18F-FDG Accumulation Research Articles

Intense accumulation of 18F-FDG, not enhancement on MRI, helps to guide the surgical biopsy accurately in soft tissue tumors

Soft tissue sarcomas are a highly heterogeneous group of malignancies that arise from mesenchymal tissues. Grading of soft tissue sarcomas is an important prerequisite for the choice of therapy and estimation of prognosis. However, incisional biopsy of huge soft tissue sarcoma lesions frequently fails to provide an accurate diagnosis when there is a benign component, cystic changes and/or necrosis. MRI is helpful in evaluating the extent of the sarcoma lesion, vascularization, invasiveness and integrity of surrounding tissue, but definitive differentiation of benignity and malignancy is not possible with it. In this study, positron emission tomography using [(18)F]-2-fluoro-2-deoxy-D-glucose successfully guided surgeons to identify the most hypermetabolic and, therefore, the most suitable biopsy sites of huge soft tissue sarcoma.

18F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

It is hoped that in the not too distant future, noninvasive imaging-based molecular interrogation and characterization of tumors can improve our fundamental understanding of the dynamic biologic behavior of cancer. For example, the new dimension of diagnostic information that is provided by (18)F-FDG PET has led to improved clinical decision making and management changes in a substantial number of patients with cancer. In this context, the aim of this review is to bring together and summarize the current data on the correlation between the underlying molecular biology and the clinical observations of tumor (18)F-FDG accumulation in 3 major human cancers: lung, breast, and colon.

Comparison of 18F-FET and 18F-FDG PET in brain tumors

The purpose of this study was to compare the diagnostic value of positron emission tomography (PET) using [(18)F]-fluorodeoxyglucose ((18)F-FDG) and O-(2-[(18)F]fluoroethyl)-l-tyrosine ((18)F-FET) in patients with brain lesions suspicious of cerebral gliomas. Fifty-two patients with suspicion of cerebral glioma were included in this study. From 30 to 50 min after injection of 180 MBq (18)F-FET, a first PET scan ((18)F-FET scan) was performed. Thereafter, 240 MBq (18)F-FDG was injected and a second PET scan was acquired from 30 to 60 min after the second injection ((18)F-FET/(18)F-FDG scan). The cerebral accumulation of (18)F-FDG was calculated by decay corrected subtraction of the (18)F-FET scan from the (18)F-FET/(18)F-FDG scan. Tracer uptake was evaluated by visual scoring and by lesion-to-background (L/B) ratios. The imaging results were compared with the histological results and prognosis. Histology revealed 24 low-grade gliomas (LGG) of World Health Organization (WHO) Grade II and 19 high-grade gliomas (HGG) of WHO Grade III or IV, as well as nine others, mainly benign histologies. The gliomas showed increased (18)F-FET uptake (>normal brain) in 86% and increased (18)F-FDG uptake (>white matter) in 35%. (18)F-FET PET provided diagnostically useful delineation of tumor extent while this was impractical with (18)F-FDG due to high tracer uptake in the gray matter. A local maximum in the tumor area for biopsy guidance could be identified with (18)F-FET in 76% and with (18)F-FDG in 28%. The L/B ratios showed significant differences between LGG and HGG for both tracers but considerable overlap so that reliable preoperative grading was not possible. A significant correlation of tracer uptake with overall survival was found with (18)F-FDG only. In some benign lesions like abscesses, increased uptake was observed for both tracers indicating a limited specificity of both techniques. (18)F-FET PET is superior to (18)F-FDG for biopsy guidance and treatment planning of cerebral gliomas. The uptake of (18)F-FDG is associated with prognosis, but the predictive value is limited and a histological evaluation of tumor tissue remains necessary. Therefore, amino acids like (18)F-FET are the preferred PET tracers for the clinical management of cerebral gliomas.

