Dataset Information

A reactivity-based [18F]FDG probe for in vivo formaldehyde imaging using positron emission tomography.

ABSTRACT: Formaldehyde (FA) is a reactive carbonyl species (RCS) that plays a broad spectrum of roles in epigenetics, toxicology, and progression of diseases ranging from cancer to diabetes to neurodegeneration, motivating the development of translatable technologies for FA imaging. Here we report formaldehyde-caged-[18F]fluorodeoxyglucose-1 ([18F]FAC-FDG-1), an aza-Cope-based reactivity probe for in vivo FA imaging using positron emission tomography (PET). [18F]FAC-FDG-1 reacts selectively with FA over potentially competing analytes to generate [18F]FDG, allowing its FA-dependent uptake and retention in cell culture as well as in animal models. The relative uptake of [18F]FAC-FDG-1 was evaluated using FA-treated PC3 prostate cancer and U87-MG glioblastoma cells demonstrating a dose-dependent response to exogenously added FA. Moreover, [18F]FAC-FDG-1 is capable of FA detection in vivo using a PC3 tumor xenograft model. In addition to providing a unique tool for monitoring FA in living animals, these data establish a general approach for translatable detection of FA and other reactive biological analytes in vivo by exploiting the widely-available clinical [18F]FDG tracer as a masked aldehyde that can be caged by analyte-responsive triggers.

SUBMITTER: Liu W

PROVIDER: S-EPMC6021783 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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A reactivity-based [18F]FDG probe for in vivo formaldehyde imaging using positron emission tomography.

Liu Wei W Truillet Charles C Flavell Robert R RR Brewer Thomas F TF Evans Michael J MJ Wilson David M DM Chang Christopher J CJ

Chemical science 20160525 8

Formaldehyde (FA) is a reactive carbonyl species (RCS) that plays a broad spectrum of roles in epigenetics, toxicology, and progression of diseases ranging from cancer to diabetes to neurodegeneration, motivating the development of translatable technologies for FA imaging. Here we report formaldehyde-caged-[18F]fluorodeoxyglucose-1 ([18F]FAC-FDG-1), an aza-Cope-based reactivity probe for in vivo FA imaging using positron emission tomography (PET). [18F]FAC ...[more]

PMID: 30034690

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Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Project description:BackgroundPheochromocytomas and paragangliomas (PPGLs) are rare tumors of the adrenal medulla and extra-adrenal sympathetic chromaffin tissues; their anatomical and functional imaging are critical to guiding treatment decisions. This study aimed to compare the sensitivity and specificity of (18)F-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG PET/CT) for tumor localization and staging of PPGLs with that of conventional imaging by [(123)I]-metaiodobenzylguanidine single photon emission CT ((123)I-MIBG SPECT), CT, and magnetic resonance imaging (MRI).MethodsA total of 216 patients (106 men, 110 women, aged 45.2 ± 14.9 years) with suspected PPGL underwent CT or MRI, (18)F-FDG PET/CT, and (123)I-MIBG SPECT/CT. Sensitivity and specificity were measured as endpoints and compared by the McNemar test, using two-sided P values only.ResultsSixty (28%) of patients had nonmetastatic PPGL, 95 (44%) had metastatic PPGL, and 61 (28%) were PPGL negative. For nonmetastatic tumors, the sensitivity of (18)F-FDG was similar to that of (123)I-MIBG but less than that of CT/MRI (sensitivity of (18)F-FDG = 76.8%; of (123)I-MIBG = 75.0%; of CT/MRI = 95.7%; (18)F-FDG vs (123)I-MIBG: difference = 1.8%, 95% confidence interval [CI] = -14.8% to 14.8%, P = .210; (18)F-FDG vs CT/MRI: difference = 18.9%, 95% CI = 9.4% to 28.3%, P < .001). The specificity was 90.2% for (18)F-FDG, 91.8% for (123)I-MIBG, and 90.2% for CT/MRI. (18)F-FDG uptake was higher in succinate dehydrogenase complex- and von Hippel-Lindau syndrome-related tumors than in multiple endocrine neoplasia type 2 (MEN2) related tumors. For metastases, sensitivity was greater for (18)F-FDG and CT/MRI than for (123)I-MIBG (sensitivity of (18)F-FDG = 82.5%; of (123)I-MIBG = 50.0%; of CT/MRI = 74.4%; (18)F-FDG vs (123)I-MIBG: difference = 32.5%, 95% CI = 22.3% to 42.5%, P < .001; CT/MRI vs (123)I-MIBG: difference = 24.4%, 95% CI = 11.3% to 31.6%, P < .001). For bone metastases, (18)F-FDG was more sensitive than CT/MRI (sensitivity of (18)F-FDG = 93.7%; of CT/MRI = 76.7%; difference = 17.0%, 95% CI = 4.9% to 28.5%, P = .013).ConclusionsCompared with (123)I-MIBG SPECT and CT/MRI, both considered gold standards for PPGL imaging, metastases were better detected by (18)F-FDG PET. (18)F-FDG PET provides a high specificity in patients with a biochemically established diagnosis of PPGL.

Dataset Information

A reactivity-based [18F]FDG probe for in vivo formaldehyde imaging using positron emission tomography.

Publications

A reactivity-based [<sup>18</sup>F]FDG probe for <i>in vivo</i> formaldehyde imaging using positron emission tomography.

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