imaging of tumor lesions. The novel radiolabeled glucosamine analogues may increase the specificity in oncology applications and can influence patient diagnosis, planning and monitoring of cancer treatment.

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PET and Planar Imaging of Tumor Hypoxia With Labeled Metronidazole

Cited by 23 publications

References 25 publications

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

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

Assessment of Response to Therapy

Molecular Imaging Kits for Hexosamine Biosynthetic Pathway in Oncology

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