Inflammatory Cytokines and Hypoxia Contribute to 18F-FDG Uptake by Cells Involved in Pannus Formation in Rheumatoid Arthritis

Assessment of the activity of rheumatoid arthritis (RA) is important for the prediction of future articular destruction. (18)F-FDG PET is known to represent the metabolic activity of inflammatory disease, which correlates with the pannus volume measured by MRI or ultrasonography. To evaluate the correlation between (18)F-FDG accumulation and RA pathology, we assessed (18)F-FDG accumulation in vivo using collagen-induced arthritis (CIA) animal models and (3)H-FDG uptake in vitro using various cells involved in arthritis. (18)F-FDG PET images of rats with CIA were acquired on days 10, 14, and 17 after arthritis induction. The specimens were subsequently subjected to macroautoradiography, and the (18)F-FDG accumulation was compared with the histologic findings. (3)H-FDG uptake in vitro in inflammatory cells (neutrophils, macrophages, T cells, and fibroblasts) was measured to evaluate the contributions of these cells to (18)F-FDG accumulation. In addition, the influence on (3)H-FDG uptake of inflammatory factors, such as cytokines (tumor necrosis factor alpha [TNFalpha], interleukin 1 [IL-1], and IL-6), and hypoxia was examined. (18)F-FDG PET depicted swollen joints, and (18)F-FDG accumulation increased with the progression of arthritis. Histologically, a higher level of (18)F-FDG accumulation correlated with the pannus rather than the infiltration of inflammatory cells around the joints. In the in vitro (3)H-FDG uptake assay, fibroblasts showed the highest (3)H-FDG uptake, followed by neutrophils. Although only a small amount of (3)H-FDG was incorporated by resting macrophages, a dramatic increase in (3)H-FDG uptake in both fibroblasts and macrophages was observed when these cells were exposed to inflammatory cytokines, such as TNFalpha and IL-1, and hypoxia. Although neutrophils showed relatively high (3)H-FDG uptake without activation, no increase in (3)H-FDG uptake was observed in response to inflammatory cytokines. (3)H-FDG uptake by T cells was much lower than that by other cells. Thus, fibroblasts and activated macrophages contribute to a high level of (18)F-FDG accumulation in the pannus, and hypoxia as well as cytokine stimulation significantly increases (18)F-FDG uptake by these cells. (18)F-FDG accumulation in RA reflects proliferating pannus and inflammatory activity enhanced by inflammatory cytokines and hypoxia. (18)F-FDG PET should be effective for quantifying the inflammatory activity of RA.

Gastrointestinal 18F-FDG accumulation on PET without a corresponding CT abnormality is not an early indicator of cancer development

Focal gastrointestinal 2-deoxy-2-[(18)F]-fluoro-D: -glucose (FDG) uptake can frequently be found on FDG-PET/CT even in patients without known gastrointestinal malignancy. The aim of this study was to evaluate whether increased gastrointestinal FDG uptake without CT correlate is an early indicator of patients developing gastrointestinal malignancies. A total of 1,006 patients without esophagogastric or anorectal malignancies underwent FDG-PET/CT. The esophagogastric junction, the stomach and the anorectum were evaluated for increased FDG uptake. Patients without elevated uptake were assigned to group A, patients with elevated uptake were allocated to group B. The SUVmax values of both groups were tested for significant differences using the U test. A follow-up of longer than 1 year (mean 853 +/- 414 days) served as gold standard. A total of 460 patients had to be excluded based on insufficient follow-up data. For the remaining 546 patients the mean SUVmax was as follows: (a) esophagogastric junction, group A 3.1 +/- 0.66, group B 4.0 +/- 1.11, p < 0.01; (b) stomach, group A 2.8 +/- 0.77, group B 4.1 +/- 1.33, p < 0.01; (c) rectal ampulla, group A 2.8 +/- 0.83, group B 3.9 +/- 1.49, p < 0.01; (d) anal canal, group A 2.7 +/- 0.55, group B 3.9 +/- 1.59, p < 0.01. Only one patient developed gastric cancer. In the case of an unremarkable CT, elevated esophagogastric or anorectal FDG uptake does not predict cancer development and does not have to be investigated further.

