Correction: Preclinical Assessment of Carboplatin Treatment Efficacy in Lung Cancer by 18F-ICMT-11-Positron Emission Tomography.
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ABSTRACT:
SUBMITTER: Witney TH
PROVIDER: S-EPMC7347147 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Correction: Preclinical Assessment of Carboplatin Treatment Efficacy in Lung Cancer by 18F-ICMT-11-Positron Emission Tomography.
Witney Timothy H TH Fortt Robin R Aboagye Eric O EO
PloS one 20200709 7
[This corrects the article DOI: 10.1371/journal.pone.0091694.]. ...[more]
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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.
2011-11-01 | GSE21217 | GEO
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2011-11-01 | E-GEOD-21217 | biostudies-arrayexpress
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Project description:BackgroundIn Lewy body diseases (LBDs) Parkinson disease (PD), and dementia with Lewy bodies (DLB), by the time parkinsonism or cognitive dysfunction manifests clinically, substantial neurodegeneration has already occurred. Biomarkers are needed to identify central LBDs in a preclinical phase, when neurorescue strategies might forestall symptomatic disease. This phase may involve catecholamine deficiency in the autonomic nervous system. We analyzed data from the prospective, observational, long-term PDRisk study to assess the predictive value of low versus normal cardiac 18F-dopamine positron emission tomography (PET), an index of myocardial content of the sympathetic neurotransmitter norepinephrine, in at-risk individuals.MethodsParticipants self-reported risk factor information (genetics, olfactory dysfunction, dream enactment behavior, and orthostatic intolerance or hypotension) at a protocol-specific website. Thirty-four with 3 or more confirmed risk factors underwent serial cardiac 18F-dopamine PET at 1.5-year intervals for up to 7.5 years or until PD was diagnosed.ResultsNine participants had low initial myocardial 18F-dopamine-derived radioactivity (<6,000 nCi-kg/cc-mCi) and 25 had normal radioactivity. At 7 years of follow-up, 8 of 9 with low initial radioactivity and 1 of 11 with normal radioactivity were diagnosed with a central LBD (LBD+) (P = 0.0009 by Fisher's exact test). Conversely, all 9 LBD+ participants had low 18F-dopamine-derived radioactivity before or at the time of diagnosis of a central LBD, whereas among 25 participants without a central LBD only 1 (4%) had persistently low radioactivity (P < 0.0001 by Fisher's exact test).ConclusionCardiac 18F-dopamine PET highly efficiently distinguishes at-risk individuals who are diagnosed subsequently with a central LBD from those who are not.Trial registrationClinicaltrialsgov NCT00775853.FundingDivision of Intramural Research, NIH, NINDS.
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Project description:BACKGROUND:Radiation pneumonitis is a common and potentially fatal complication of radiotherapy (RT). Some patients with radiation pneumonitis show increases in uptake of fluorodeoxyglucose (FDG) on positron emission tomography (PET), but others do not. The exact relationship between radiation pneumonitis and 18F-FDG PET findings remains controversial. METHODS:We used an animal model of radiation pneumonitis involving both radiation and simulated bacterial infection in Wistar rats. Treatment groups (10 rats/group) were as follows: control, RT-only, lipopolysaccharide (LPS)-only, and RT+LPS. All rats had micro-PET scans at 7?weeks after RT (or sham). Histologic, immunohistochemical, and biochemical analyses were performed to evaluate potential mechanisms. RESULTS:Irradiated rats had developed radiation pneumonitis at 7?weeks after RT based on pathology and CT scans. Maximum and mean standardized uptake values (SUVmax and SUVmean) at that time were significantly increased in the LPS group (P < 0.001 for both) and the RT+LPS group (P < 0.001 for both) relative to control, but were not different in the RT-only group (P = 0.156 SUVmax and P = 0.304 SUVmean). The combination of RT and LPS increased the expression of the aerobic glycolysis enzyme PKM2 (P < 0.001) and the glucose transporter GLUT1 (P = 0.004) in lung tissues. LPS alone increased the expression of PKM2 (P = 0.018), but RT alone did not affect PKM2 (P = 0.270) or GLUT1 (P = 0.989). CONCLUSIONS:Aseptic radiation pneumonitis could not be accurately assessed by 18F-FDG PET, but was visualized after simulated bacterial infection via LPS. The underlying mechanism of the model of bacterial infection causing increased FDG uptake may be the Warburg effect.
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