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Subjects were 45 patients with angioimmunoblastic T-cell lymphoma (AITL) who underwent 2-[ 18 F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) at baseline and interim after 2-4 cycles. Predictors of progression-free survival (PFS) and overall survival (OS) were assessed. Positive interim PET/CT (Deauville score ≥3) was a significant independent predictor of poor PFS (Hazard ratio, 4.42; p=.028), and showed marginal significance to predict OS (p=.065). Less than 60% decrease in the average change of maximum standardized uptake value normalized by lean body mass (SUL max ) also was a significant independent predictor of poor PFS (Hazard ratio, 12.96; p=.001) and poor OS (Hazard ratio, 24.11; p=.006). Interim PET/CT has a significant prognostic value for predicting PFS and OS in patients with AITL. Deauville score and percent decrease of SUL max have the potential to be useful parameter in classifying patients into good and poor responders.

Introduction: Compounds that modulate cancer cell glucose metabolism could open new opportunities for antitumor therapy and for monitoring response using (18)F-FDG PET. Genipin, a natural dietary compound that blocks uncoupling protein 2 (UCP2)-mediated mitochondrial proton leakage, is a potential anticancer agent. We investigated the effect of genipin on glucose metabolism and the mitochondrial function of cancer cells., Methods: Breast and colon cancer cells were assessed for effects of genipin on (18)F-FDG uptake. T47D breast cancer cells were further evaluated for time-dependent and dose-dependent effects on (18)F-FDG uptake, lactate release, oxygen consumption rate (OCR), reactive oxygen species (ROS) production, and mitochondrial membrane potential. The effects of UCP2 knockdown were evaluated using specific siRNA., Results: Cancer cells displayed significant reductions in (18)F-FDG uptake by genipin. T47D cells showed the greatest reduction to 32.6±1.0% of controls by 250μM genipin. The effect occurred rapidly, reaching a plateau by 1h that lasted up to 24h. The effect was dose-dependent with a half-inhibitory concentration of 60.8μM. An accompanying decrease in lactate release was consistent with reduced glycolytic flux. OCR was significantly decreased by genipin to 82.2±11.4% of controls, and ROS generation was increased to 156.7±16.0%. These effects were largely reproduced by UCP2 knockdown with specific siRNA., Conclusions: Genipin decreased cancer cell (18)F-FDG uptake by reducing both glycolytic flux and mitochondrial oxidative respiration. This effect appeared to occur by blocking the ability of UCP2 to dissipate energy and restrict ROS production through proton leakage., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Identification of tumor imaging features associated with metastatic pattern may allow better understanding of cancer dissemination. Here, we investigated how primary tumor F-fluorodeoxyglucose (FDG) avidity influences the first site of breast cancer metastasis.Subjects were 264 patients with advanced breast cancer who underwent positron emission tomography/computed tomography at diagnosis and had metastasis at presentation (n = 193) or metastatic relapse after surgery (n = 71). Primary tumor FDG avidity (maximum SUV [SUVmax] ≥10.1) was compared with histology and first metastatic sites.The most common site of first metastasis was the bone, occurring in 62.7% of patients with metastasis at presentation and 38.0% of those with metastatic relapse. First metastasis to lung occurred in 30.1% and 35.2%, and to liver in 25.4% and 15.2% of respective groups. In patients with metastasis at presentation, primary tumors were FDG avid in 98/193 cases, and this was associated with more frequent first metastasis to lung (37.8% vs 22.1%; P = 0.018). In patients with metastasis relapse, primary tumors were FDG avid in 31/71 cases, and this was associated with more frequent first metastasis to lung (48.4% vs 25.0%; P = 0.041) and liver (29.0% vs 5.0%; P = 0.008). In patients with metastasis relapse, primary tumors that were FDG avid but hormone receptor negative had more first metastasis to lung (57.9% vs 26.9%; P = 0.016).FDG-avid primary breast tumors have favored first spread to the lung and liver, which suggests that tumor cells with heightened glycolytic activity better colonize these organs.

