4Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MinnesotaOur aims were (1) by computed tomography (CT) to establish a population database for pancreas volume (parenchyma and fat) from birth to age 100 years, (2) in adults, to establish the impact of gender, obesity, and the presence or absence of type-2 diabetes on pancreatic volume (parenchyma and fat), and (3) to confirm the latter histologically from pancreatic tissue obtained at autopsy with a particular emphasis on whether pancreatic fat is increased in type-2 diabetes. We measured pancreas volume in 135 children and 1,886 adults (1,721 nondiabetic and 165 with type-2 diabetes) with no history of pancreas disease who had undergone abdominal CT scan between 2003 and 2006. Pancreas volume was computed from the contour of the pancreas on each CT image. In addition to total pancreas volume, parenchymal volume, fat volume, and fat/parenchyma ratio (F/P ratio) were determined by CT density. We also quantified pancreatic fat in autopsy tissue of 47 adults (24 nondiabetic and 23 with type-2 diabetes). During childhood and adolescence, the volumes of total pancreas, pancreatic parenchyma, and fat increase linearly with age. From age 20-60 years, pancreas volume reaches a plateau (72.4 6 25.8 cm 3 total; 44.5 6 16.5 cm 3 parenchyma) and then declines thereafter. In adults, total (*32%), parenchymal (*13%), and fat (*68%) volumes increase with obesity. Pancreatic fat content also increases with aging but is not further increased in type-2 diabetes. We provide lifelong population data for total pancreatic, parenchymal, and fat volumes in humans. Although pancreatic fat increases with aging and obesity, it is not increased in type-2 diabetes. Clin. Anat. 20:933-942, 2007. V V C 2007 Wiley-Liss, Inc.

High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8+ cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type-1 thymidine kinase (HSV1-TK) and interleukin (IL)-13 zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it may be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [18F]FHBG imaging was safe and enabled the longitudinal imaging of T cells stably transfected with a PET reporter gene in patients. Further optimization of this imaging approach for monitoring in vivo cell trafficking should greatly benefit various cell-based therapies for cancer.

In this prospective survey of referring physicians, we investigated whether and how Ga-labeled prostate-specific membrane antigen 11 (Ga-PSMA-11) PET/CT affects the implemented management of prostate cancer patients with biochemical recurrence (BCR). We conducted a prospective survey of physicians (NCT02940262) who referred 161 patients with prostate cancer BCR (median prostate-specific antigen value, 1.7 ng/mL; range, 0.05-202 ng/mL). Referring physicians completed one questionnaire before the scan to indicate the treatment plan withoutGa-PSMA-11 PET/CT information (Q1; = 101), one immediately after the scan to denote intended management changes (Q2; = 101), and one 3-6 mo later to document the final implemented management (Q3; = 56). The implemented management was also obtained via electronic chart review or patient contact ( = 45). A complete documented management strategy (Q1 + Q2 + implemented management) was available for 101 of 161 patients (63%). Seventy-six of these (75%) had a positiveGa-PSMA-11 PET/CT result. The implemented management differed from the prescan intended management (Q1) in 54 of 101 patients (53%). The postscan intended management (Q2) differed from the prescan intended management (Q1) in 62 of 101 patients (61%); however, these intended changes were not implemented in 29 of 62 patients (47%). Pelvic nodal and extrapelvic metastatic disease on Ga-PSMA-11 PET/CT (PSMA T0N1M0 and PSMA T0N1M1 patterns) was significantly associated with implemented management changes ( = 0.001 and 0.05). Information fromGa-PSMA-11 PET/CT brings about management changes in more than 50% of prostate cancer patients with BCR (54/101; 53%). However, intended management changes early after Ga-PSMA-11 PET/CT frequently differ from implemented management changes.

