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Correlation of Tumor Hypoxia Metrics Derived from ¹⁸F-Fluoromisonidazole Positron Emission Tomography and Pimonidazole Fluorescence Images of Optically Cleared Brain Tissue.

ABSTRACT: ¹⁸F-fluoromisonidazole (FMISO) positron emission tomography (PET) is a widely used noninvasive imaging modality for assessing hypoxia. We describe the first spatial comparison of FMISO PET with an ex vivo reference standard for hypoxia across whole tumor volumes. Eighteen rats were orthotopically implanted with C6 or 9L brain tumors and made to undergo FMISO PET scanning. Whole brains were excised, sliced into 1-mm-thick sections, optically cleared, and fluorescently imaged for pimonidazole using an in vivo imaging system. FMISO maximum tumor uptake, maximum tumor-to-cerebellar uptake (TCmax), and hypoxic fraction (extracted 110?minutes after FMISO injection) were correlated with analogous metrics derived from pimonidazole fluorescence images. FMISO SUVmax was not significantly different between C6 and 9L brain tumors (P?=?.70), whereas FMISO TCmax and hypoxic fraction were significantly greater for C6 tumors (P?<?.01). FMISO TCmax was significantly correlated with the maximum tumor pimonidazole intensity (? = 0.76, P?<?.01), whereas FMISO SUVmax was not. FMISO tumor hypoxic fraction was significantly correlated with the pimonidazole-derived hypoxic fraction (? = 0.78, P?<?.01). Given that FMISO TCmax and tumor hypoxic fraction had strong correlations with the pimonidazole reference standard, these metrics may offer more reliable measures of tumor hypoxia than conventional PET uptake metrics (SUVmax). The voxel-wise correlation between FMISO uptake and pimonidazole intensity for a given tumor was strongly dependent on the tumor's TCmax (? = 0.81, P?<?.01) and hypoxic fraction (? = 0.85, P?<?.01), indicating PET measurements within individual voxels showed greater correlation with pimonidazole reference standard in tumors with greater hypoxia.

SUBMITTER: Scarpelli ML

PROVIDER: S-EPMC7744194 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Correlation of Tumor Hypoxia Metrics Derived from <sup>18</sup>F-Fluoromisonidazole Positron Emission Tomography and Pimonidazole Fluorescence Images of Optically Cleared Brain Tissue.

Scarpelli Matthew L ML Healey Debbie R DR Fuentes Alberto A Kodibagkar Vikram D VD Quarles C Chad CC

Tomography (Ann Arbor, Mich.) 20201201 4

<sup>18</sup>F-fluoromisonidazole (FMISO) positron emission tomography (PET) is a widely used noninvasive imaging modality for assessing hypoxia. We describe the first spatial comparison of FMISO PET with an ex vivo reference standard for hypoxia across whole tumor volumes. Eighteen rats were orthotopically implanted with C6 or 9L brain tumors and made to undergo FMISO PET scanning. Whole brains were excised, sliced into 1-mm-thick sections, optically cleared, and fluorescently imaged for pimoni ...[more]

PMID: 33364428

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Project description:BackgroundMicrocalcifications in atherosclerotic plaques are destabilizing, predict adverse cardiovascular events, and are associated with increased morbidity and mortality.18F-fluoride positron emission tomography (PET)/computed tomography (CT) imaging has demonstrated promise as a useful clinical diagnostic tool in identifying high-risk plaques; however, there is confusion as to the underlying mechanism of signal amplification seen in PET-positive, CT-negative image regions. This study tested the hypothesis that 18F-fluoride PET/CT can identify early microcalcifications.Methods18F-fluoride signal amplification derived from microcalcifications was validated against near-infrared fluorescence molecular imaging and histology using an in vitro 3-dimensional hydrogel collagen platform, ex vivo human specimens, and a mouse model of atherosclerosis.ResultsMicrocalcification size correlated inversely with collagen concentration. The 18F-fluoride ligand bound to microcalcifications formed by calcifying vascular smooth muscle cell derived extracellular vesicles in the in vitro 3-dimensional collagen system and exhibited an increasing signal with an increase in collagen concentration (0.25 mg/mL collagen -33.8×102±12.4×102 counts per minute; 0.5 mg/mL collagen -67.7×102±37.4×102 counts per minute; P=0.0014), suggesting amplification of the PET signal by smaller microcalcifications. We further incubated human atherosclerotic endarterectomy specimens with clinically relevant concentrations of 18F-fluoride. The 18F-fluoride ligand labeled microcalcifications in PET-positive, CT-negative regions of explanted human specimens as evidenced by 18F-fluoride PET/CT imaging, near-infrared fluorescence, and histological analysis. Additionally, the 18F-fluoride ligand identified micro and macrocalcifications in atherosclerotic aortas obtained from low-density lipoprotein receptor-deficient mice.ConclusionsOur results suggest that 18F-fluoride PET signal in PET-positive, CT-negative regions of human atherosclerotic plaques is the result of developing microcalcifications, and high surface area in regions of small microcalcifications may amplify PET signal.

Dataset Information

Correlation of Tumor Hypoxia Metrics Derived from ¹⁸F-Fluoromisonidazole Positron Emission Tomography and Pimonidazole Fluorescence Images of Optically Cleared Brain Tissue.

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Correlation of Tumor Hypoxia Metrics Derived from <sup>18</sup>F-Fluoromisonidazole Positron Emission Tomography and Pimonidazole Fluorescence Images of Optically Cleared Brain Tissue.

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Dataset Information

Correlation of Tumor Hypoxia Metrics Derived from 18F-Fluoromisonidazole Positron Emission Tomography and Pimonidazole Fluorescence Images of Optically Cleared Brain Tissue.

Publications

Correlation of Tumor Hypoxia Metrics Derived from <sup>18</sup>F-Fluoromisonidazole Positron Emission Tomography and Pimonidazole Fluorescence Images of Optically Cleared Brain Tissue.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Correlation of Tumor Hypoxia Metrics Derived from ¹⁸F-Fluoromisonidazole Positron Emission Tomography and Pimonidazole Fluorescence Images of Optically Cleared Brain Tissue.