Unlabelled: The usefulness of (18)F-FDG PET in gastric cancer recurrence is limited by low sensitivity. Given that detectability by PET is dependent on the tumor's metabolic characteristics, we tested whether the performance of PET for gastric cancer recurrence is enhanced in patients with (18)F-FDG-avid primary tumors., Methods: Three hundred sixty-eight patients with advanced gastric cancer underwent (18)F-FDG PET/CT for initial staging and for recurrence surveillance after curative surgery. On initial PET/CT, primary tumors were (18)F-FDG-avid if they displayed focal uptake with an SUVmax 4 or more. Follow-up (18)F-FDG PET/CT was evaluated for recurrent disease., Results: On initial PET/CT, the primary tumor was (18)F-FDG-avid in 236 of 368 (64.1%) and nonavid in 132 patients (35.9%). During follow-up for 18.9 ± 13.3 mo, 72 patients (19.6%) had recurrence. Of the 63 PET scans with recurrence, 42 (66.7%) and 21 (33.3%) were scans of patients with (18)F-FDG-avid and nonavid primary tumors, respectively. PET sensitivity was higher in scans of patients with (18)F-FDG-avid than nonavid tumors for all recurrences (81.0% vs. 52.4%;P= 0.018) and nonanastomosis site recurrences (82.1% vs. 47.4%; P= 0.006). The sensitivity for detecting peritoneal recurrence was also higher for the avid tumor group. PET specificity was similarly high (97.1% and 97.5%) for both groups. Adding cell type and Lauren classification to tumor(18)F-FDG avidity further enhanced PET sensitivity., Conclusion: Surveillance (18)F-FDG PET/CT after resection of gastric cancer has significantly higher sensitivity in patients with (18)F-FDG-avid primary tumors and may have greater value in this group., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Purpose: We investigated the significance of unexpected focal pyriform sinus FDG uptake and determined the ability of PET/CT parameters to identify malignancy., Materials and Methods: FDG PET/CT reports of 56,585 consecutive subjects were retrospectively reviewed, and 281 cases (0.50%) with focal pyriform sinus uptake were included. PET images were assessed for maximum standardized uptake values (SUVmax) and asymmetric indices of FDG activity, and CT images were evaluated for pyriform sinus narrowing. The final diagnosis was determined by tissue biopsy, laryngoscopy, radiological findings, and clinical follow-up., Results: Among the 281 subjects, final diagnosis was pyriform sinus malignancy in 29 (10.3%) and benignity in 215 cases (76.5%). Malignant lesions had significantly higher SUVmax (9.13 ± 3.64 vs. 3.53 ± 1.01) and asymmetric index (4.16 ± 1.81 vs. 1.54 ± 0.39) compared to benign causes. Patients with malignant lesions also had higher cervical lymph node SUVmax (6.66 ± 8.79 vs. 2.76 ± 2.46, all P < 0.001). Lesion SUVmax ≥4.24 identified malignancy with a sensitivity of 93.1% and specificity of 86.5%. Asymmetric index ≥1.81 had a sensitivity of 100% and specificity of 89.7%., Conclusion: Incidentally identified focal pyriform sinus uptake on FDG PET/CT should be evaluated for possible malignancy in the presence of high SUVmax or asymmetric index.

Unlabelled: 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 = 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 = 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.

Objective: We investigated the clinical significance of incidental diffuse thyroid uptake (DTU) on (18)F-FDG PET in subjects without a history of cancer., Materials and Methods: This study included 2062 studies from adults who underwent (18)F-FDG PET as a cancer screening program. Subjects were divided into the following two groups: with (group I) or without (group II) DTU. The presence of DTU and the thyroid visual grading score were compared with thyroid function tests, serum anti-microsomal antibody (AMA) levels, and the presence of diffuse parenchymal change (DPC) on ultrasonography (USG)., Results: DTU was found in 6.6% of the scans (137/2062). Serum thyroid stimulating hormone (TSH) and AMA levels were significantly higher in group I than in group II. Increased AMA level (55.1%) and DPC (48.7%) were more frequently found in group I (p < 0.001). The proportion of subjects with any abnormal results in serum free thyroxine, triiodothyronine, TSH, or AMA levels or DPC on USG was significantly higher in group I than in group II (71.5% vs. 10.6%, p < 0.001), and was significantly and gradually increased according to the visual grading score group (0 vs. 1-2 vs. 3-4 = 10.6% vs. 58.5% vs. 90.9%, p < 0.001). TSH and is AMA levels were significantly increased according to the visual grading score., Conclusion: The presence or degree of incidental DTU on (18)F-FDG PET is closely correlated with increased serum AMA and TSH levels, and the presence of DPC on USG. Therefore, the most plausible pathological cause of DTU may be cell damage by an autoimmune mechanism.

