FDG PET/CT in patients with HIV.

OBJECTIVE: This article will discuss the (18)F-FDG normal variant uptake and the role of FDG PET/CT in malignancies in HIV-infected patients, CNS manifestations of HIV, assessing fever of unknown origin in HIV patients, assessing response to highly active antiretroviral therapy and assessing complications. CONCLUSION: FDG PET/CT is a valuable imaging study in the management of HIV-infected patients.

Use of 18F-FDG PET/CT as a predictive biomarker of outcome in patients with head-and-neck non-squamous cell carcinoma.

OBJECTIVE: The purpose of this article is to establish whether pretreatment (18)F-FDG uptake predicts disease-free survival (DFS) and overall survival in patients with head-and-neck non-squamous cell carcinoma (SCC). MATERIALS AND METHODS: Eighteen patients (six women and 12 men; mean [± SD] age at diagnosis, 57.89 ± 13.54 years) with head-and-neck non-SCC were included. Tumor FDG uptake was measured by the maximum standardized uptake value (SUV(max)) and was corrected for background liver FDG uptake to derive the corrected SUV(max). Receiver operating characteristic analyses were used to predict the optimal corrected SUV(max) cutoffs for respective outcomes of DFS (i.e., absence of recurrence) and death. RESULTS: The mean corrected SUV(max) of the 18 head-and-neck tumors was 5.63 ± 3.94 (range, 1.14-14.29). The optimal corrected SUV(max) cutoff for predicting DFS and overall survival was 5.79. DFS and overall survival were significantly higher among patients with corrected SUV(max) < 6 than among patients with corrected SUV(max) ≥ 6. The mean DFS for patients with corrected SUV(max) < 6 was 25.7 ± 11.14 months, and the mean DFS for patients with corrected SUV(max) ≥ 6 was 7.88 ± 7.1 months (p < 0.018). Among patients with corrected SUV(max) < 6, none died, and the mean length of follow-up for this group was 35.2 ± 9.96 months. All of the patients who died had corrected SUV(max) ≥ 6, and the overall survival for this group was 13.28 ± 12.89 months (p < 0.001). CONCLUSION: FDG uptake, as measured by corrected SUV(max), may be a predictive imaging biomarker for DFS and overall survival in patients with head-and-neck non-SCC.

Squamous cell carcinoma of the palatine tonsils: FDG standardized uptake value ratio as a biomarker to differentiate tonsillar carcinoma from physiologic uptake.

PURPOSE: To quantify fluorine 18 ((18)F) fluorodeoxyglucose (FDG) uptake in the palatine tonsils to identify a sensitive and specific metric for distinguishing physiologic asymmetric uptake from squamous cell carcinoma (SCC). MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by institutional review board. Informed consent requirements were waived. Twenty-six patients (seven female, 19 male; mean age, 53.46 years + or - 10.45 [standard deviation]) with tonsillar SCC were included. Twenty-six patients (seven female, 19 male; mean age, 61.77 years + or - 10.12) with head and neck carcinomas not involving the tonsils were included as control subjects. Tonsil standardized uptake values (SUVs) were measured bilaterally in each group. Independent-samples t test was used to compare mean SUVs, and Pearson correlation was used to evaluate association of FDG uptake between tonsils within control subjects. RESULTS: The mean maximum SUV (SUV(max)) of tonsil tumors was 9.36 + or - 4.54, which was significantly higher than that of contralateral cancer-free tonsils (2.54 + or - 0.88; P < .0001) and tonsils in control subjects (2.98 + or - 1.08; P < .0001). In patients with tonsillar cancer, the mean difference in SUV(max) between tonsils was 10.43 + or - 7.07, which was significantly greater than that in control subjects (0.62 + or - 0.54; P < .0001). The mean SUV(max) ratio between tonsils in patients with carcinoma was 3.79 + or - 1.69, which was threefold higher than in control subjects (1.18 + or - 0.13; P < .0001). For receiver operating characteristic analysis using SUV(max) ratio to differentiate benign uptake from SCC, the area under the curve was 1.00 (95% confidence interval: 1.00, 1.00). A cutoff ratio of 1.48 had 100% sensitivity and specificity. CONCLUSION: The SUV(max) ratio represents an accurate imaging biomarker for differentiating tonsillar SCC from physiologic (18)F-FDG uptake.

Raising gestational choline intake alters gene expression in DMBA-evoked mammary tumors and prolongs survival.

