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To our knowledge, no prior multicenter clinical trial has reported interobserver agreement of (18)F-FDG PET/CT scans for staging of clinical N0 neck in head and neck cancer. Methods: A total of 287 participants were recruited. For visual analysis, positive nodal uptake of (18)F-FDG was defined as uptake visually greater than activity seen in the blood pool. Results: The negative predictive value of the (18)F-FDG PET/CT for N0 clinical neck was 86% or above for visual assessment (95% CI, 86%–88%) for the 2 central readers and above 90% (95% CI, 90%–95%) for SUV(max) for central reads and site reads dichotomized at the optimal cutoff value of 1.8 and the prespecified cutoff value of 3.5, respectively. The κ coefficients between the 2 expert readers and between central reads and site reads varied between 0.53 and 0.78. Conclusion: The NPV of the (18)F-FDG PET/CT for N0 clinical neck was 86% or above for visual assessment and above 90% for SUV(max) cut points of 1.8 and 3.5 with moderate to substantial agreements.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are 4-repeat tauopathies with overlapping, but also morphologically distinct tau immunoreactive lesions that vary in count by brain region. 18F-flortaucipir positron emission tomography uptake has been reported to correlate with overall tau burden, and in one CBD case to have greater affinity to threads than tangles. We determine whether 18F-flortaucipir uptake is associated with histologic lesion type in 4-repeat tauopathies. Methods: We performed semi-quantitative regional lesion counts on pretangles/neurofibrillary tangles, threads, oligodendroglial coiled bodies, tufted astrocytes, and astrocytic plaques in 29 autopsied 4-repeat tauopathies (PSP = 16; CBD=13). Regression models were used for statistical analyses. Results:18F-flortaucipir uptake marginally correlated with threads in the precentral cortex (P = 0.04) and with astrocytic lesions in the red nucleus (P = 0.05). Conclusion: The findings do not support 18F-flortaucipir having differential affinity to any 4-repeat tau lesion type.

Amyloid-β (Aβ) deposition as seen on PET using an Aβ-binding agent is a critical diagnostic biomarker for Alzheimer disease (AD). Some reports suggest using white matter (WM) as a reference region for quantification of serial Aβ PET studies; however, nonspecific WM retention in Aβ PET in people with dementia or cognitively unimpaired (CU) has been widely reported and is poorly understood. Methods: To investigate the suitability of WM as a reference region and the factors affecting WM 11C-Pittsburgh compound B (11C-PiB) uptake variability, we conducted a retrospective study on 2 large datasets: a longitudinal study of participants (n = 577) who were CU, had mild cognitive impairment, or had dementia likely due to AD; and a cross-sectional study of single-scan PET imaging in CU subjects (n = 1,349). In the longitudinal study, annual changes in WM 11C-PiB uptake were assessed, and in the cross-sectional study, WM 11C-PiB uptake was assessed relative to subject age. Results: Overall, we found that WM 11C-PiB uptake showed age-related increases, which varied with the WM regions selected. Further, variable annual WM 11C-PiB uptake changes were seen with different gray matter (GM) 11C-PiB baseline uptake levels. Conclusion: WM binding increases with age and varies with GM 11C-PiB. These correlations should be considered when using WM for normalization in 11C-PiB PET studies. The cerebellar crus1+crus2 showed no increase with age and cerebellar GM+WM showed minimal increase, supporting their use as reference regions for cross-sectional studies comparing wide age spans. In longitudinal studies, the increase in WM uptake may be minimal in the short-term and thus using WM as a reference region in these studies seems reasonable. However, as participants age, the findings may be affected by changes in WM uptake. Changes in WM 11C-PiB uptake may relate to disease progression, warranting examination of the causes of WM 11C-PiB uptake.

Abnormalities of zinc homeostasis are indicated in many human diseases. A noninvasive imaging method for monitoring zinc in the body would be useful to understand zinc dynamics in health and disease. To provide a PET imaging agent for zinc, we have investigated production of (63)Zn (half-life, 38.5 min) via the (63)Cu(p,n)(63)Zn reaction using isotopically enriched solutions of (63)Cu-copper nitrate. A solution target was used for rapid isolation of the (63)Zn radioisotope from the parent (63)Cu ions. Initial biologic evaluation was performed by biodistribution and PET imaging in normal mice.To produce (63)Zn, solutions of (63)Cu-copper nitrate in dilute nitric acid were irradiated by 14-MeV protons in a low-energy cyclotron. An automated module was used to purify (63)Zn from (63)Cu in the target solution. The (63)Cu-(63)Zn mixture was trapped on a cation-exchange resin and rinsed with water, and the (63)Zn was eluted using 0.05 N HCl in 90% acetone. The resulting solution was neutralized with NaHCO3, and the (63)Zn was then trapped on a carboxymethyl cartridge, washed with water, and eluted with isotonic 4% sodium citrate. Standard quality control tests were performed on the product according to current good manufacturing practice, including radionuclidic identity and purity, and measurement of nonradioactive Zn(+2), Cu(+2), Fe(+3), and Ni(+2) by ion-chromatography high-performance liquid chromatography. Biodistribution and PET imaging studies were performed in B6.SJL mice after intravenous administration of (63)Zn-zinc citrate. (63)Cu target material was recycled by eluting the initial resin with 4N HNO3.Yields of 1.07 ± 0.22 GBq (uncorrected at 30-36 min after end of bombardment) of (63)Zn-zinc citrate were obtained with a 1.23 M (63)Cu-copper nitrate solution. Radionuclidic purity was greater than 99.9%, with copper content lower than 3 μg/batch. Specific activities were 41.2 ± 18.1 MBq/μg (uncorrected) for the (63)Zn product. PET and biodistribution studies in mice at 60 min showed expected high uptake in the pancreas (standard uptake value, 8.8 ± 3.2), liver (6.0 ± 1.9), upper intestine (4.7 ± 2.1), and kidney (4.2 ± 1.3).A practical and current good manufacturing practice-compliant preparation of radionuclidically pure (63)Zn-zinc citrate has been developed that will enable PET imaging studies in animal and human studies. (63)Zn-zinc citrate showed the expected biodistribution in mice.