Background: The role of (18) F-fluorodeoxyglucose positron emission tomography/computed tomography ((18) F-FDG PET/CT) in evaluating pulmonary artery lesions has not yet been established. The purpose of this study is to evaluate the usefulness of (18) F-FDG PET/CT imaging in differentiating malignant from benign pulmonary artery (PA) lesions., Methods: In this retrospective study, 18 subjects with 26 low-attenuated filling defects suspicious for PA malignancy on contrast-enhanced chest CT were enrolled; all of whom subsequently underwent (18) F-FDG PET/CT. The maximum standardized uptake value (SUVmax) for all PA lesions, defined as the (18) F-FDG uptake, was measured. The final diagnosis was then determined by pathological findings, follow-up chest CT or clinical follow-up, and compared with the PET imaging., Results: In total, 6 PA sarcomas, 5 tumour embolism, and 15 pulmonary thromboembolism (PTE) occurred in this cohort. Not only was the SUVmax of the malignant PA lesions (10.2 ± 10.8) was significantly higher than that associated with PTE (1.7 ± 0.3; P < 0.001), no overlap occurred between groups. Conversely, no statistically significant difference in SUVmax occurred between PA sarcomas (12.8 ± 14.7) and tumour embolism (7.0 ± 1.32; P = 1.000)., Conclusions:  (18) F-FDG PET/CT is a useful imaging modality for differentiating malignant from benign PA lesions in patients with inconclusive low-attenuation filling defects on contrast-enhanced chest CT., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

Objective: We compared the prognostic value of volume-based metabolic parameters determined using fluorine 18 (F) fluorodeoxyglucose (FDG) positron emission tomography (PET) (F-FDG PET) (with other prognostic parameters in uterine cervical cancer., Methods: The subjects were 73 female patients who had an initial diagnosis of uterine cervical cancer and who underwent F-FDG PET. Various metabolic or volume-based PET parameters including maximum and average standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) were measured in primary cervical tumors. Survival analysis for disease-free survival or progression-free survival was performed with a Kaplan-Meier method using PET parameters and other clinical variables. For determining independent prognostic factors, Cox regression analysis was performed., Results: Recurrence or disease progression occurred in 23 patients (31.5%). In univariate analysis, patient age (cutoff, 57 years, P < 0.05), International Federation of Gynecology and Obstetrics stage (P = 0.07), primary tumor size (cutoff, 6.7 cm; P < 0.05), lymph node status on PET (P < 0.005), treatment method (P < 0.01), metabolic tumor volume (cutoff, 82 cm; P = 0.001), and TLG (cutoff, 7600; P = 0.005) were significant predictors of recurrence or progression. In multivariate analysis, both lymph node status on PET (hazard ratio, 1.042 [negative vs intrapelvic metastasis only], 7.008 [negative vs extrapelvic metastasis]; P < 0.001) and TLG (cutoff, 7600; hazard ratio, 2.981; P < 0.05) were independent prognostic factors for predicting recurrence., Conclusions: In uterine cervical cancer, TLG, a volume-based metabolic parameter, and lymph node status on PET may be significant independent prognostic factors for event-free survival.

Unlabelled: The purpose of this study was to identify the incidence and clinical significance of incidental pituitary uptake on whole-body (18)F-FDG PET/CT., Methods: We evaluated 13,145 consecutive subjects who underwent (18)F-FDG PET/CT. The final diagnosis of pathologic or physiologic uptake was based on brain MRI and follow-up PET scanning. Receiver-operating-characteristic curve analysis was performed to determine an optimal cutoff for detecting pathologic uptake., Results: We found that 107 (0.8%) subjects showed incidental pituitary uptake. In 29 of 71 subjects with the final diagnosis, the pituitary uptake was pathologic: macroadenomas (n = 21), microadenomas (n = 5), and malignancy (n = 3). When a maximum standardized uptake value of 4.1 was used as an optimal criterion for detecting pathologic uptake, the diagnostic sensitivity, specificity, and accuracy were 96.6%, 88.1%, and 91.5%, respectively., Conclusion: Although incidental pituitary uptake is an unusual finding, the degree of (18)F-FDG accumulation is helpful in identifying pathologic pituitary lesions that warrant further diagnostic evaluation.

