Cell line-dependent differences in uptake and retention of the hypoxia-selective nuclear imaging agent Cu-ATSM

Burgman, Paul; O’Donoghue, Joseph A.; Lewis, Jason S.; Welch, Michael J.; Humm, John L.; Ling, C. Clifton

doi:10.1016/j.nucmedbio.2005.05.003

Cited by 93 publications

(93 citation statements)

References 31 publications

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“…Groups using each of these hypoxia radiotracers have discussed their potential for RT dose painting as proposed by Ling et al (40). Our clinical study focused on the use of 18 F-FMISO because our in vitro (67) and in vivo (17) analyses of 64 Cu-ATSM and 18 F-FMISO demonstrated unresolved tumor cell line uptake kinetic dependence for the 64 Cu-ATSM tracer.…”

Section: Discussionmentioning

confidence: 97%

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

Lee

Mechalakos

Nehmeh

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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157

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Purpose-Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV h ) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV h increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ( 18 F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients.Methods and Materials-18 F-FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and 18 F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated 18 F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate 18 F-FMISO PET/CT-guided IMRT plans.Results-The heterogeneous distribution of 18 F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing 18 F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV h and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV h for 2 patients and were successful in 1, with normal tissue sparing. Conclusion-It was feasible to dose escalate the GTV h to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients.

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Section: Discussionmentioning

confidence: 97%

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

Lee

Mechalakos

Nehmeh

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

Self Cite

210

157

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“…The retention mechanism is not entirely understood but the fast tissue distribution of Cu-ATSM is advantageous. However, several studies have shown that the hypoxia-specificity of Cu-ATSM is tumor cell line dependent in vitro [20,21] as well as in vivo [22Á24] which severely limits its possible role as a universal PET hypoxia imaging agent. As pointed out earlier the tracer ratio between hypoxic and non-hypoxic tumor entities is expected to increase over time as it allows for binding of more tracer and, equally important, clearance of unbound image-contaminating tracer.…”

Section: Discussionmentioning

confidence: 99%

Resolution in PET hypoxia imaging: Voxel size matters

2008

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“…It is not yet known whether this is also true in cardiac tissue, or whether the fate of radiocopper is ischemia-or hypoxia-dependent, or varies between different BTSC complexes. Burgman et al have suggested a further selectivity mechanism, that of transporter-mediated efflux of radiocopper from the cell, where the cell-dependent differences that they observe in radiocopper retention may be governed by differences in expression of the copper exporters ATP7A and ATP7B [107]. This has not yet been investigated further.…”

Section: What Is Fate Of the Radiocopper?mentioning

confidence: 99%

PET imaging of cardiac hypoxia: Opportunities and challenges

Handley¹,

Medina²,

Nagel

et al. 2011

Journal of Molecular and Cellular Cardiology

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Myocardial hypoxia is a major factor in the pathology of cardiac ischemia and myocardial infarction. Hypoxia also occurs in microvascular disease and cardiac hypertrophy, and is thought to be a prime determinant of the progression to heart failure, as well as the driving force for compensatory angiogenesis. The non-invasive delineation and quantification of hypoxia in cardiac tissue therefore has the potential to be an invaluable experimental, diagnostic and prognostic biomarker for applications in cardiology. However, at this time there are no validated methodologies sufficiently sensitive or reliable for clinical use. PET imaging provides real-time spatial information on the biodistribution of injected radiolabeled tracer molecules. Its inherent high sensitivity allows quantitative imaging of these tracers, even when injected at subpharmacological (≥pM) concentrations, allowing the non-invasive investigation of biological systems without perturbing them. PET is therefore an attractive approach for the delineation and quantification of cardiac hypoxia and ischemia. In this review we discuss the key concepts which must be considered when imaging hypoxia in the heart. We summarize the PET tracers which are currently available, and we look forward to the next generation of hypoxia-specific PET imaging agents currently being developed. We describe their potential advantages and shortcomings compared to existing imaging approaches, and what is needed in terms of validation and characterization before these agents can be exploited clinically.

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Cell line-dependent differences in uptake and retention of the hypoxia-selective nuclear imaging agent Cu-ATSM

Cited by 93 publications

References 31 publications

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

Resolution in PET hypoxia imaging: Voxel size matters

PET imaging of cardiac hypoxia: Opportunities and challenges

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