18F-FDG PET for Semiquantitative Evaluation of Acute Allograft Rejection and Immunosuppressive Therapy Efficacy in Rat Models of Liver Transplantation

Acute allograft rejection remains a major complication after liver transplantation. We report a semiquantitative imaging method of detecting acute allograft rejection with (18)F-FDG PET. Syngeneic and allogeneic transplanted rats, with or without immunosuppressive treatment, were subjected to serial PET. Autoradiography of the liver was conducted in both the syngeneic and the allogeneic rats. A significant increment of (18)F-FDG accumulation in liver allografts was observed by PET on day 2. The (18)F-FDG signal was concentrated in the area where inflammatory cells around the vessels were detected by autoradiography. Allotransplanted rats treated with an immunosuppressive agent displayed a marked decrease in hepatic (18)F-FDG uptake, compared with allotransplanted rats that were not treated. (18)F-FDG PET may be a valid method for facilitating the development of protocols to diagnose graft rejection and to monitor the efficacy of immunosuppressive therapy.

PET and Macro- and Microautoradiographic Studies Combined with Immunohistochemistry for Monitoring Rat Intestinal Ulceration and Healing Processes

18F-FDG PET is used mainly in clinical settings for imaging focal cancer sites, but the usefulness of the modality in imaging gastrointestinal ulcers has not been established. We investigated whether PET can be used for noninvasive monitoring of indomethacin-induced small-intestine ulceration. Intestinal ulcers were induced in rats by subcutaneous administration of indomethacin. An 18F-FDG PET scan was obtained at 1, 2, and 7 d after indomethacin administration. 18F-FDG uptake in the small intestine was quantified by gamma-counting, and macro- and microautoradiographic studies were performed to determine the site of 18F-FDG uptake in tissue and at the cellular level. Ulcers observed in the intestine (mainly in the ileum) 1-4 d after indomethacin administration were most severe at 1 d after administration and were almost healed at day 7. The PET study showed increased 18F-FDG uptake in the intestine correlating to the severity of ulceration, returning to the basal level on day 7. Ex vivo imaging and gamma-counting showed that these regions of high uptake corresponded to regions of ulceration. A microautoradiographic study combined with immunohistochemistry revealed heavy accumulation of 18F-FDG in inflammatory cells containing peroxidase on day 1 and in cells forming granulation tissue (alpha-smooth muscle actin-positive myofibroblasts and ED2-positive macrophages) on days 2-4 in and around ulcers. Proliferating (Ki67-immunopositive) intestinal crypt cells were also densely labeled with 18F-FDG in intact intestinal tissue taken from the indomethacin-treated and the control animals. Our experimental data suggest that 18F-FDG PET may be useful for evaluating the occurrence of small-intestine ulcers. Ulceration could be visualized early by the prominent uptake of 18F-FDG by inflammatory cells and by the formation of granulation tissue by cells in and around ulcers.

Kinetic analysis of experimental rabbit tumour and inflammation model with 18F-FDG PET/CT

Non-specific accumulation of 18F-FDG by both tumour and inflammatory lesions can make diagnostic analysis difficult. Our aim was to explore the difference in 18F-FDG uptake kinetics between tumour and inflammatory cells. To this end, we investigated VX2 tumour lesions and inflammatory lesions in rabbits. Six rabbits with VX2 tumour cells transplanted into one forelimb muscle and inflammatory lesions induced by turpentine oil in the contralateral forelimb were scanned for 60 minutes post 18F-FDG injection. Imaging data was analyzed with the standard 2-tissue-compartment model. Parameters, VB, Ki, K1, k2, k3, k4, were compared between tumour and inflammatory lesions. SUV and dual time scan methods were also compared in the experiment. Time activity curves of VX2 tumour lesions showed a characteristic pattern of gradually increasing 18F-FDG uptake up to 60 min, whereas, 18F-FDG uptake in inflammatory lesions increased more slowly than in tumours. Parameters estimated from the uptake process showed that forward transport constant, K1, and influx constant, Ki, values in VX2 tumour lesions (0.186 +/- 0.053 and 0.048 +/- 0.014, respectively) was significantly higher than that in inflammatory lesions (0.129 +/- 0.024 and 0.022 +/- 0.007, respectively) (p < 0.05). In contrast, mean values of VB, k2, k3 and k4 derived from VX2 tumours were not significantly different from that of inflammatory lesions. SUVs at 60 minutes post 18F-FDG injection were also significantly higher in the VX2 tumor lesions than in the inflammatory lesions. Retention index (RI) was not significantly different between VX2 tumours and inflammatory lesions (1.134 +/- 0.076 vs. 1.060 +/- 0.058, p > 0.05). Different kinetic parameters (Ki, K1, k3) exist between inflammatory and tumour lesions.