Unlabelled: Small-animal PET has opened the way for imaging (18)F-FDG uptake in murine tumor models, but the need for anesthesia raises concern over its potential influence on (18)F-FDG kinetics. We thus investigated such effects on cultured cells and on tumor-bearing mice after short- and long-term fasting., Methods: Lewis lung carcinoma (LLC) cells and cardiomyoblasts were treated for 2 h with a 100 micromol/L concentration of xylazine, ketamine, xylazine plus ketamine (Xy/Ke), or pentobarbital and were measured for (18)F-FDG uptake. LLC tumor-bearing C57BL6 mice that had been kept fasting for either 4 or 20 h were injected with Xy/Ke, pentobarbital, or saline and were administered 1.8 MBq of (18)F-FDG 15 min later. Biodistribution studies and plasma glucose and insulin assays were performed 45 min after injection. Separate anesthetized and control mice underwent (18)F-FDG PET., Results: (18)F-FDG uptake in LLC cells was unaffected by anesthetic agents, whereas xylazine and ketamine caused a small increase of uptake in cardiomyoblasts. In mice kept fasting 4 h, Xy/Ke induced a marked elevation of (18)F-FDG activity (percentage injected dose [%ID]) in blood (6.8 +/- 0.9%ID/g vs. 1.1 +/- 0.6%ID/g) and kidneys while decreasing myocardial uptake (2.3 +/- 1.3%ID/g vs. 4.7 +/- 1.8%ID/g). Target-to-blood ratios were significantly reduced. Pentobarbital caused a moderate increase in blood activity (2.5 +/- 0.8%ID/g), decreased myocardial uptake (2.8 +/- 0.5%ID/g), and reduced target-to-blood ratios. PET images of mice kept fasting 4 h were consistent with the biodistribution data. Insulin levels were lower with Xy/Ke and higher with pentobarbital. In mice kept fasting 20 h, Xy/Ke and pentobarbital increased blood (18)F-FDG activity (5.5 +/- 2.2 and 4.9 +/- 0.9%ID/g vs. 2.4 +/- 0.3%ID/g) and reduced target-to-blood ratios, but these changes were substantially attenuated, compared with those in mice kept fasting 4 h. In addition, insulin levels were low and unaffected by anesthesia., Conclusion: Xy/Ke anesthesia markedly elevates blood (18)F-FDG activity and reduces tumor uptake ratios through inhibition of insulin release in mice kept fasting 4 h, whereas pentobarbital induces a similar but less severe response through insulin resistance. These metabolic effects, however, are substantially attenuated after 20 h of fasting. Hence both the choice of anesthetic and the duration of fasting have important effects on (18)F-FDG kinetics and PET images of tumor-bearing mice and should be considered when such studies are performed.

Objective: While respiratory burst enhances neutrophil glucose utilization, many neutrophil functions are critically influenced by extracellular matrix interaction and phosphoinositide-3-OH kinase (PI3K) signaling. We thus evaluated the role of RGD integrin occupancy and PI3K inhibition on respiratory burst and [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake of stimulated neutrophils., Methods: Human neutrophils were stimulated by 100 ng/ml phorbol-myristate-acetate (PMA), and respiratory burst was measured by cumulative luminescence with lucigenin. [(18)F]FDG uptake and total hexokinase activity was measured 20 min after PMA stimulation in the presence or absence of soluble RGD peptides (200 microg/ml) and/or the PI3K inhibitor wortmannin (200 nM)., Results: Phorbol-myristate-acetate induced a 71.7+/-0.9 fold increase in neutrophil oxygen intermediate generation. [(18)F]FDG uptake was increased to 194.6+/-3.7% and hexokinase activity to 145.0+/-2.0% of basal levels (both P<.0005). RGD peptides attenuated respiratory burst activation to 35.6+/-0.2% (P<.005) but did not inhibit stimulated [(18)F]FDG uptake or hexokinase activity. In contrast, without affecting respiratory burst activation, wortmannin inhibited PMA-stimulated [(18)F]FDG uptake to 66.9+/-1.6% and hexokinase activity to 81.0+/-4.2% (both P<.0005), demonstrating its dependence on PI3K activity. Neither RGD nor wortmannin reversed the other's inhibitory effect on stimulated [(18)F]FDG uptake and hexokinase activity or respiratory burst, which suggests the involvement of distinct signaling pathways., Conclusion: Neutrophil [(18)F]FDG uptake is enhanced by PMA through a mechanism that requires PI3K activity but is independent of integrin receptor occupancy or respiratory burst activation.

