BACKGROUND:Adrenal tumours are frequently detected by conventional imaging. However, computed tomography and magnet resonance imaging have limited specificity in classifying the most prevalent tumour type, adrenocortical adenoma (ACA), which typically does not require surgery. We proposed that combined molecular imaging with [18F]Fluorodeoxyglucose-positron emission tomography (FDG PET) and [123I]Iodometomidate-single photon emission tomography (IMTO SPECT) improves non-invasive classification of ACA. METHODS:This cross-sectional, multicentre diagnostic study included patients (≥30 years) with non-functioning indeterminate adrenal masses (>3 cm or increase >1 cm, Hounsfield units [HU] ≥10 on unenhanced computed tomography [CT]) scheduled for surgery. Using histopathology as the reference, we assessed the accuracy of FDG/IMTO imaging as an ACA-test, assuming that low FDG with high IMTO uptake is indicative of ACA, with a focus on high specificity and moderate to high sensitivity. We also investigated its accuracy in detecting or excluding adrenocortical carcinoma (ACC) and evaluated FDG and unenhanced CT in assessing malignancy. TRIAL-REGISTRATION:EudraCT 2012-003604-13; ClinicalTrials.gov-identifier NCT02010957. FINDINGS:From July 2015 to December 2020, 85 patients were enrolled, with 77 included in the final analysis (53 benign, 30 ACA, 9 ACC). FDG/IMTO-imaging classified ACA with high specificity (95·7% [95% CI 85·2%-99·47%]), high positive predictive value (87·5% [95% CI 61·7%-98·4%]) and high positive likelihood ratio (11·1 [95% CI 3·2-122]). However, sensitivity was low (48·3% [95% CI 29·4%-67·5%]) due to moderate/high FDG uptake in 14 of 30 ACA. Malignant masses were classified with high sensitivity but low-to-moderate specificity by both unenhanced CT (cut-off HU ≥20 sensitivity 100% [95% CI 85·8%-100%], specificity 26·4% [95% CI 15·3%-40·3%]) and FDG (visual analysis sensitivity 95·8% [95% CI 78·9%-99·9%], specificity 62·3% [95% CI 47·9%-75·2%]). All four study-related AEs were grade 1, the seven serious AEs were not study-related. INTERPRETATION:Combined FDG/IMTO-imaging classifies ACA with high specificity, potentially reducing unnecessary surgery. A sub-group of FDG-positive ACA lowers sensitivity. FUNDING:German Research Foundation and EU-FP7.

![Figure][1] Diane M. Simeone, MD Ken Herrmann, MD, from the Universitätsklinikum Essen, and Johannes Czernin, MD, from the David Geffen School of Medicine at the University of California Los Angeles, talked with Diane M. Simeone, MD, about her career advancing clinical research in

The use of Isolated lung perfusion (ILP), combined with medical imaging modalities such as positron emission tomography-computed tomography (PET/CT), provides real-time visualization of tumors in ventilated and perfused vital lung tissue. This experiment intends to show the feasibility and benefits of using ILP combined with PET/CT imaging. Following lung surgery on a 49-year-old male, his left lower lobectomy specimen, which held a typical carcinoid tumor, was preserved on normothermic ILP. Gallium-68-Edotreotide ([68Ga]-DOTATOC) was administered into the ILP circuit, and dynamic emission data from PET/CT was acquired. ILP was carried out for 120 minutes. Near physiologic gas exchange and glucose metabolism were preserved throughout the experiment. The time activity curves (TAC) of 5 different volumes of interest (VOI) showed notable differences in tracer uptake over time. The peripheral area of the carcinoid exhibited delayed but high somatostatin receptor agonist uptake compared to the surrounding parenchyma and the intrapulmonary artery. However, the central area of the carcinoid showed very low [68Ga]-DOTATOC uptake. This experiment demonstrates the potential of ILP combined with PET/CT for kinetic modeling in experimental nuclear medicine imaging. By providing visualization of tracer uptake in perfused lung tissue, this model could potentially improve our understanding of tumor physiology and molecular imaging.