18F-FDG PET analysis of schwannoma: increase of SUVmax in the delayed scan is correlated with elevated VEGF/VPF expression in the tumors

In order to clarify the increased 2-deoxy-2-fluoro-(18)F-D: -glucopyranose ((18)F-FDG) accumulation in schwannoma by positron emission tomography (PET) analysis, immunohistochemical analysis for the factors involved in glucose transportation and vascular formation was performed. Twenty-six patients with schwannoma (13 men and 13 women) with ages ranging from 27 to 75 years, who received whole body (18)F-FDG PET scan, were enrolled for the present study. The retention index (RI) was calculated by dividing the increase in the standardized uptake value (SUVmax) at the delayed scan by the SUVmax in the early scan. SUVmax and RI were compared with the histologic variables, including the expression of glucose transporters 1 and 3, hexokinase II, vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), and microvascular density shown by CD31 immunohistochemistry. Mean SUVmax values in the early and delayed scans were 2.64 +/- 1.47 and 2.71 +/- 1.57 (mean +/- SD), respectively. RI was -2.5 +/- 21 (percentage). SUVmax showed a positive correlation with the tumor size (tumor size <5 cm, 2.06 +/- 0.72; >5 cm, 3.95 +/- 1.89; p < 0.05) and the microvascular density (negative density, 2.16 +/- 1.12; positive density, 3.56 +/- 1.67; p < 0.05). RI correlated with VEGF/VPF expression in the tumors (negative expression, -11 +/- 6.1; positive expression, 13 +/- 8.1; p < 0.05). Other factors showed no correlation with SUVmax or RI. Microvascular density and vascular permeability of the tumor are suggested to affect the enhanced (18)F-FDG accumulation in schwannoma.

High 18F-FDG Uptake in Synthetic Aortic Vascular Grafts on PET/CT in Symptomatic and Asymptomatic Patients

Graft infection is a serious complication to vascular surgery. The aim of this study was to assess (18)F-FDG uptake in vascular grafts in patients with or without symptoms of graft infection. In all 2,045 patients examined by PET/CT at our clinic, 16 patients with synthetic aortic grafts were identified and reevaluated for (18)F-FDG accumulation. Clinical and biochemical data were obtained from patient records. High (18)F-FDG uptake was found in 10 of 12 grafts in the patients who underwent open surgery and in 1 of 4 grafts in patients who underwent endovascular aneurysm repair. On the basis of biochemical and clinical data, it was concluded that 1 of the 16 patients had a graft infection at the time of investigation. (18)F-FDG uptake in vascular grafts was found in the vast majority of patients without graft infection. The risk of a false-positive diagnosis of graft infection by (18)F-FDG PET/CT is evident.

Prolonged High-Fat Feeding Enhances Aortic 18F-FDG and 99mTc-Annexin A5 Uptake in Apolipoprotein E-Deficient and Wild-Type C57BL/6J Mice