Dysfunctional insulin signaling may affect brain metabolism or amyloid deposition. We investigated the associations of type 2 diabetes with amyloid accumulation measured using (11)C-Pittsburgh compound B ((11)C-PiB) and brain hypometabolism measured using (18)F-FDG PET.We studied a sample of nondemented participants from the population-based Mayo Clinic Study of Aging. All subjects underwent MR imaging, amyloid PET, and (18)F-FDG PET. Alzheimer disease (AD) signature and region-of-interest (ROI) measures for (11)C-PiB retention ratio and (18)F-FDG ratio were measured. Diabetes was assessed from the Rochester Epidemiology Project medical records linkage system.Among 749 participants (median age, 79.0 y; 56.5% men, 81.0% cognitively normal; 20.6% diabetic individuals), (18)F-FDG hypometabolism ((18)F-FDG ratio1.31) in the AD signature meta-ROI was more common in diabetic individuals (48.1%) than in nondiabetic individuals (28.9%; P0.001). The median (18)F-FDG ratio was lower in diabetic individuals than in nondiabetic individuals in the AD signature meta-ROI (1.32 vs. 1.40, P0.001) and in the angular (1.40 vs. 1.48, P0.001) and posterior cingulate gyri ROIs (1.63 vs. 1.72, P0.001). The odds ratio (OR) for abnormal AD signature (18)F-FDG hypometabolism was elevated (2.28; 95% confidence interval [CI], 1.56-3.33) in diabetic individuals versus nondiabetic individuals after adjustment for age, sex, and education and after additional adjustment for apolipoprotein ε4 allele, glycemic level, and cognitive status (OR, 1.69; 95% CI, 1.10-2.60). However, the AD signature (11)C-PiB retention ratio was similar in diabetic individuals versus nondiabetic individuals (OR, 1.03; 95% CI, 0.71-1.51; P = 0.87). In post hoc analyses in nondiabetic individuals, a 1% increase in hemoglobin A1c was associated with greater AD signature hypometabolism in cognitively normal subjects (OR, 1.93; 95% CI, 1.03-3.62; P = 0.04) and in the total cohort (OR 1.59; 95% CI, 0.92-2.75; P = 0.10).Diabetes and poor glycemic control in nondiabetic individuals may enhance glucose hypometabolism in AD signature regions. These factors should be investigated in longitudinal studies for their role in detecting onset of symptoms in AD.

Oncologic 18F-FDG PET/CT is rapidly gaining acceptance in clinical practice. However, the referring physician’s attitude toward the usefulness of this diagnostic modality is unknown. This survey was undertaken to collect information regarding the current perspective of referring physicians on oncologic PET/CT. Methods: We conducted a prospective worldwide, Web-based survey of physicians who manage cancer patients. A total of 963 referring physicians completed a 20-question survey focused on their experience with oncologic 18F-FDG PET/CT. Attention was directed toward their confidence about indications, their satisfaction with related educational resources, the quality of interaction with interpreting physicians, and practical problems encountered. The respondents included oncologists (38.5%, n = 371), hematologists (16.4%, n = 158), radiation oncologists (9.0%, n = 87), surgeons (30.3%, n = 292), and other physicians (5.7%, n = 55). Results: Only 25.2% of respondents considered the oncologic 18F-FDG PET/CT indications to be well established and defined. Frequent uncertainty about the need for a PET scan was indicated by 62.3% of the respondents. High cost and overinterpretation of findings were the most commonly reported concerns (47.0% and 40.9%, respectively). The experience and skill level of the interpreting physician was considered very important by 96.8% of the surveyed physicians. Conclusion: Referring physicians expressed considerable uncertainty about the appropriate use of oncologic PET/CT. Additional major concerns are procedure costs and quality of interpretation. The responses suggest a strong need for efforts to educate referring and interpreting physicians about the appropriate use of 18F-FDG PET/CT in oncology.