BACKGROUND. The aim was to assess the relevant distribution of the novel PET tracer 68Ga‐DOTATATE in neuroendocrine tumors (NETs) with combined positron emission tomography / computed tomography (PET/CT) and compare its performance with that of 18F‐FDG PET/CT. METHODS. The imaging findings with 68Ga‐DOTATATE and 18F‐FDG on 38 consecutive patients with a diagnosis of primary or recurrent NET were compared and correlated with tumor grade on histology based on ki67 and mitotic index. RESULTS. The sensitivity of 68Ga‐DOTATATE PET/CT was 82% (31 of 38) and that of 18F‐FDG PET/CT was 66% (25 of 38). The sensitivity of combined 68Ga‐DOTATATE and 18F‐FDG PET/CT was 92% (35 of 38). There was greater uptake of 68Ga‐DOTATATE than 18F‐FDG in low‐grade NET (median SUV 29 vs 2.9, P < .001). In high‐grade NET there was higher uptake of 18F‐FDG over 68Ga‐DOTATATE (median SUV 11.7 vs 4.4, P = .03). There was a significant correlation with predominant tumor uptake of 68Ga‐DOTATATE or 18F‐FDG and tumor grade on histology (P < .0001). CONCLUSIONS. 68Ga‐DOTATATE PET/CT is a useful novel imaging modality for NETs and is superior to 18F‐FDG for imaging well‐differentiated NET. Functional imaging with both 68Ga‐DOTATATE and 18F‐FDG has potential for a more comprehensive tumor assessment in intermediate‐ and high‐grade tumors. Cancer 2008. ©2008 American Cancer Society.

111 In-diethylenetriaminepentaacetic acid (DTPA)-octreotide scintigraphy is currently the nuclear medicine imaging modality of choice for identifying neuroendocrine tumors. However, there are cohorts of patients in whom scintigraphy findings are negative or equivocal. We evaluated the role of 68 Ga-DOTATATE PET in a selected group of patients with negative or weakly positive findings on 111 In-DTPA-octreotide scintigraphy to determine whether 68 Ga-DOTATATE PET is able to detect additional disease and, if so, whether patient management is altered. Methods: Fifty-one patients with a histologically confirmed diagnosis of neuroendocrine tumors were included. Of the 51 patients, 35 who were negative and 16 equivocal for uptake on 111 In-DTPA-octreotide scintigraphy underwent 68 Ga-DOTATATE PET. Findings were compared using a region-by-region analysis. All findings were verified with CT or MRI. After 68 Ga-DOTATATE PET, all cases were reviewed to determine whether the 68 Ga-DOTATATE PET findings resulted in any alteration in management, in terms of suitability for peptide receptor therapy, somatostatin analogs, and surgery. Results: Of the 51 patients, 47 had evidence of disease on cross-sectional imaging or biochemically. 68 Ga-DOTATATE PET was positive in 41 of these 47 patients (87.2%). No falsepositive lesions were identified. 68 Ga-DOTATATE PET detected 168 of the 226 lesions (74.3%) that were identified with crosssectional imaging. 68 Ga-DOTATATE PET identified significantly more lesions than 111 In-DTPA-octreotide scintigraphy (P , 0.001). There was no correlation between 68 Ga-DOTATATE uptake and histologic grade of neuroendocrine tumors. 68 Ga-DOTATATE imaging changed management in 36 patients (70.6%), who were subsequently deemed suitable for peptide receptor-targeted therapy. Conclusion: In patients with negative or equivocal 111 In-DTPA-octreotide findings, 68 Ga-DOTATATE PET identifies additional lesions and may alter management in most cases.

