The Potential Role of Positron Emission Tomography in Investigation of Microenvironment

Laubenbacher, C.; Schwaiger, Markus

doi:10.1007/978-3-642-58813-6_15

Cited by 4 publications

(4 citation statements)

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“…Considering the molecular weight of Fmiso and the distances the molecules have to travel from the vessel to the hypoxic cell (Jain 1987), the diffusion time will be high compared to other tracers with active transport mechanisms and shorter diffusion distances (such as e.g. FDG (Laubenbacher and Schwaiger et al 2000)). The time the marker needs to reach the hypoxic tissue area far from the blood vessel will be in the order of 100-1000 s, as motivated in the following.…”

Section: Kinetic Modelmentioning

confidence: 99%

“…At low oxygen levels, the compound is reduced and binds, when reduced by a second electron, covalently to intracellular macromolecules. In the presence of oxygen, the favoured reaction is the re-oxygenation to the less reactive parent compound which is freely diffusible and clears from tissue (Laubenbacher and Schwaiger 2000). Koh et al (1992) and Rasey et al (1996) developed a strategy for the identification and quantification of hypoxic tumour areas on the basis of Fmiso PET images.…”

Section: Introductionmentioning

confidence: 99%

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A kinetic model for dynamic [¹⁸F]-Fmiso PET data to analyse tumour hypoxia

Thorwarth¹,

Eschmann

Paulsen³

et al. 2005

Phys. Med. Biol.

159

142

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A method is presented to identify and quantify hypoxia in human head-and-neck tumours based on dynamic [18F]-Fmiso PET patient data, using a model for the tracer transport. A compartmental model was developed, inspired by recent immunohistochemical investigations with the tracer pimonidazole. In order to take the trapping of the tracer and the diffusion in interstitial space into account, the kinetic model consists of two compartments and a specific input function. This voxel-based data analysis allows us to decompose the time-activity curves (TACs) into their perfusion, diffusion and hypoxia-induced retention components. This characterization ranges from well perfused tumours over diffusion limited hypoxia to strong hypoxia and necrosis. The overall shape of the TAC and the model parameters may point at the structural architecture of the tissue sample. The model addresses the two main problems associated with hypoxia imaging with PET. Firstly, the hypoxic areas are spatially separated from well perfused vessels, causing long diffusion times of the tracer. Secondly, tracer uptake occurs only in viable hypoxic cells, which constitute only a small subpopulation in the presence of necrosis. The resulting parameters such as the concentration of hypoxic cells and the perfusion are displayed in parameter plots ('hypoxia map'). Quantification of hypoxia performed with the presented kinetic model is more reliable than a criterion based on static standardized uptake values (SUV) at an early timepoint, because severely hypoxic/necrotic tissues show low uptake and are thus overlooked by SUV threshold identification. The derived independent measures for perfusion and hypoxia may provide a basis for individually adapted treatment planning.

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Section: Kinetic Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A kinetic model for dynamic [¹⁸F]-Fmiso PET data to analyse tumour hypoxia

Thorwarth¹,

Eschmann

Paulsen³

et al. 2005

Phys. Med. Biol.

159

142

View full text Add to dashboard Cite

show abstract

“…(53) were the first to detect tumor hypoxia with nitroimidazole compounds and molecular imaging. The widespread use of PET for imaging hypoxia is made possible through the use of exogenous markers, hypoxia-specific agents that are reduced and covalently bind to intracellular macromolecules in the tumor in the absence of oxygen (54). Figure 2 shows representative clinical images of PET radiotracers for tumor hypoxia.…”