High dose [18F]FDG is prepared routinely using an automated synthesizer. Accordingly, an automated dispenser is needed to dispense [18F]FDG at the desired dose while reducing the operator's radiation exposure, and no dispenser capable of vial-to-vial and vial-to-syringe dispensing in one system is commercially available. Here, we describe simple devices for the vial-to-vial and vial-to-syringe dispensing of [18F]FDG.

Unlabelled: The endothelium constitutes a functionally active organ critically involved in angiogenesis. Nitric oxide (NO) is an important regulator of vascular homeostasis and angiogenesis and stimulates glucose metabolism in certain cells. We thus investigated the effect of exogenous NO on (18)F-FDG transport in human endothelial cells., Methods: Human umbilical vein endothelial cells (HUVECs) were treated with the NO donors sodium nitroprusside (SNP) or diethylenetriamine (DETA), in concentrations of 1 micromol/L-1 mmol/L for up to 24 h. (18)F-FDG uptake levels corrected for protein content were determined by cellular radioactivity measured after 30-min incubation. Cells were evaluated for total hexokinase activity and plasma membrane glucose transporter 1 (GLUT1) levels, and involvement of potential signaling pathways was investigated by cotreatment with respective protein kinase inhibitors., Results: Both SNP and DETA stimulated HUVEC (18)F-FDG uptake, which began at 16 h and peaked at 24 h. The increase in (18)F-FDG uptake was dose dependent, reaching 464.0% +/- 49.8% and 254.5% +/- 10.8% of control levels at 24 h with 1 mmol/L SNP and DETA, respectively. Exposure of HUVECs to 1 mmol/L SNP resulted in a 3.5 +/- 0.3-fold elevation in hexokinase activity (P < 0.01) and a significant increase in GLUT1 levels. SNP-stimulated (18)F-FDG uptake was abolished by cotreatment with cycloheximide, the tyrosine kinase inhibitor genistein, the phosphatidylinositol-3 kinase (PI3K) inhibitor wortmannin, or the protein kinase C inhibitor staurosporine., Conclusion: NO stimulates (18)F-FDG uptake in HUVECs through an increase in GLUT1 expression and hexokinase activity, which appears to involve both protein kinase C and PI3K pathways.

Unlabelled: We investigated whether the standardized uptake value (SUV) of the primary tumor, the tumor length measured on a PET image, the number of (18)F-FDG PET-positive nodes, and the PET stage were independent prognostic predictors over other clinical variables in patients with esophageal squamous cell carcinoma who were undergoing curative surgery., Methods: Sixty-nine patients with newly diagnosed esophageal squamous cell carcinoma who underwent preoperative (18)F-FDG PET and curative esophagectomy were included. The events for survival analysis were defined as recurrence or metastasis and cancer-related death. The disease-free and overall survival rates of each variable were estimated by the Kaplan-Meier method. The Cox proportional hazards model was used to evaluate independent prognostic variables for multivariate survival analysis., Results: Using univariate survival analysis, the presence of adjuvant therapy, pathologic stage, number of CT-positive nodes (0, 1, > or =2), tumor length on PET (cutoff: 3 cm, 5 cm), number of PET-positive nodes (0, 1, 2, > or =3), and PET stage (N0 M0, N1 M0, M1) were significant prognostic predictors for disease-free survival. However, only the number of PET-positive nodes was an independent significant prognostic predictor for disease-free survival in multivariate analysis (hazard ratio = 1.87, P < 0.001). In univariate survival analysis, the sex, presence of adjuvant therapy, clinical and pathologic stages, number of CT-positive nodes, maximum SUV of the primary tumor (cutoff: 6.3, 13.7), tumor length on PET, number of PET-positive nodes, and PET stage were significant prognostic predictors for overall survival. In contrast, the clinical stage (hazard ratio = 0.53, P < 0.05), pathologic stage (hazard ratio = 3.14, P < 0.005), tumor length by PET (hazard ratio = 2.74, P = 0.01), and number of PET-positive nodes (hazard ratio = 1.71, P < 0.05) were independent significant prognostic predictors for overall survival in multivariate analysis., Conclusion: In addition to the pathologic stage, (18)F-FDG PET provides noninvasively independent prognostic information using the number of positive lymph nodes and the tumor length on the PET image in preoperative esophageal squamous cell carcinoma. A revised TNM classification system for esophageal carcinoma may consider tumor length and the number of positive lymph nodes as important prognostic factors.