Supplementary Data from Protein Expression Profiling in Esophageal Adenocarcinoma Patients Indicates Association of Heat-Shock Protein 27 Expression and Chemotherapy Response

The randomized PETAL trial failed to demonstrate a benefit of interim FDG-PET (iPET)-based treatment intensification over continued standard therapy with CHOP (plus rituximab (R) in CD20-positive lymphomas). We hypothesized that PET analysis of all lymphoma manifestations may identify patients who benefitted from treatment intensification. A previously developed neural network was employed for iPET analysis to identify the highest pathological FDG uptake (max-SUV AI ) and the mean FDG uptake of all lymphoma manifestations (mean-SUV AI ). High mean-SUV AI uptake was determined separately for iPET-positive and iPET-negative patients. The endpoint was time-to-progression (TTP). There was a significant interaction of additional rituximab and mean-SUV AI in the iPET-negative group (HR = 0.6, p < 0.05). Patients with high mean-SUV AI had significantly prolonged TTP when treated with 6xR-CHOP + 2 R (not reached versus 52 months, p < 0.05), whereas max-SUV manual failed to show an impact of additional rituximab. In the iPET-positive group, patients with high mean-SUV AI had a significantly longer TTP with (R-)CHOP than with the Burkitt protocol (14 versus 4 months, p < 0.01). Comprehensive iPET evaluation may provide new prognosticators in aggressive lymphoma. Additional application of rituximab was associated with prolonged TTP in iPET-negative patients with high mean-SUV AI . Comprehensive iPET interpretation could identify high-risk patients who benefit from study-specific interventions.

Irfan Vardarli Christoph Rischpler 3 Ken Herrmann Frank Weidemann 1Department of Medicine I, Klinikum Vest, Knappschaftskrankenhaus Recklinghausen, Academic Teaching Hospital, Ruhr-University Bochum, Recklinghausen, Germany; 2HerzUnd Gefäßzentrum Klinikum Vest, Recklinghausen, Germany; 3Department of Nuclear Medicine, University Hospital Essen, Essen, Germany Abstract: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by absence or deficient activity of α-galactosidase A (α-Gal A) due to mutations in the α-galactosidase A gene (GLA), leading to progressive accumulation of globotriaosylceramide (Gb3) in tissues and organs including heart, kidney, the eyes, vascular endothelium, the nervous system and the skin. Cardiac involvement is leading to fatal complications and reduced life expectancy. FD is treatable with disease-specific treatment (enzyme replacement therapy (ERT) or with chaperone therapy). Therefore, the early diagnosis of FD is crucial for reducing the morbidity and mortality. Screening of high-risk populations (eg, patients with unexplained left ventricular hypertrophy (LVH), young patients with unexplained stroke, and patients with unexplained renal failure proteinuria or microalbuminuria) yields good results. The diagnostic algorithm is gender-specific. Initially, the measurement of α-Gal A activity is recommended in males, and optionally in females. In males with non-diagnostic residual activity (5–10%) activity, genetic testing is afterwards done for confirming the diagnosis. In fact, diagnosis of FD is not possible without genetic testing for both males and females. Globotriaosysphingosine (lyso-Gb3) for identification of atypical FD variants and highsensitive troponin T (hsTNT) for identification of cardiac involvement are also important diagnostic biomarkers. The aim of this review was to provide an update on diagnosis and screening of patients with FD.

OBJECTIVE:To investigate the association between levodopa-induced dyskinesias and striatal cholinergic activity in patients with Parkinson's disease.METHODS:This study included 13 Parkinson's disease patients with peak-of-dose levodopa-induced dyskinesias, 12 nondyskinetic patients, and 12 healthy controls. Participants underwent 5-[123I]iodo-3-[2(S)-2-azetidinylmethoxy]pyridine single-photon emission computed tomography, a marker of nicotinic acetylcholine receptors, [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography, to measure dopamine reuptake transporter density and 2-[18F]fluoro-2-deoxyglucose positron emission tomography to assess regional cerebral metabolic activity. Striatal binding potentials, uptake values at basal ganglia structures, and correlations with clinical variables were analyzed.RESULTS:Density of nicotinic acetylcholine receptors in the caudate nucleus of dyskinetic subjects was similar to that of healthy controls and significantly higher to that of nondyskinetic patients, in particular, contralaterally to the clinically most affected side.INTERPRETATION:Our findings support the hypothesis that the expression of dyskinesia may be related to cholinergic neuronal excitability in a dopaminergic-depleted striatum. Cholinergic signaling would play a role in maintaining striatal dopaminergic responsiveness, possibly defining disease phenotype and progression.