Section: Pet Imaging To Identify Tumor Hypoxia: Current Status Of Petmentioning

confidence: 99%

Molecular Imaging of Tumor Hypoxia with Positron Emission Tomography

Kelada

Carlson

2014

Radiation Research

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The problem of tumor hypoxia has been recognized and studied by the oncology community for over 60 years. From radiation and chemotherapy resistance to the increased risk of metastasis, the low oxygen concentrations in tumors have caused patients with many types of tumors to respond poorly to conventional cancer therapies. It is clear that patients with high levels of tumor hypoxia have a poorer overall treatment response and that the magnitude of hypoxia is an important prognostic factor. As a result, the development of methods to measure tumor hypoxia using invasive and non-invasive techniques has become desirable to the clinical oncology community. A variety of imaging modalities have been established to visualize hypoxia in vivo. Positron Emission Tomography (PET) imaging, in particular, has played a key role for imaging tumor hypoxia because of the development of hypoxia-specific radiolabelled agents. Consequently, this technique is increasingly used in the clinic for a wide variety of cancer types. Following a broad overview of the complexity of tumor hypoxia and measurement techniques to date, this review will focus specifically on the accuracy and reproducibility of PET imaging to quantify tumor hypoxia. Despite numerous advances in the field of PET imaging for hypoxia, we continue to search for the ideal hypoxia tracer to both qualitatively and quantitatively define the tumor hypoxic volume in a clinical setting to optimize treatments and predict response in cancer patients.

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“…[ 18 F]Fluoromisonidazole ([ 18 F]FMISO) PET [8] is considered one of the more promising hypoxia quantification methods because the tracer selectively binds in hypoxic cells [9-12]. [ 18 F]FMISO is reduced by nitroreductase enzymes and covalently bound to intracellular macromolecules in the absence of oxygen, causing accumulation of F-18 radioactivity in hypoxic cells [13]. Others [9-10] first demonstrated [ 18 F]FMISO could detect hypoxia in human tumors [11] and showed the biomarker was representative of intracellular p O 2 [14].…”

Section: Introductionmentioning

confidence: 99%

Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [18F]Fluoromisonidazole ([18F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements

et al. 2017

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Purpose The purpose of this study is to use dynamic [18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) to compare estimates of tumor hypoxic fractions (HFs) derived by tracer kinetic modeling, tissue-to-blood ratios (TBR), and independent oxygen (pO2) measurements. Procedures BALB/c mice with EMT6 subcutaneous tumors were selected for PET imaging and invasive pO2 measurements. Data from 120 min dynamic [18F]FMISO scans were fit to 2-compartment irreversible 3 rate constant (K1, k2, k3) and Patlak models (Ki). Tumor HFs were calculated and compared using Ki, k3, TBR, and pO2 values. The clinical impact of each method was evaluated on [18F]FMISO scans for three non-small cell lung cancer (NSCLC) radiotherapy patients. Results HFs defined by TBR (≥1.2, ≥1.3 and ≥1.4) ranged from 2-85% of absolute tumor volume. HFs defined by Ki (>0.004 ml·min·cm-3) and k3 (>0.008 min-1) varied from 9-85%. HF quantification was highly dependent on metric (TBR, k3, or Ki) and threshold. HFs quantified on human [18F]FMISO scans varied from 38-67%, 0-14%, and 0.1-27%, for each patient, respectively, using TBR, k3, and Ki metrics. Conclusions [18F]FMISO PET imaging metric choice and threshold impacts hypoxia quantification reliability. Our results suggest that tracer kinetic modeling has the potential to improve hypoxia quantification clinically as it may provide a stronger correlation with direct pO2 measurements.

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The Potential Role of Positron Emission Tomography in Investigation of Microenvironment

Cited by 4 publications

References 168 publications

A kinetic model for dynamic [¹⁸F]-Fmiso PET data to analyse tumour hypoxia

A kinetic model for dynamic [¹⁸F]-Fmiso PET data to analyse tumour hypoxia

Molecular Imaging of Tumor Hypoxia with Positron Emission Tomography

Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [18F]Fluoromisonidazole ([18F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements

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The Potential Role of Positron Emission Tomography in Investigation of Microenvironment

Cited by 4 publications

References 168 publications

A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia

A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia

Molecular Imaging of Tumor Hypoxia with Positron Emission Tomography

Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [18F]Fluoromisonidazole ([18F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements

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A kinetic model for dynamic [¹⁸F]-Fmiso PET data to analyse tumour hypoxia

A kinetic model for dynamic [¹⁸F]-Fmiso PET data to analyse tumour hypoxia