Unlabelled: Activated monocytes with a high (18)F-FDG accumulation can affect the results of clinical PET studies. To better understand the mechanisms regulating monocytic (18)F-FDG uptake, we investigated the effect of priming and respiratory-burst generation and further evaluated the role of potential protein kinase pathways., Methods: Purified human monocytes were primed with interferon-gamma (IFN-gamma), and respiratory burst was generated by stimulation of primed cells with phorbol-12-myristate-13-acetate (PMA). Oxygen-intermediate generation was assessed by luminescence measurements after the addition of lucigenin. (18)F-FDG uptake after 30 min of incubation was measured for unprimed control cells, primed cells, and PMA-stimulated cells. The role of protein kinases was investigated using respective inhibitors., Results: PMA stimulation of primed monocytes dramatically increased oxygen-intermediate generation, leading to a 42.2 +/- 1.1 fold higher level of cumulative luminescence compared with unprimed control cells, whereas IFN-gamma priming alone resulted in low luminescence levels (13.9% +/- 4.6% of PMA-stimulated cells). In contrast, priming alone was sufficient to augment monocytic (18)F-FDG uptake to 273.3% +/- 16.7% of control levels (P < 0.001), and it was not further increased by PMA stimulation. The tyrosine kinase inhibitor, genistein, and the specific protein kinase C inhibitor, staurosporine, completely abolished the priming-induced enhancement of (18)F-FDG uptake and lowered uptake to control levels. Under the same conditions, wortmannin, a phosphatidylinositol 3 kinase (PI3 kinase)-specific inhibitor, and cycloheximide, a protein synthesis inhibitor, were associated with only minor reductions in the enhanced-uptake effect of priming., Conclusion: IFN-gamma priming alone, without stimulation of respiratory-burst activity, is sufficient to induce maximal augmentation of (18)F-FDG uptake in monocytes. Furthermore, this metabolic effect appears to involve tyrosine kinases and the protein kinase C pathway but is independent of the PI3 kinase pathway.

While 18F-FDG labelling of monocytes would allow in vivo trafficking with positron emission tomography (PET), present methods suffer from poor retention of radioactivity. We investigated the feasibility of utilizing insulin for improved [18F]fluorodeoxyglucose (18F-FDG) labelling. Separated human monocytes and lymphocytes were labelled with 18F-FDG with or without 3 h insulin pre-incubation. Insulin had no effect on lymphocyte labelling (21.4+/-0.8% vs 20.8+/-1.1% efficiency, P=NS). However, for monocytes, insulin pre-incubation led to a 169+/-9% increase in labelling efficiency (19.3+/-4.1 vs 32.5+/-1.8, P<0.05), without significant effects on cell activation or viability. Moreover, while only 57.7+/-4.8% and 40.4+/-5.6% of the 18F-FDG was retained at 1 and 3 h for controls, the retention rate increased to 91.6+/-2.1% (P=0.01) and 86.5+/-1.9% (P<0.01) after insulin pre-incubation. Improved 18F-FDG retention was accompanied by a 70.3+/-7.4% decrease in glucose-6-phosphatase activity (P=0.02). PET imaging of rats showing hepatic ischaemia-reperfusion injury demonstrated higher liver uptake for monocytes labelled after insulin treatment. Thus, insulin improves monocytic 18F-FDG uptake and retention, and may provide a feasible labelling method for PET imaging.