We evaluated the observer agreement for 68Ga-DOTATATE PET/CT study interpretations in patients with neuroendocrine tumors (NET). Methods: 68Ga-DOTATATE PET/CT was performed in 50 patients with known or suspected NET of the small bowel (n = 19), pancreas (n = 14), lung (n = 4) or other location (n = 13). Images were reviewed by seven observers who used a standardized approach for image interpretation. Observers were classified as having low (<500 scans or <5 years experience with 68Ga-DOTATATE PET/CT; n = 4) or high level of experience (≥500 scans and ≥5 years experience with 68Ga-DOTATATE PET/CT; n = 3). Interpretation by the primary nuclear medicine physician un-blinded to all clinical and imaging data served as reference standard. Interobserver agreement was determined by Cohen's κ and intraclass correlation coefficient (ICC) with corresponding 95% confidence interval (CI). Results: Interobserver agreement was substantial and the median number of false findings (FF) was low for the overall scan result; i.e. positive versus negative study (κ = 0.80, 95%CI 0.74-0.86; FF = 3), organ involvement (κ = 0.70, 95%CI 0.64-0.76; FF = 5), and lymph node involvement (κ = 0.71, 95%CI 0.65-0.78; FF = 6). The interobserver agreement was substantial to almost-perfect and the average absolute difference (Δ) to the reference reader was low for number of organ and lymph node metastases (ICC = 0.84, 95%CI 0.77-0.89, Δ = 0.45 and ICC = 0.77, 95%CI 0.69-0.84, Δ = 0.45), tumor SUVmax (ICC = 0.99, 95%CI 0.97-0.99; Δ = 0.44) and reference SUV (SUVmean spleen: ICC = 0.81, Δ = 1.10; SUVmax liver ICC = 0.79, Δ = 0.62). Interpretations of the appropriateness for peptide-receptor radionuclide therapy (PRRT) varied more significantly among observers (κ = 0.64, 95%CI 0.57-0.70) and a higher frequency of false positive recommendations for PRRT occurred in observers with low versus high levels of experience (range, 7-12 versus 4-8). Conclusion: The interpretation of 68Ga-DOTATATE PET/CT for NET staging is consistent among readers with low and high levels of experience. However, image based recommendations for or against PRRT require experience and training. by on October 1, 2017. For personal use only. jnm.snmjournals.org Downloaded from

withdrawn.

Somatostatin receptor imaging with Ga-68-DOTATATE PET/CT (DOTATATE) is increasingly used for managing patients with neuroendocrine tumors. The objective of this study was to determine referring physicians' perspectives on the impact of DOTATATE on the management of neuroendocrine tumors. Methods: A set of 2 questionnaires (pre-PET and post-PET) was sent to the referring physicians of 100 consecutive patients with known or suspected neuroendocrine tumors, who were evaluated with DOTATATE. Questionnaires on 88 patients were returned (response rate, 88%). Referring physicians categorized the DOTATATE findings on the basis of the written PET reports as negative, positive, or equivocal for disease. The likelihood for metastatic disease was scored as low, moderate, or high. The intended management before and changes as a consequence of the PET study were indicated. Results: The indications for PET/CT were initial and subsequent treatment strategy assessments in 14% and 86% of patients, respectively. Referring physicians reported that DOTATATE led to a change in suspicion for metastatic disease in 21 patients (24%; increased and decreased suspicion in 9 [10%] and 12 [14%] patients, respectively). Intended management changes were reported in 53 of 88 (60%) patients. Twenty patients (23%) scheduled to undergo chemotherapy were switched to treatments without chemotherapy, and 6 (7%) were switched from watch-and-wait to other treatment strategies. Conversely, 5 patients (6%) were switched from their initial treatment strategy to watch-and-wait. Conclusion: This survey of referring physicians demonstrates a substantial impact of DOTATATE on the intended management of patients with neuroendocrine tumors.