BACKGROUND Correct pretreatment classification is critical for optimizing diagnosis and treatment of patients with peripheral nerve sheath tumors (PNSTs). The aim of this study was to evaluate whether F18-fluorodeoxyglucose positron emission tomography (FDG PET) can differentiate malignant (MPNST) from benign PNSTs. METHODS Thirty-four adult patients presenting with PNST who underwent a presurgical FDG PET/computed tomography (CT) scan between February 2005 and November 2008 were included in the study. Tumors were characterized histologically, by FDG maximum standardized uptake value (SUVmax [g/mL]), and by CT size (tumor maximal diameter [cm]). The accuracy of FDG PET for differentiating MPNSTs from benign PNSTs (neurofibroma and schwannoma) was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS SUVmax was measured in 34 patients with 40 tumors (MPNSTs: n = 17; neurofibromas: n = 9; schwannomas: n = 14). SUVmax was significantly higher in MPNST compared with benign PNST (12.0 ± 7.1 vs 3.4 ± 1.8; P < .001). An SUVmax cutoff point of ≥6.1 separated MPNSTs from BPSNTs with a sensitivity of 94% and a specificity of 91% (P < .001). By ROC curve analysis, SUVmax reliably differentiated between benign and malignant PNSTs (area under the ROC curve of 0.97). Interestingly, the difference between MPNSTs and schwannomas was less prominent than that between MPNSTs and neurofibromas. CONCLUSIONS Quantitative FDG PET imaging distinguished between MPNSTs and neurofibromas with high accuracy. In contrast, MPNSTs and schwannomas were less reliably distinguished. Given the difficulties in clinically evaluating PNST and in distinguishing benign PNST from MPNST, FDG PET imaging should be used for diagnostic intervention planning and for optimizing treatment strategies.

Purpose: Change in tumor size as classified by Response Evaluation Criteria in Solid Tumors poorly correlates with histopathologic response to neoadjuvant therapy in patients with softtissue sarcomas. The aim of this study was to prospectively evaluate whether positron emission tomography with 18 F-fluorodeoxyglucose (FDG-PET) allows for a more accurate evaluation of histopathologic response. Experimental Design: From January 2005 to January 2007, 42 patients with resectable biopsy-proven high-grade soft-tissue sarcoma underwent a FDG-PET/computed tomography scan before and after neoadjuvant treatment. Relative changes in tumor FDG uptake and size from the baseline to the follow-up scan were calculated, and their accuracy for assessment of histopathologic response was compared by receiver operating characteristic curve analysis. Histopathologic response was defined as z95% tumor necrosis. Results: In histopathologic responders (n = 8; 19%), reduction in tumor FDG uptake was significantly greater than in nonresponders (P < 0.001), whereas no significant differences were found for tumor size (P = 0.24). The area under the receiver operating characteristic curve for metabolic changes was 0.93, but only 0.60 for size changes (P = 0.004). Using a 60% decrease in tumor FDG uptake as a threshold resulted in a sensitivity of 100% and a specificity of 71% for assessment of histopathologic response, whereas Response Evaluation Criteria in Solid Tumors showed a sensitivity of 25% and a specificity of 100%. Conclusion: Quantitative FDG-PET was significantly more accurate than size-based criteria at assessing histopathologic response to neoadjuvant therapy. FDG-PETshould be considered as a modality to monitor treatment response in patients with high-grade soft-tissue sarcoma.

The interobserver agreement for Ga-PSMA-11 PET/CT study interpretations in patients with prostate cancer is unknown.Ga-PSMA-11 PET/CT was performed in 50 patients with prostate cancer for biochemical recurrence ( = 25), primary diagnosis ( = 10), biochemical persistence after primary therapy ( = 5), or staging of known metastatic disease ( = 10). Images were reviewed by 16 observers who used a standardized approach for interpretation of local (T), nodal (N), bone (Mb), or visceral (Mc) involvement. Observers were classified as having a low (<30 prior Ga-PSMA-11 PET/CT studies; = 5), intermediate (30-300 studies; = 5), or high level of experience (>300 studies; = 6). Histopathology ( = 25, 50%), post-external-beam radiation therapy prostate-specific antigen response ( = 15, 30%), or follow-up PET/CT ( = 10, 20%) served as a standard of reference. Observer groups were compared by overall agreement (% patients matching the standard of reference) and Fleiss' κ with mean and corresponding 95% confidence interval (CI). Agreement among all observers was substantial for T (κ = 0.62; 95% CI, 0.59-0.64) and N (κ = 0.74; 95% CI, 0.71-0.76) staging and almost perfect for Mb (κ = 0.88; 95% CI, 0.86-0.91) staging. Level of experience positively correlated with agreement for T (κ = 0.73/0.66/0.50 for high/intermediate/low experience, respectively), N (κ = 0.80/0.76/0.64, respectively), and Mc staging (κ = 0.61/0.46/0.36, respectively). Interobserver agreement for Mb was almost perfect irrespective of prior experience (κ = 0.87/0.91/0.88, respectively). Observers with low experience, when compared with intermediate and high experience, demonstrated significantly lower median overall agreement (54% vs. 66% and 76%, = 0.041) and specificity for T staging (73% vs. 88% and 93%, = 0.032). The interpretation of Ga-PSMA-11 PET/CT for prostate cancer staging is highly consistent among observers with high levels of experience, especially for nodal and bone assessments. Initial training on at least 30 patient cases is recommended to ensure acceptable performance.

