Accurate prediction of cancer prognosis before the start of treatment is important since these predictions often affect the choice of treatment. Prognosis is usually based on anatomical staging and other clinical factors. However, the conventional system is not sufficient to accurately and reliably determine prognosis. Metabolic parameters measured by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) have the potential to provide valuable information regarding prognosis and treatment response evaluation in cancer patients. Among these parameters, volume-based PET parameters such as metabolic tumor volume and total lesion glycolysis are especially promising. However, the measurement of these parameters is significantly affected by the imaging methodology and specific image characteristics, and a standard method for these parameters has not been established. This review introduces volume-based PET parameters as potential prognostic indicators, and highlights methodological considerations for measurement, potential implications, and prospects for further studies.

TLG is a significant independent metabolic prognostic factor for overall survival in patients with SCC of the tonsil.

Resveratrol is gaining attention for its anticancer effects and is also recognized for its antioxidant properties and influence on glucose metabolism. Augmented reactive oxygen species (ROS) and high glycolytic flux are common characteristics of malignant cells. We thus evaluated the effect of resveratrol on cancer cell glucose metabolism and investigated the role of ROS in the response. Methods: Cancer cells were measured for cell content and 18 F-FDG uptake. Assays were performed for lactate production; hexokinase activity and intracellular ROS; and immunoblotting for hypoxia-inducible factor-1a (HIF-1a), Akt, mammalian target of rapamycin, and glucose transporter type 1 (Glut-1). Animal studies were performed with small-animal PET imaging of Lewis lung carcinoma tumor-bearing mice. Results: Resveratrol mildly decreased cell content and more pronouncedly suppressed 18 F-FDG uptake in Lewis lung carcinoma, HT-29 colon, and T47D breast cancer cells. Hence, 18 F-FDG uptake normalized to cell content was reduced to less than half of controls by 24-h exposure to resveratrol. This reduction was attributed to reduced glycolytic flux and Glut-1 expression. Resveratrol also decreased intracellular ROS in patterns that closely paralleled 18 F-FDG uptake. Scavenging of ROS with N-acetyl cysteine, but not inhibition of nicotinamide adenine dinucleotide phosphate oxidase, was sufficient to suppress 18 F-FDG uptake. Conversely, ROS inducers effectively reversed the metabolic response of resveratrol. HIF-1a protein was markedly reduced by resveratrol, and inhibiting HIF-1a expression with cycloheximide or specific small interfering RNAs suppressed 18 F-FDG uptake. The proteosomal inhibitor MG132 partly restored HIF-1a level and 18 F-FDG uptake in resveratrol-treated cells. Resveratrol also inhibited Akt activation; in addition, inhibitors and small interfering RNAs against phosphoinositide 3-kinase decreased 18 F-FDG uptake. Finally, small-animal PET results showed resveratrol treatment to suppress tumor 18 F-FDG uptake in vivo. Conclusion: Resveratrol suppresses cancer cell 18 F-FDG uptake and glycolytic metabolism in a manner that depends on the capacity of resveratrol to inhibit intracellular ROS, which downregulates HIF-1a accumulation. Ther e is recently growing interest in natural products as an addition to the repertoire of agents that may be beneficial in our battle against cancer (1). Resveratrol, a natural polyphenol compound found in such fruits as grapes and berries, has particularly gained intense attention for its promising anticancer effects (2). Initially recognized for its ability to inhibit carcinogenesis at multiple stages (3,4), resveratrol has since been found to exert significant antitumor effects including inhibition of growth (5-7), induction of apoptosis (6-8), and suppression of metastatic potential (9,10).Resveratrol is known to reduce energy expenditure in vivo, mimicking the effects of caloric restriction (11). Recently, several in vitro studies have described an inhibitory effect of resveratrol ...

In this study, surface SUV entropy had a significant correlation with HI in SCLC. Regarding other PET parameters and tumors, no significant correlation with genetic parameters existed.

