Beschreibung: Off-target binding in the basal ganglia is commonly observed in the 18 F-AV-1451 PET studies of the elderly. We sought to investigate the relationship between this phenomenon in the basal ganglia and iron accumulation using iron-sensitive R 2 * MRI. Methods: Fifty-nine healthy controls and 61 patients with Alzheimer disease and mild cognitive impairment underwent 18 F-AV-1451 PET and R 2 * MRI studies. A correlation analysis was performed for age, 18 F-AV-1451 binding, and R 2 * values. Results: There was an age-related increase in both 18 F-AV-1451 binding in the basal ganglia and R 2 * values in the putamen in both the controls and the Alzheimer disease/mild cognitive impairment patients. 18 F-AV-1451 binding in the basal ganglia increased with R 2 * values. Conclusion: Off-target 18 F-AV-1451 binding in the basal ganglia is associated with the age-related increases in iron accumulation. Postmortem studies are required to further investigate the nature of this association.

Beschreibung: Assessing therapy response of breast cancer bone metastases is challenging. In retrospective studies, serial 18 F-FDG PET was predictive of time to skeletal-related events (tSRE) and time to progression (TTP). 18 F-NaF PET improves bone metastasis detection compared with bone scanning. We prospectively tested 18 F-FDG PET and 18 F-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (MBC). Methods: Patients with bone-dominant MBC were imaged with 18 F-FDG PET and 18 F-NaF PET before starting new therapy (scan1) and again at a range of times centered around approximately 4 mo later (scan2). Maximum standardized uptake value (SUV max ) and lean body mass adjusted standardized uptake (SUL peak ) were recorded for a single index lesion and up to 5 most dominant lesions for each scan. tSRE, TTP, and OS were assessed exclusive of the PET images. Univariate Cox regression was performed to test the association between clinical endpoints and 18 F-FDG PET and 18 F-NaF PET measures. mPERCIST (Modified PET Response Criteria in Solid Tumors) were also applied. Survival curves for mPERCIST compared response categories of complete response+partial response+stable disease versus progressive disease for tSRE, TTP, and OS. Results: Twenty-eight patients were evaluated. Higher 18 F-FDG SUL peak at scan2 predicted shorter time to tSRE ( P = 〈0.001) and TTP ( P = 0.044). Higher 18 F-FDG SUV max at scan2 predicted a shorter time to tSRE ( P = 〈0.001). A multivariable model using 18 F-FDG SUV max of the index lesion at scan1 plus the difference in SUV max of up to 5 lesions between scans was predictive for tSRE and TTP. Among 24 patients evaluable by 18 F-FDG PET mPERCIST, tSRE and TTP were longer in responders (complete response, partial response, or stable disease) than in nonresponders (progressive disease) ( P = 0.007, 0.028, respectively), with a trend toward improved survival ( P = 0.1). An increase in the uptake between scans of up to 5 lesions by 18 F-NaF PET was associated with longer OS ( P = 0.027). Conclusion: Changes in 18 F-FDG PET parameters during therapy are predictive of tSRE and TTP, but not OS. mPERCIST evaluation in bone lesions may be useful in assessing response to therapy and is worthy of evaluation in multicenter, prospective trials. Serial 18 F-NaF PET was associated with OS but was not useful for predicting TTP or tSRE in bone-dominant MBC.

Beschreibung: 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-[(2 R )-2-[[(2 R )-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.

Beschreibung: We evaluated how troglitazone influences cancer cell glucose metabolism and uptake of 18 F-FDG, and we investigated its molecular mechanism and relation to the drug’s anticancer effect. Methods: Human T47D breast and HCT116 colon cancer cells that had been treated with troglitazone were measured for 18 F-FDG uptake, lactate release, oxygen consumption rate, mitochondrial membrane potential, and intracellular reactive oxygen species. Viable cell content was measured by sulforhodamine-B assays. Results: Treatment with 20 μM troglitazone for 1 h acutely increased 18 F-FDG uptake in multiple breast cancer cell lines, whereas HCT116 cells showed a delayed reaction. In T47D cells, the response occurred in a dose-dependent (threefold increase by 40 μM) manner independent of peroxisome proliferator-activated receptor- and was accompanied by a twofold increase of lactate production, consistent with enhanced glycolytic flux. Troglitazone-treated cells showed severe reductions of the oxygen consumption rate, indicating suppression of mitochondrial respiration, which was accompanied by significantly decreased mitochondrial membrane potential and increased concentration of reactive oxygen species. Troglitazone dose-dependently reduced T47D and HCT116 cell content, which was significantly potentiated by restriction of glucose availability. In T47D cells, cell reduction closely correlated with the magnitude of increase in relative 18 F-FDG uptake ( r = 0.821, P = 0.001). Conclusion: Troglitazone stimulates cancer cell uptake of 18 F-FDG through a shift of metabolism toward glycolytic flux, likely as an adaptive response to impaired mitochondrial oxidative respiration.