(18)F-FDG, a marker of the enhanced metabolism characteristic of activated inflammatory cells, and (99m)Tc-annexin A5, a marker of apoptosis, are both widely believed to be useful for the imaging of unstable atheroma (rupture-prone vulnerable plaques [VP]). Serum cholesterol functions as a proinflammatory factor, driving the formation of VP, and affects the immune responses of aortic tissues systemically. It is therefore reasonable to postulate that prolonged cholesterol loading may alter the aortic uptake of these tracers. Here, we evaluated the aortic uptake of (18)F-FDG and (99m)Tc-annexin A5 in apolipoprotein E-deficient (apoE(-/-)) and wild-type mice placed on high-fat diets. Male apoE(-/-) and wild-type (C57BL/6J) mice were maintained on high-fat diets after the age of 5 wk. Wild-type mice fed regular chow were used as controls. At the ages of 10, 18, and 25 wk (5-15 mice per group at each time point), mice were injected with (18)F-FDG or (99m)Tc-annexin A5 after 12 h of fasting. At 1 h after (18)F-FDG injection (or 2 h after (99m)Tc-annexin A5 injection), mice were sacrificed, and the aortas were removed for well-type scintillation counting of radioactivity. The results were expressed as percentage injected dose per gram of tissue and normalized by animal body weight [(ID%/g) x kg]. En face staining was then performed to assess the location and size (surface area) of the lipid pool within each aortic specimen. Concurrent blood samples were obtained to determine the plasma lipid profile of each group. No atherosclerotic lesions were found in wild-type mice regardless of the diet, whereas the lesion area progressively increased with age in apoE(-/-) mice. Mean plasma cholesterol levels remained stable with the regular diet in wild-type mice (73-78 mg/dL) but increased with cholesterol feeding in wild-type mice (143-179 mg/dL) and in apoE(-/-) mice (>1,300 mg/dL). Aortic tracer uptake [(ID%/g) x kg] remained stable with the regular diet in wild-type mice (0.054-0.053 and 0.021-0.023 for (99m)Tc-annexin A5) but increased with cholesterol feeding in wild-type mice (0.164 for (18)F-FDG and 0.036 for (99m)Tc-annexin A5 at 25 wk) and in apoE(-/-) mice (0.249 for (18)F-FDG and 0.047 for (99m)Tc-annexin A5 at 25 wk). The accumulation of (18)F-FDG and (99m)Tc-annexin A5 in aortic tissues is influenced not only by the progression of atherosclerotic disease but also by cholesterol loading over time.

18F-FDG accumulation in the oral cavity is associated with periodontal disease and apical periodontitis: an initial demonstration on PET/CT

The objective of this study was to prospectively investigate the relationship between high accumulation of 2-deoxy-2-[(18)F] fluoro-D: -glucose (FDG) in the oral cavity and dental infections on positron emission tomography/computed tomography (PET/CT). FDG-PET/CT scans of 103 patients who underwent a health screening were evaluated. The dental examination was performed prior to each PET/CT scan, and dental infections were assessed. Dental infections were classified into six blocks. The severity of dental caries was classified into five grades, and periodontal disease and apical periodontitis were classified into three grades. Two radiologists classified the PET images in the same manner as the dental examination. They evaluated the intensity of FDG uptake by a four-point visual PET image score for each block. The comparison of the dental examination, as a gold standard, and the visual PET image score was performed on a patient or block basis. On a patient-based analysis, 21 of 103 patients (20.4%) showed PET positive findings in the oral cavity; 18 of the 21 patients (85.7%) had dental infections. On a block-based analysis, 25 of 605 blocks (4.1%) showed PET positive findings in the oral cavity; 22 of the 25 blocks (88.0%) had dental infections. On a detailed block-based analysis, a significant difference was observed between the presence of periodontal disease, or apical periodontitis and the positivity of the visual PET image findings (P < 0.01). Their severity correlated with the visual PET image score (P < 0.05). Periodontal disease or apical periodontitis, but not dental caries, caused FDG accumulation in the oral cavity. This finding should be taken into account when a head and neck FDG-PET study is interpreted.