The utility of 18 F-FDG PET/CT in patients with nasal-type natural killer (NK)/T-cell lymphoma has not been established. Therefore, we evaluated the role of 18 F-FDG PET/CT for determining cancer staging by comparing its results to those of conventional staging methods (CSMs) (physical examination, CT with intravenous contrast, biopsies from primary sites, and bone marrow examinations) in patients with nasal-type NK/T-cell lymphoma. Methods: In this study, 52 consecutive patients (34 men, 18 women; mean age, 49.4 y) with newly diagnosed nasal-type NK/T-cell lymphoma were studied. Anatomic regions (n 5 1,300; 16 nodal and 9 extranodal regions per patient) were assessed with an 18 F-FDG PET/CT scan and with CSMs, and each anatomic region was classified as positive or negative for malignancy. Biopsy and clinical follow-up, including additional imaging studies, were used as the gold standard for diagnosis. Results: Of the 59 nodal and 71 extranodal anatomic regions that were truly positive for malignancy, 18 F-FDG PET/CT detected 58 nodal and 69 extranodal. CSMs, however, detected only 44 of the nodal and 61 of the extranodal anatomic regions that were positive for malignancy (nodal comparison of PET/CT vs. CSMs, P , 0.001; extranodal comparison of PET/CT vs. CSMs, P 5 0.008). PET/CT scans exhibited a significantly better sensitivity (97.7% vs. 80.7%, P , 0.001) than CSMs for the detection of malignant lesions. PET/CT findings altered the original staging category for 12 patients (21.2%) and affected treatment planning in 23 cases (44.2%). Conclusion: Our study demonstrated that 18 F-FDG PET/CT scanning is a valuable modality for staging and treatment planning in patients with nasal-type NK/T-cell lymphoma.

mg administered during two or three annual cycles (12 mg or 24 mg, 3 times a week). The shorter time to ITP development observed in our study may be related to the different cumulative dose and to the different schedule of drug administration.It has been previously suggested that ITP secondary to lymphoproliferative disorders could be ascribed to autoreactive non-malignant B-cell clones, favored by the loss of immune tolerance due to T-cell dysfunction and/or inappropriate pathological (auto)antigen presentation by CLL cells [16,17]. During alemtuzumab treatment, immune-dysregulation of T lymphocytes may further favor autoimmunity.In conclusion, while reporting for the first time the association between lowdose alemtuzumab treatment and ITP in a cohort of CLL patients, we would also suggest to maintain a high level of vigilance and to strongly consider routine monitoring for ITP in patients treated with this agent for any pathologic condition. MethodsWe retrospectively analyzed a cohort of 64 patients affected by CLL, diagnosed according to NCIWG-CLL criteria and referred to the Hematology-BMT Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan between 2003 and. Median age of patients was 68 years (range: 40-83 years).Patients had been treated with low-dose Alemtuzumab, defined as a total weekly dose lower than 45 mg and a cumulative dose inferior to 600 mg, administered for up to 18 weeks [18,19,20].The diagnosis of ITP was based on (1) an otherwise unexplained, rapid (<2 weeks) and severe fall (at least half of the initial level and below 100 3 10 9 /L) of the platelet counts; (2) a normal or augmented number of megakaryocytes in the bone marrow; (3) no or limited (not palpable) splenomegaly, and (4) no cytotoxic treatment in the last month except for alemtuzumab. We also evaluated assays for antibodies to specific platelet glycoproteins, even if they are not routinely recommended, as platelet-associated IgG is elevated in both immune and non-immune thrombocytopenia [21]. Conflict of interest: Nothing to report. A.C., G.R., C.V., and F.R. designed the research study; F.M., G.G., G.R., A.G., F.B., and F.G. performed the research; F.M., G.G., A.G., and A.P. analyzed the data; A.C., G.R., F.M., G.G., C.V. wrote the paper. The impact of baseline and interim PET/CT parameters on clinical outcome in patients with diffuse large B cell lymphoma F-FDG PET/CT as a tool for guidance in risk stratification in patients with aggressive non-Hodgkin's lymphoma (NHL). Here, we analyzed the predictive value of various PET/CT parameters in patients with DLBCL. Particularly, we were interested in patients with an IPI score of 1, 2, or 3, whose prognosis are confusing. Between Jul 2008 and Feb 2010, a total of 100 patients (including 57 patients with an IPI score of 1-3) who were treated with R-CHOP for DLBCL, and had assessable PET/CT parameters were analyzed in this study. Absolute value of SUV max , SUV sum (sum of SUV max ) and TLG sum (SUV mean x Volume meta ) from baseline and interim PET/CT, and DS...

