Comparative studies of Cu-64-ATSM and C-11-Acetate in an acute myocardial infarction model: ex vivo imaging of hypoxia in rats

Fujibayashi, Yasuhisa; Cutler, Cathy S.; Anderson, Carolyn J.; McCarthy, Deborah W.; Jones, Lynne A.; Sharp, Terry L.; Yonekura, Yoshiharu; Welch, Michael J.

doi:10.1016/s0969-8051(98)00049-3

Cited by 101 publications

(76 citation statements)

References 16 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: 95%

“…This has been confirmed through studies performed in our laboratory in which frozen tissue sections from R3327-AT Dunning rat prostate tumor-bearing animals, co-injected with pimonidazole and 18 F-FMISO, showed a high correlation between the fluorescence intensity of the anti-pimonidazole antibody with the digital autoradiographic intensity of the 18 F hypoxia tracer. Other investigators have identified different hypoxia tracers such as 64 Cu-ATSM (63)(64)(65)(66). Groups using each of these hypoxia radiotracers have discussed their potential for RT dose painting as proposed by Ling et al (40).…”

Section: Discussionmentioning

confidence: 99%

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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

208

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: 95%

Section: Discussionmentioning

confidence: 99%

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

208

157

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“…with blood pool correction performed from perfusion image. (Reproduced with permission from Fujibayashi et al [98]). Autoradiographic images showing tracer accumulation in heart sections from an LAD-occluded rat heart.…”

Section: Discussionmentioning

confidence: 99%

“…Wood et al observed that after 10 min of tracer injection, Cu-ATSM images in rats bearing carcinosarcoma allografts correlated strongly with flow, while after 60 min, this correlation was lost, revealing a hypoxia-dependent biodistribution [97]. Similarly, Fujibayashi et al showed that regions of acute myocardial ischemia exhibited sub-regions lacking uptake of both 64 Cu-ATSM (10 min post-injection) and 11 C-acetate (1 min post-injection) surrounded by regions of high Cu-ATSM uptake in the hypoxic border zone [98], delivery of both tracers presumably being limited by flow. Conversely, the in vivo pharmacokinetic data obtained by Lewis et al showed no relationship between flow and tracer uptake [99].…”

Section: What Is the Effect Of Perfusion?mentioning

confidence: 95%

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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“…A copper complex of diacetyl-bis(N 4 -methylthiosemicarbazone) (copper-ATSM) was developed as a tracer of hypoxia-selective uptake in the ischemic myocardium (9)(10)(11). Further investigations revealed that copper-ATSM can rapidly (,1 h) delineate hypoxic tumor tissue hypoxia at high contrast in vitro or in vivo (12,13).…”

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confidence: 99%

Pathophysiologic Correlation Between ⁶²Cu-ATSM and ¹⁸F-FDG in Lung Cancer

Lohith¹,

Kudo²,

Demura³

et al. 2009

J Nucl Med

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The purpose of this study was to delineate the differences in intratumoral uptake and tracer distribution of 62 Cu-diacetylbis(N 4 -methylthiosemicarbazone) ( 62 Cu-ATSM), a well-known hypoxic imaging tracer, and 18 F-FDG in patients with lung cancer of pathohistologically different types. Methods: Eight patients with squamous cell carcinoma (SCC) and 5 with adenocarcinoma underwent 62 Cu-ATSM and 18 F-FDG PET within a 1-wk interval. For 62 Cu-ATSM PET, 10-min static data acquisition was started at 10 min after a 370-to 740-MBq tracer injection. After image reconstruction, 62 Cu-ATSM and 18 F-FDG images were coregistered, and multiple small regions of interest were drawn on tumor lesions of the 2 images to obtain standardized uptake values (SUVs). The regression lines were determined between SUVs for 62 Cu-ATSM and 18 F-FDG in each tumor. The slope values were compared between SCC and adenocarcinoma to observe pathohistologic differences in intratumoral distribution of the tracers. Results: SUVs for 62 Cu-ATSM were lower than those for 18 F-FDG in both SCC and adenocarcinoma. SCC tumors showed high 62 Cu-ATSM and low 18 F-FDG uptakes in the peripheral region of tumors but low 62 Cu-ATSM and high 18 F-FDG uptakes toward the center (spatial mismatching). The relationship of SUVs for the 2 tracers was negatively correlated with a mean regression slope of 20.07 6 0.05. On the other hand, adenocarcinoma tumors had a spatially similar distribution of 62 Cu-ATSM and 18 F-FDG, with positive regression slopes averaging 0.24 6 0.13. The regression slopes for 62 Cu-ATSM and 18 F-FDG differed significantly between SCC and adenocarcinoma (P , 0.001). Conclusion: The intratumoral distribution patterns of 62 Cu-ATSM and 18 F-FDG were different between SCC and adenocarcinoma in lung cancers, indicating that intratumoral regions of high glucose metabolism and hypoxia could differ with the pathohistologic type of lung cancer. The identification of regional biologic characteristics in tumors such as hypoxia, energy metabolism, and proliferation could play a significant role in the clinical diagnosis and therapy planning for non-small cell lung cancer patients.

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Comparative studies of Cu-64-ATSM and C-11-Acetate in an acute myocardial infarction model: ex vivo imaging of hypoxia in rats

Cited by 101 publications

References 16 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

PET imaging of cardiac hypoxia: Opportunities and challenges

Pathophysiologic Correlation Between ⁶²Cu-ATSM and ¹⁸F-FDG in Lung Cancer

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Comparative studies of Cu-64-ATSM and C-11-Acetate in an acute myocardial infarction model: ex vivo imaging of hypoxia in rats

Cited by 101 publications

References 16 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

PET imaging of cardiac hypoxia: Opportunities and challenges

Pathophysiologic Correlation Between 62Cu-ATSM and 18F-FDG in Lung Cancer

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Product

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Pathophysiologic Correlation Between ⁶²Cu-ATSM and ¹⁸F-FDG in Lung Cancer