18F-FDG Uptake in Reactive Neck Lymph Nodes of Oral Cancer: Relationship to Lymphoid Follicles

PET using (18)F-FDG is acceptable as a preoperative diagnostic tool for head and neck cancer. PET combined with CT provides precise localization of neck lymph nodes. Reactive lymphadenopathy is well known as a principal cause of false-positive findings on PET/CT for nodal staging. We investigated the reactive lymph nodes of oral cancer to elucidate the (18)F-FDG-avid area in these nodes. Surgically dissected neck lymph nodes of oral cancer were retrospectively reviewed. Of the patients without pathologic nodal metastasis who underwent preoperative PET/CT, 11 patients with 31 enlarged lymph nodes at 20 levels were enrolled. The maximum standardized uptake value (SUVmax) of each lymph node was recorded. The diameters of the long and short axes were measured by pathologic sectioning, and the sectional surface area was calculated in square millimeters. Besides being stained with hematoxylin and eosin, the sections were immunohistochemically stained by CD79a for B cells, CD3 for T cells, CD68 for macrophages, CD21 for follicular dendritic cells (FDCs), and ubiquitous glucose transporter type 1 (GLUT1). The expression of GLUT1 was compared with staining of lymphoid cells. The numbers of total lymphoid follicles and hyperplastic secondary follicles were counted on CD21 and hematoxylin and eosin sections, respectively. The follicular reactivity index was determined as the ratio of secondary follicles relative to total follicles on the corresponding section. These parameters of reactive lymph nodes were analyzed on a level basis. GLUT1 was expressed exclusively in lymphoid follicles, whose staining pattern was identical to that of FDCs. The calculated sectional area correlated significantly with the number of total follicles (r = 0.560; P = 0.0101). SUVmax did not correlate with the number of total follicles (P = 0.8947) but correlated significantly with the number of secondary follicles (r = 0.535; P = 0.0152). In addition, a strong positive correlation between SUVmax and the follicular reactivity index was demonstrated (r = 0.829; P < 0.0001). GLUT1 was expressed on cytoplasmic protrusions of FDCs in lymphoid follicles. The (18)F-FDG accumulation in reactive lymphadenopathy depended on secondary follicles. FDCs in germinal centers of secondary follicles are suggested to be avid for (18)F-FDG and the principal cause of false-positive findings for nodal staging.

Utility of 18FDG-PET for differentiating the grade of malignancy in thymic epithelial tumors

The objective of this study was to assess the value of (18)F-FDG PET in thymic epithelial tumors according to the WHO histologic classification and to evaluate its potential for differentiating the grade of malignancy in thymic epithelial tumors. Thirty-six patients with a thymic epithelial tumor who underwent (18)F-FDG PET examination before treatment were enrolled in the present study. The T/M ratio, which is the ratio of the peak standardized uptake value (SUV) of the tumor to the mean SUV of mediastinum, was compared in subgroups of a simplified WHO histological classification; low-risk thymoma (Types A, AB and B1), high-risk thymoma (Types B2 and B3), and thymic carcinoma. Tumors included 15 low-risk thymomas, 10 high-risk thymomas and 11 thymic carcinomas. Upon visual inspection, all tumors showed (18)F-FDG accumulation and the mean T/M ratio in these three subgroups was 2.64, 4.29 and 8.90, respectively. The differences between the three subgroups were statistically significant (low-risk vs. high-risk: p=0.01, high-risk vs. thymic carcinoma: p=0.01). A significant relationship was seen between (18)F-FDG PET accumulation and histologic subtype in thymic epithelial tumors when they were classified into three groups. PET may be useful for predicting the grade of malignancy in thymic epithelial tumors.

Preclinical Efficacy of the c-Met Inhibitor CE-355621 in a U87 MG Mouse Xenograft Model Evaluated by18F-FDG Small-Animal PET

The purpose of this study was to evaluate the efficacy of CE-355621, a novel antibody against c-Met, in a subcutaneous U87 MG xenograft mouse model using (18)F-FDG small-animal PET. CE-355621 or control vehicle was administered intraperitoneally into nude mice (drug-treated group, n = 12; control group, n = 14) with U87 MG subcutaneous tumor xenografts. Drug efficacy was evaluated over 2 wk using (18)F-FDG small-animal PET and compared with tumor volume growth curves. The maximum %ID/g (percentage injected dose per gram of tissue) of (18)F-FDG accumulation in mice treated with CE-355621 remained essentially unchanged over 2 wk, whereas the %ID/g of the control tumors increased 66% compared with the baseline. Significant inhibition of (18)F-FDG accumulation was seen 3 d after drug treatment, which was earlier than the inhibition of tumor volume growth seen at 7 d after drug treatment. CE-355621 is an efficacious novel antineoplastic chemotherapeutic agent that inhibits (18)F-FDG accumulation earlier than tumor volume changes in a mouse xenograft model. These results support the use of (18)F-FDG PET to assess early tumor response for CE-355621.

