Repeatability of brown adipose tissue measurements on FDG PET/CT following a simple cooling procedure for BAT activation.

Brown Adipose Tissue (BAT) is present in a significant number of adult humans and can be activated by exposure to cold. Measurement of active BAT presence, activity, and volume are desirable for determining the efficacy of potential treatments intended to activate BAT. The repeatability of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements of BAT presence, activity, and volume under controlled conditions has not been extensively studied. Eleven female volunteers underwent double baseline FDG PET imaging performed following a simple, regional cold intervention intended to activate brown fat. The cold intervention involved the lightly-clothed participants intermittently placing their feet on a block of ice while sitting in a cooled room. A repeat study was performed under the same conditions within a target of two weeks. FDG scans were obtained and maximum standardized uptake value adjusted for lean body mass (SULmax), CT Hounsfield units (HU), BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were determined according to the Brown Adipose Reporting Criteria in Imaging STudies (BARCIST) 1.0. A Lin's concordance correlation (CCC) of 0.80 was found for BMV between test and retest imaging. Intersession BAT SULmax was significantly correlated (r = 0.54; p < 0.05). The session #1 mean SULmax of 4.92 ± 4.49 g/mL was not significantly different from that of session #2 with a mean SULmax of 7.19 ± 7.34 g/mL (p = 0.16). BAT SULmax was highly correlated with BMV in test and retest studies (r ≥ 0.96, p < 0.001). Using a simplified ice-block cooling method, BAT was activated in the majority (9/11) of a group of young, lean female participants. Quantitative assessments of BAT SUL and BMV were not substantially different between test and retest imaging, but individual BMV could vary considerably. Intrasession BMV and SULmax were strongly correlated. The variability in estimates of BAT activity and volume on test-retest with FDG should inform sample size choice in studies quantifying BAT physiology and support the dynamic metabolic characteristics of this tissue. A more sophisticated cooling method potentially may reduce variations in test-retest BAT studies.

Measurement of Brown Adipose Tissue Activity Using Microwave Radiometry and 18F-FDG PET/CT.

The aim of this study was to evaluate the operating characteristics of a microwave radiometry system in the noninvasive assessment of activated and nonactivated brown adipose tissue (BAT) and normal-tissue temperatures, reflecting metabolic activity in healthy human subjects. The radiometry data were compared with 18F-FDG PET/CT images in the same subjects. Methods: Microwave radiometry and 18F-FDG PET/CT were sequentially performed on 19 participants who underwent a cold intervention to maximize BAT activation. The cold intervention involved the participants' intermittently placing their feet on an ice block while sitting in a cool room. Participants exhibiting BAT activity qualitatively on PET/CT were scanned again with both modalities after undergoing a BAT minimization protocol (exposure to a warm room and a 20-mg dose of propranolol). Radiometry was performed every 5 min for 2 h before PET/CT imaging during both the warm and the cold interventions. A grid of 15-20 points was drawn on the participant's upper body (data were collected at each point), and a photograph was taken for comparison with PET/CT images. Results: PET/CT identified increased signal consistent with BAT activity in 11 of 19 participants. In 10 of 11 participants with active BAT, radiometry measurements collected during the cold study were modestly, but significantly, higher on points located over areas of active BAT on PET/CT than on points not exhibiting BAT activity (P < 0.01). This difference lessened during the warm studies: 7 of 11 participants showed radiometry measurements that did not differ significantly between the same set of points. The mean radiometry result collected during BAT maximization was 33.2°C ± 1.5°C at points designated as active and 32.7°C ± 1.3°C at points designated as inactive (P < 0.01). Conclusion: Passive microwave radiometry was shown to be feasible and, with substantial improvements, has the potential to noninvasively detect active brown adipose tissue without a radiotracer injection.

A comparison of FLT to FDG PET/CT in the early assessment of chemotherapy response in stages IB-IIIA resectable NSCLC.