Choline is an essential nutrient that serves as a donor of metabolic methyl groups used during gestation to establish the epigenetic DNA methylation patterns that modulate tissue-specific gene expression. Because the mammary gland begins its development prenatally, we hypothesized that choline availability in utero may affect the gland's susceptibility to cancer. During gestational days 11-17, pregnant rats were fed a control, choline-supplemented, or choline-deficient diet (8, 36, and 0 mmol/kg of choline, respectively). On postnatal day 65, the female offspring received 25 mg/kg of a carcinogen 7,12-dimethylbenz[alpha]anthracene. Approximately 70% of the rats developed mammary adenocarcinomas; prenatal diet did not affect tumor latency, incidence, size, and multiplicity. Tumor growth rate was inversely related to choline content in the prenatal diet, resulting in 50% longer survival until euthanasia, determined by tumor size, of the prenatally choline-supplemented rats compared with the prenatally choline-deficient rats. This was accompanied by distinct expression patterns of approximately 70 genes in tumors derived from the three dietary groups. Tumors from the prenatally choline-supplemented rats overexpressed genes that confer favorable prognosis in human cancers (Klf6, Klf9, Nid2, Ntn4, Per1, and Txnip) and underexpressed those associated with aggressive disease (Bcar3, Cldn12, Csf1, Jag1, Lgals3, Lypd3, Nme1, Ptges2, Ptgs1, and Smarcb1). DNA methylation within the tumor suppressor gene, stratifin (Sfn, 14-3-3sigma), was proportional to the prenatal choline supply and correlated inversely with the expression of its mRNA and protein in tumors, suggesting that an epigenetic mechanism may underlie the altered molecular phenotype and tumor growth. Our results suggest a role for adequate maternal choline nutrition during pregnancy in prevention/alleviation of breast cancer in daughters.

Gestational choline supply regulates methylation of histone H3, expression of histone methyltransferases G9a (Kmt1c) and Suv39h1 (Kmt1a), and DNA methylation of their genes in rat fetal liver and brain.

Choline is an essential nutrient that, via its metabolite betaine, serves as a donor of methyl groups used in fetal development to establish the epigenetic DNA and histone methylation patterns. Supplementation with choline during embryonic days (E) 11-17 in rats improves memory performance in adulthood and protects against age-related memory decline, whereas choline deficiency impairs certain cognitive functions. We previously reported that global and gene-specific DNA methylation increased in choline-deficient fetal brain and liver, and these changes in DNA methylation correlated with an apparently compensatory up-regulation of the expression of DNA methyltransferase Dnmt1. In the current study, pregnant rats were fed a diet containing varying amounts of choline (mmol/kg: 0 (deficient), 8 (control), or 36 (supplemented)) during E11-17, and indices of histone methylation were assessed in liver and frontal cortex on E17. The mRNA and protein expression of histone methyltransferases G9a and Suv39h1 were directly related to the availability of choline. DNA methylation of the G9a and Suv39h1 genes was up-regulated by choline deficiency, suggesting that the expression of these enzymes is under negative control by methylation of their genes. The levels of H3K9Me2 and H3K27Me3, tags of transcriptionally repressed chromatin, were up-regulated by choline supplementation, whereas the levels of H3K4Me2, associated with active promoters, were highest in choline-deficient rats. These data show that maternal choline supply during pregnancy modifies fetal histone and DNA methylation, suggesting that a concerted epigenomic mechanism contributes to the long term developmental effects of varied choline intake in utero.

Gestational choline deficiency causes global and Igf2 gene DNA hypermethylation by up-regulation of Dnmt1 expression.

During gestation there is a high demand for the essential nutrient choline. Adult rats supplemented with choline during embryonic days (E) 11-17 have improved memory performance and do not exhibit age-related memory decline, whereas prenatally choline-deficient animals have memory deficits. Choline, via betaine, provides methyl groups for the production of S-adenosylmethionine, a substrate of DNA methyltransferases (DNMTs). We describe an apparently adaptive epigenomic response to varied gestational choline supply in rat fetal liver and brain. S-Adenosylmethionine levels increased in both organs of E17 fetuses whose mothers consumed a choline-supplemented diet. Surprisingly, global DNA methylation increased in choline-deficient animals, and this was accompanied by overexpression of Dnmt1 mRNA. Previous studies showed that the prenatal choline supply affects the expression of multiple genes, including insulin-like growth factor 2 (Igf2), whose expression is regulated in a DNA methylation-dependent manner. The differentially methylated region 2 of Igf2 was hypermethylated in the liver of E17 choline-deficient fetuses, and this as well as Igf2 mRNA levels correlated with the expression of Dnmt1 and with hypomethylation of a regulatory CpG within the Dnmt1 locus. Moreover, mRNA expression of brain and liver Dnmt3a and methyl CpG-binding domain 2 (Mbd2) protein as well as cerebral Dnmt3l was inversely correlated to the intake of choline. Thus, choline deficiency modulates fetal DNA methylation machinery in a complex fashion that includes hypomethylation of the regulatory CpGs within the Dnmt1 gene, leading to its overexpression and the resultant increased global and gene-specific (e.g. Igf2) DNA methylation. These epigenomic responses to gestational choline supply may initiate the long term developmental changes observed in rats exposed to varied choline intake in utero.