PET/CT in Malignant Bone Disease

The most commonly used positron emission tomography (PET) tracer in clinical practice, fluorine-18 fluorodeoxyglucose ( (18)F-FDG) is a glucose analogue that directly gains entry in excess into tumor cells. It is therefore sensitive for the detection of early bone marrow involvement prior to any identifiable bone changes. The introduction of (18)F-FDG-PET in the imaging algorithms of various malignant diseases often obviates the need to perform a separate assessment of malignant bone involvement with conventional bone scintigraphy. After therapy, disappearance of (18)F-FDG accumulation indicates success even when the bone remains morphologically abnormal. Novel hybrid systems composed of PET and computed tomography (CT) allow for acquisition of both modalities in the same clinical setting and the generation of fused functional-anatomical images. This technique has been found to improve the diagnostic accuracy of PET in detecting malignant bone involvement. This article discusses the role of PET/CT, primarily (18)F-FDG PET/CT, in the assessment of malignant bone involvement in patients with primary bone sarcomas, common solid malignancies, lymphoma, and multiple myeloma.

PET/CT evaluation of the physiologic accumulation of 18F-FDG within the gallbladder vesicle

The aim of this study was to investigate physiological fluorine 18-labeled fluourodeoxyglucose accumulation in the gallbladder (GB) during clinical positron emission tomography (PET) examinations. Three patient groups were included. In Group 1, nine patients with higher fluourodeoxyglucose (FDG) accumulation in the GB than in the liver were examined, followed up and finally diagnosed. In Group 2, the correlations between FDG GB accumulation and various parameters in 286 patients were investigated. In Group 3, changes in FDG GB accumulation between early and delayed PET scans were analyzed in 12 patients. In Group 1, all nine patients who exhibited a high FDG GB accumulation had no evidence of GB disease. In Group 2, FDG GB accumulation was significantly correlated with the injection-scan time interval and inversely correlated with the GB size index. Group 3 showed a significant increase in FDG accumulation in the GB on delayed PET scans, compared with that seen on early scans. In clinical PET studies, FDG accumulation within the GB is infrequently observed but may be due to FDG excretion into the bile. Recognition of this phenomenon may be important to avoid misdiagnosing physiological GB FDG accumulation as indicating a pathologic status and preventing unnecessary examinations.

Effect of Nicotine and Ephedrine on the Accumulation of 18F-FDG in Brown Adipose Tissue

This study evaluated the effect of various beta-adrenergic agonists on (18)F-FDG uptake in brown adipose tissue (BAT) in rats using ex vivo biodistribution studies. Caffeine (10 mg/kg of body weight, n = 4), ephedrine (5 mg/kg of body weight, n = 4), nicotine (0.8 mg/kg of body weight, n = 9), or a mixture of nicotine and ephedrine (0.8 mg/kg of body weight and 5 mg/kg of body weight, respectively, n = 9) was injected into the peritoneal cavity of female Lewis rats 30 min before intravenous (18)F-FDG injection. One hour after injection of (18)F-FDG, the animals were sacrificed, and BAT, other major organs, and blood were extracted. The biodistribution results were compared with body temperature data. In the rats injected with nicotine or ephedrine, the mean uptake of (18)F-FDG, in percentage injected dose (%ID)/(g of interscapular BAT) x (kg of body weight), was significantly increased (7.9-fold for nicotine and 3.7-fold for ephedrine), compared to the control rats. Nicotine had the strongest effect on (18)F-FDG uptake in BAT. Caffeine increased BAT uptake slightly, but this increase did not reach statistical significance. The combination of nicotine and ephedrine increased the uptake 12.0-fold, compared with control rats; more than either nicotine or ephedrine alone. Uptake of (18)F-FDG in most other major organs did not change significantly. The effect of nicotine was blocked by prior injection of beta-adrenergic antagonists. A transient decrease in body temperature was observed in the nicotine-injected group, and this effect was canceled by prior injection of beta-adrenergic antagonists. No significant change in baseline temperature was seen before or after beta-adrenergic agonist injection. Nicotine caused a greater increase in (18)F-FDG uptake in BAT than did other interventions, and the effect was increased when nicotine was combined with ephedrine. The effect of nicotine was completely blocked by prior injection of beta-adrenergic antagonists, indicating that beta-adrenergic agonists increase the metabolism of BAT. These preclinical data suggest that patients should avoid nicotine and ephedrine before undergoing (18)F-FDG PET to minimize (18)F-FDG uptake in BAT.