BACKGROUND: The aim of this study was to compare the percentage change in 18F-fluorothymidine (FLT) standard uptake value (SUV) between baseline and after one cycle of chemotherapy in patients categorized by RECIST 1.1 computed tomography (CT) as responders or non-responders after two cycles of therapy. Change in 18F-fluorodeoxyglucose (FDG) uptake was also compared between these time points. Nine patients with newly diagnosed, operable, non-small cell lung cancer (NSCLC) were imaged with FDG positron emission tomography/CT (PET), FLT PET/CT, and CT at baseline, following one cycle of neoadjuvant therapy (75 mg/m2 docetaxel + 75 mg/m2 cisplatin), and again after the second cycle of therapy. All patients had a biopsy prior to enrollment and underwent surgical resection within 4 weeks of post-cycle 2 imaging. RESULTS: Between baseline and post-cycle 1, non-responders had mean SULmax (maximum standard uptake value adjusted for lean body mass) increases of 7.0 and 3.4% for FDG and FLT, respectively. Responders had mean decreases of 44.8 and 32.0% in FDG and FLT SULmax, respectively, between baseline and post-cycle 1 imaging. On post-cycle 1 imaging, primary tumor FDG SUL values were significantly lower in responders than in non-responders (P = 0.016). Primary tumor FLT SUL values did not differ significantly between these groups. Using the change from baseline to post-cycle 1, receiver-operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.94 for FDG and 0.78 for FLT in predicting anatomic tumor response after the second cycle of therapy. CONCLUSIONS: Fractional decrease in FDG SULmax from baseline to post-cycle 1 imaging was significantly different between anatomic responders and non-responders, while percentage changes in FLT SULmax were not significantly different between these groups over the same period of time.

Assessment of Imaging Modalities and Response Metrics in Ewing Sarcoma: Correlation With Survival.

PURPOSE: Despite the rapidly increasing use of [18F]fluorodeoxyglucose (FDG) -positron emission tomography (PET), the comparison of anatomic and functional imaging in the assessment of clinical outcomes has been lacking. In addition, there has not been a rigorous evaluation of how common radiologic criteria or the location of the radiology reader (local v central) compare in the ability to predict benefit. In this study, we aimed to compare the effectiveness of various radiologic response assessments for the prediction of overall survival (OS) within the same data set of patients with sarcoma. METHODS: We analyzed assessments made during a clinical trial of a novel IGF1R antibody in Ewing sarcoma: PET Response Criteria in Solid Tumors (PERCIST) for functional imaging and WHO criteria (performed locally and centrally), RECIST, and volumetric analysis for anatomic imaging. We compared the effectiveness of the various criteria for the prediction of progression and survival. RESULTS: For volume analysis, progression-defined as cumulative lesion volume increase of 100% at 6 weeks-was the optimal cutoff for decreased OS (P < .001). Assessment of the day-9 FDG-PET scan was associated with reduced OS in progressors compared with nonprogressors (P = .001) and with improved OS in responders compared with nonresponders. Significant variations in response (18% to 44%) and progression (9% to 50%) were observed between the different criteria. The comparison of central and local interpretation of anatomic imaging produced similar outcomes. PET was superior to anatomic imaging in identification of a response. Volume analysis identified the most responders among the anatomic imaging criteria. CONCLUSION: An early signal with FDG-PET on day 9 and volume analysis were the best predictors of benefit. Validation of the volumetric analysis is required.

TBCRC 008: early change in 18F-FDG uptake on PET predicts response to preoperative systemic therapy in human epidermal growth factor receptor 2-negative primary operable breast cancer.

UNLABELLED: Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemotherapy and enhance outcomes. We conducted a multicenter randomized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SUL(max)) on (18)F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes. METHODS: Participants were randomly assigned to 12 wk of preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m(2) weekly) with vorinostat (400 mg orally daily, days 1-3 of every 7-d period) or placebo. All patients underwent (18)F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SUL(max) on (18)F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR. RESULTS: In an intent-to-treat analysis (n = 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n = 59), we observed a significant difference in median change in SUL(max) 15 d after initiating preoperative therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P = 0.003). Patients with 50% or greater reduction in SUL(max) were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3-22.7; P = 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not. CONCLUSION: Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SUL(max) on (18)F-FDG PET 15 d after the initiation of preoperative therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test (18)F-FDG PET as a potential treatment-selection biomarker.