Response rates of unselected non–small cell lung cancer (NSCLC) patients to the epidermal growth factor receptor inhibitor erlotinib are low and range from 10% to 20%. Early response assessments are needed to avoid costs and side effects of inefficient treatments. Here we determined whether early changes in tumor uptake of 18F-FDG can predict progression-free and overall survival in NSCLC patients who are treated with erlotinib. Methods Twenty-two patients (6 men, 16 women; mean age ± SD, 64 ± 13 y) with stage III or stage IV NSCLC who received erlotinib treatment were enrolled prospectively. 18F-FDG PET/CT was performed before the initiation of treatment (n = 22), after 2 wk (n = 22), and after 78 ± 21 d (n = 11). Tumor maximum standardized uptake values were measured for a maximum of 5 lesions for each patient. Tumor responses were classified using modified PET Response Criteria in Solid Tumors (use of maximum standardized uptake values). Median overall survival by Kaplan–Meier analysis was compared between groups using a log-rank test. Results The overall median time to progression was 52 d (95% confidence interval, 47–57 d). The overall median survival time was 131 d (95% confidence interval, 0–351 d). Patients with progressive metabolic disease on early follow-up PET showed a significantly shorter time to progression (47 vs. 119 d; P < 0.001) and overall survival (87 vs. 828 d; P = 0.01) than patients classified as having stable metabolic disease or partial or complete metabolic response. Conclusion These data suggest that 18F-FDG PET/CT performed early after the start of erlotinib treatment can help to identify patients who benefit from this targeted therapy.

Purpose In patients with soft-tissue sarcoma (STS), the early assessment of treatment responses is important. Using positron emission tomography/computed tomography (PET/CT) with [18F]fluorodeoxyglucose (FDG),we determined whether changes in tumor FDG uptake predict histopathologic treatment responses in high-grade STS after the initial cycle of neoadjuvant chemotherapy. Experimental Design From February 2006 to March 2008, 50 patients with resectable high-grade STS scheduled for neoadjuvant therapy and subsequent tumor resection were enrolled prospectively. FDG-PET/CT before (baseline), after the first cycle (early follow-up), and after completion of neoadjuvant therapy (late follow-up) was done. Tumor FDG uptake and changes were measured by standardized uptake values. Histopathologic examination of the resected specimen provided an assessment of treatment response. Patients with ≥95% pathologic necrosis were classified as treatment responders. FDG-PET/CT results were compared with histopathologic findings. Results At early follow-up, FDG uptake decreased significantly more in 8 (16%) responders than in the 42 (84%) nonresponders (−55% versus −23% P = 0.002). All responders and 14 of 42 nonresponders had a ≥35% reduction in standardized uptake value between baseline and early follow-up. Using a ≥35% reduction in FDG uptake as early metabolic response threshold resulted in a sensitivity and specificity of FDG-PET for histopathologic response of 100% and 67%, respectively. Applying a higher threshold at late follow-up improved specificity but not sensitivity. CT had no value at response prediction. Conclusion A 35% reduction in tumor FDG uptake at early follow-up is a sensitive predictor of histopathologic tumor response. Early treatment decisions such as discontinuation of chemotherapy in nonresponding patients could be based on FDG-PET criteria.