1474 Objectives: CET, a chimeric monoclonal antibody directed against epidermal growth factor receptor (EGFR) has proved therapeutic activity in SCC in-vitro and in-vivo by enhancing the activity of both chemo- and radiotherapy. Aim was to investigate the early influence of CET on tumor glucose metabolism. Methods: Patients with locally advanced esophageal SCC received single agent CET for two weeks (400mg/m2 i. v. d -15 followed by 250mg/m2 d -8) before entering neoadjuvant chemoradiation (CRT): radiotherapy (45Gy cumulative dose; 1.8Gy/d), CET (250mg/m2) plus oxaliplatin and 5-FU cont. i.v. (doses according to dose escalation protocol). Surgery was scheduled 4-6 weeks after completion of CRT. Tumor FDG uptake was assessed by PET at baseline, two weeks after start of CET and two weeks after start of CRT. Tumor biopsies were taken before and two weeks after the start of CET. Results: 5 of 6 patients are assessable for early metabolic changes. Decreases in the standard uptake value two weeks after the start of CET ranged from -7% to -44% for the for the early and from -17% to -51% for the later time point, respectively. So far, two patients underwent surgery (R0 resection both) and both were classified as histopathological responders. Immunohistochemical analyses (kinases involved in EGFR-dependent signal transduction, proteins representing proliferation and apoptosis) are under way. Conclusions: This pilot study shows that the single agent CET has a clear and early repressive effect on tumor glucose uptake.

In view of the commercial success of integrated PET/CT scanners, there is an increasing interest in comparable SPECT/CT systems. SPECT in combination with CT enables a direct correlation of anatomic information and functional information, resulting in better localization and definition of scintigraphic findings. Besides anatomic referencing, the added value of CT coregistration is based on the attenuation correction capabilities of CT. The number of clinical studies is limited, but pilot studies have indicated a higher specificity and a significant reduction in indeterminate findings. The superiority of SPECT/CT over planar imaging or SPECT has been demonstrated in bone scintigraphy, somatostatin receptor scintigraphy, parathyroid scintigraphy, and adrenal gland scintigraphy. Also, rates of detection of sentinel nodes by biopsy can be increased with SPECT/CT. This review highlights recent technical developments in integrated SPECT/CT systems and summarizes the current literature on potential clinical uses and future directions for SPECT/CT in cardiac, neurologic, and oncologic applications.

Introduction: To evaluate [C-11]Choline positron emission tomography (PET/computed tomography (CT) for staging and restaging of patients with advanced prostate cancer and to compare the diagnostic performance of PET, CT and PET/CT.Methods: Forth-five consecutive patients with advanced prostate cancer underwent [C-11]Choline-PET/CT between 5/2007 and 2/2006.Results: Overall. 295 lesions were detected: PET alone, 178 lesions; diagnostic CT, 22 1 lesions; PET/CT (low-close CT), 272 lesions; PET/ CT (diagnostic CT). 295 lesions. Two thirds of the lesions, were located ill the bone: one third ill the prostate. lymph nodes, periprostatic tissue and soft tissue (lung, liver). The use of diagnostic CT did not result ill a statistically significant difference with respect to lesion The use of diagnostic localization certainly and lesion characterization (P=.063, P=.063), PET-negative bill PET/CT-positive lesions were mostly localized in the bone (78%, 91/117) as were PET-positive and CT-negative lesions (72%, 53/74). Of the latter, 91% (48/53) represented bone marrow and 9% (5/53) cortical involvement,Conclusions: Staging and restaging with [C-11]Choline PET/CT in patients with advanced prostate cancer improve the assessment of local and regional recurrent as well as metastatic disease including skeletal manifestations. [C-11]Choline PET/CT (with a low-dose CT) results in improved localiziation and lesion characterization. [C-11]Choline PET/CT provides ill added value for skeletal manifestations. [C-11]Choline PET/CT changed disease management in 11 (24%) of 45 patients with advanced Prostate cancer. (C) 2008 Elsevier Inc. All rights reserved.