Clear-PEM system counting rates: a Monte Carlo study

Positron Emission Mammography (PEM) with 18F-Fluorodeoxyglucose (18F-FDG) is a functional imaging technique for breast cancer detection. The development of dedicated imaging systems with high sensitivity and spatial resolution are crucial for early breast cancer diagnosis and an efficient therapy. Clear-PEM is a dual planar scanner designed for high-resolution breast cancer imaging under development by the Portuguese PET Mammography consortium within the Crystal Clear Collaboration. It brings together a favorable combination of high-density scintillator crystals coupled to compact photodetectors, arranged in a double readout scheme capable of providing depth-of-interaction information.A Monte Carlo study of the Clear-PEM system counting rates is presented in this paper. Hypothetical breast exam scenarios were simulated to estimate the single event rates, true and random coincidence rates. A realistic description of the patient and detector geometry, radiation environment, physics and instrumentation factors was adopted in this work. Special attention was given to the 18F-FDG accumulation in the patient torso organs which, for the Clear-PEM scanner, represent significant activity outside the field-of-view (FOV) contributing to an increase of singles, randoms and scattered coincidences affecting the overall system performance. The potential benefits of patient shielding to minimize the influence of the out-of-field background was explored. The influence of LYSO:Ce crystal intrinsic natural activity due to the presence of the 176Lu isotope on the counting rate performance of the proposed scanner, was also investigated.

Evaluation of delayed18F-FDG PET in differential diagnosis for malignant soft-tissue tumors

Positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) has been used for the evaluation of soft-tissue tumors. However, the range of accumulation of 18F-FDG for malignant soft-tissue lesions overlaps with that of benign lesions. The aim of this study is to investigate the usefulness of delayed 18F-FDG PET imaging in the differentiation between malignant and benign soft-tissue tumors. Fifty-six patients with soft-tissue tumors underwent whole body 18F-FDG PET scan at 1 hour (early scan) and additional scan at 2 hours after injection (delayed scan). The standardized uptake value (SUV(max)) of the tumor was determined, and the retention index (RI) was defined as the ratio of the increase in SUV(max) between early and delayed scans to the SUV(max) in the early scan. Surgical resection with histopathologic analysis confirmed the diagnosis. Histological examination proved 19 of 56 patients to have malignant soft-tissue tumors and the rest benign ones. In the scans of all 56 patients, there was a statistically significant difference in the SUV(max) between malignant and benign lesions in the early scan (5.50 +/- 5.32 and 3.10 +/- 2.64, respectively, p < 0.05) and in the delayed scan (5.95 +/- 6.40 and 3.23 +/- 3.20, respectively, p < 0.05). The mean RI was not significantly different between malignant and benign soft-tissue tumors (0.94 +/- 23.04 and -2.03 +/- 25.33, respectively). In the current patient population, no significant difference in the RI was found between malignant and benign soft-tissue lesions. Although the mean SUV(max) in the delayed scan for malignant soft-tissue tumors was significantly higher than that for benign ones, there was a marked overlap. The delayed 18F-FDG PET scan may have limited capability to differentiate malignant soft-tissue tumors from benign ones.