We investigated the relation of carotid 18 F-FDG uptake to high-sensitivity C-reactive protein (hsCRP) and Framingham risk score (FRS) in a large cohort of asymptomatic adults. Methods: Carotid artery 18 F-FDG uptake was measured on the PET/CT scans of 1,181 asymptomatic subjects, and maximum target-to-background ratio (M-TBR) and intima-media thickness (IMT) were compared with clinical risk factors and hsCRP. The estimated 10-y risk for general cardiovascular disease was calculated by FRS. Results: FRS increased from 11.5% 6 7.8% to 14.8% 6 10.5% in subjects with an M-TBR $ 1.7, compared with , 1.7, and the odds ratio for an FRS $ 10% was 1.9 (95% confidence interval [CI], 1.4-2.5). Adjusting for age confirmed a significant association of M-TBR and IMT with FRS. Independent determinants of high M-TBR were abdominal fat (b coefficient [B], 1.1040; P , 0.0001), low-density lipoprotein (LDL) (B, 0.0006; P , 0.05), and FRS (B, 0.0025; P , 0.05) for subjects , 50 y and abdominal fat (B, 0.9740; P , 0.0001), age (B, 0.0040; P 5 0.0001), LDL (B, 0.0008; P 5 0.0001), and IMT (B, 0.1097; P , 0.01) for subjects $ 50 y. Although hsCRP also stratified subjects for FRS-based risk, no correlation was found between hsCRP and M-TBR or IMT, suggesting that they may have different inferences. Importantly, in the low-hsCRP (14.2% 6 9.7% vs. 11.3% 6 7.4%) and high-hsCRP groups (18.8% 6 14.3% vs. 13.3% 6 10.2%), FRS was significantly greater for subjects with high M-TBR than for those with low M-TBR. The odds ratio for FRS $ 10% between subjects with high and low M-TBR was 1.20 (95% CI, 0.90-1.60; P 5 0.209) in the low-hsCRP group and 2.95 (95% CI, 1.48-5.86; P 5 0.002) in the high-hsCRP group. Conclusion: High carotid 18 F-FDG uptake in asymptomatic adults is associated with increased clinical risk factors and FRS. Furthermore, it appears to reflect aspects of atherosclerotic inflammation distinct from hsCRP concentration and may offer incremental information regarding cardiovascular risk.

There is rising interest in recruitment of brown adipocytes into white adipose tissue (WAT) as a means to augment energy expenditure for weight reduction. We thus investigated the potential of 18 F-FDG uptake as an imaging biomarker that can monitor the process of WAT browning. Methods: C57BL/6 mice were treated daily with the β3 agonist CL316,243 (5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl] amino]propyl]-1,3-benzodioxole-2,2-dicarboxylic acid disodium salt), whereas controls received saline. 18 F-FDG small-animal PET/CT was serially performed at 1 h after CL316,243 injection. After sacrifice, interscapular brown adipose tissue (BAT) and WAT depots were extracted, weighed, and measured for 18 F-FDG uptake. Tissues underwent immunostaining, and UCP1 content was quantified by Western blotting. Results: PET/CT showed low 18 F-FDG uptake in both BAT and inguinal WAT at baseline. BAT uptake was substantially increased by a single stimulation with CL316,243. Uptake in inguinal WAT was only modestly elevated by the first stimulation uptake but gradually increased to BAT level by prolonged stimulation. Ex vivo measurements recapitulated the PET findings, and measured 18 F-FDG uptake in other WAT depots was similar to inguinal WAT. WAT browning by prolonged stimulation was confirmed by a substantial increase in uncoupling protein 1 (UCP1), cytochrome-c oxidase 4 (COX4), and PR domain containing 16 (PRDM16) staining as markers of brown adipocytes. UCP1 content, which served as a measure for extent of browning, was low in baseline inguinal WAT but linearly increased over 10 d of CL316,243 injection. Finally, image-based and ex vivo-measured 18 F-FDG uptake in inguinal WAT correlated well with UCP1 content. Conclusion: 18 F-FDG PET/CT has the capacity to monitor brown adipocyte recruitment into WAT depots in vivo and may thus be useful for screening the efficacy of strategies to promote WAT browning. Subcut aneous and visceral white adipose tissue (WAT) contributes to obesity by storing excess energy as intracellular lipid (1,2). By contrast, brown adipose tissue (BAT) can have a negative influence on weight gain by dissipating energy as heat (3,4). This thermoregulatory response is mediated through norepinephrineactivated b3 adrenergic receptor (b3AR) signaling. The exciting recent revelation that functional BAT is present not only in animals and young children but also in human adults (5,6) has fueled attempts to exploit its energy-consuming property to counter obesity (7,8). Unfortunately, however, obese patients have insufficient amounts of BAT, limiting the value of constitutive BAT for weight reduction (9).On the other hand, obese subjects have abundant amounts WAT. It has recently become known that WAT can recruit clusters of adipocytes with a brownlike phenotype. This process, called WAT browning, can be seen in mice stimulated by prolonged cold exposure or by b3AR agonists as a mimetic of cold stress (10,11). Brownlike cells recruited by WAT browning are referred to as beige (pale brown) adipocytes (12)(13)...