Purpose: We prospectively examined the role of tumor textural heterogeneity on positron emission tomography/computed tomography (PET/CT) in predicting survival compared with other clinical and imaging parameters in patients with non-small cell lung cancer (NSCLC).Experimental Design: The feasibility study consisted of 56 assessed consecutive patients with NSCLC (32 males, 24 females; mean age 67 AE 9.7 years) who underwent combined fluorodeoxyglucose (FDG) PET/ CT. The validation study population consisted of 66 prospectively recruited consecutive consenting patients with NSCLC (37 males, 29 females; mean age, 67.5 AE 7.8 years) who successfully underwent combined FDG PET/CT-dynamic contrast-enhanced (DCE) CT. Images were used to derive tumoral PET/CT textural heterogeneity, DCE CT permeability, and FDG uptake (SUV max ). The mean follow-up periods were 22.6 AE 13.3 months and 28.5AE 13.2 months for the feasibility and validation studies, respectively. Optimum threshold was determined for clinical stage and each of the above biomarkers (where available) from the feasibility study population. Kaplan-Meier analysis was used to assess the ability of the biomarkers to predict survival in the validation study. Cox regression determined survival factor independence.Results: Univariate analysis revealed that tumor CT-derived heterogeneity (P < 0.001), PET-derived heterogeneity (P ¼ 0.003), CT-derived permeability (P ¼ 0.002), and stage (P < 0Á001) were all significant survival predictors. The thresholds used in this study were derived from a previously conducted feasibility study. Tumor SUV max did not predict survival. Using multivariable analysis, tumor CT textural heterogeneity (P ¼ 0.021), stage (P ¼ 0.001), and permeability (P < 0.001) were independent survival predictors. These predictors were independent of patient treatment.Conclusions: Tumor stage and CT-derived textural heterogeneity were the best predictors of survival in NSCLC. The use of CT-derived textural heterogeneity should assist the management of many patients with NSCLC.

Our purpose was to compare the performance of 68 4,7,N9,N$,N%-tetraacetic acid-D-Phe 1 , Tyr 3 -octreotate (DOTATATE), a novel selective somatostatin receptor 2 PET ligand, and 18 F-FDG in the detection of pulmonary neuroendocrine tumors using PET/CT, with correlation of uptake and tumor grade on histology. Methods: The imaging findings of the first 18 consecutive patients (8 men and 10 women) with pulmonary neuroendocrine tumors (11 typical carcinoids, 2 atypical carcinoids, 1 large cell neuroendocrine tumor, 1 small cell neuroendocrine carcinoma, 1 non-small cell lung cancer with neuroendocrine differentiation, and 2 cases of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia) who underwent 68 Ga-DOTATATE and 18 F-FDG PET/CT were reviewed. In all cases, the diagnosis was established on histology. Results: Of 18 patients, 15 had primary tumors (median size, 2.7 cm; range, 0.5-8 cm) and 3 had recurrent tumors. All typical carcinoids showed high uptake of 68 Ga-DOTATATE (maximum standardized uptake value [SUV max ] $ 8.2), but 4 of 11 showed negative or minimal 18 F-FDG uptake (SUV max 5 1.7-2.9). All tumors of higher grade showed high uptake of 18 F-FDG (SUV max $ 11.7), but 3 of 5 showed only minimal accumulation of 68 Ga-DOTATATE (SUV max 5 2.2-2.8). Neither case of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia showed uptake of 68 Ga-DOTATATE or 18 F-FDG. Typical carcinoids showed significantly higher uptake of 68 Ga-DOTATATE and significantly less uptake of 18 F-FDG than did tumors of higher grade (P 5 0.002 and 0.005). There was no instance of falsepositive uptake of 68 Ga-DOTATATE, but there were 3 sites of 18 F-FDG uptake secondary to inflammation. 68 Ga-DOTATATE was superior to 18 F-FDG in discriminating endobronchial tumor from distal collapsed lung (P 5 0.02). Conclusion: Typical bronchial carcinoids showed higher and more selective uptake of 68 Ga-DOTATATE than of 18 F-FDG. Atypical carcinoids and higher grades had less 68 Ga-DOTATATE avidity but were 18 F-FDG-avid.

The purpose of this study was to evaluate integrated 18 F-FDG PET/CT in patients with idiopathic pulmonary fibrosis (IPF) and diffuse parenchymal lung disease (DPLD). Methods: Thirty-six consecutive patients (31 men and 5 women; mean age 6 SD, 68.7 6 9.4 y) with IPF (n 5 18) or other forms of DPLD (n 5 18) were recruited for PET/CT and high-resolution CT (HRCT), acquired on the same instrument. The maximal pulmonary 18 F-FDG metabolism was measured as a standardized uptake value (SUV max ). At this site, the predominant lung parenchyma HRCT pattern was defined for each patient: ground-glass or reticulation/honeycombing. Patients underwent a global health assessment and pulmonary function tests. Results: Raised pulmonary 18 F-FDG metabolism in 36 of 36 patients was observed. The parenchymal pattern on HRCT at the site of maximal 18 F-FDG metabolism was predominantly ground-glass (7/36), reticulation/ honeycombing (26/36), and mixed (3/36). The mean SUV max in patients with ground-glass and mixed patterns was 2.0 6 0.4, and in reticulation/honeycombing it was 3.0 6 1.0 (MannWhitney U test, P 5 0.007). The mean SUV max in patients with IPF was 2.9 6 1.1, and in other DPLD it was 2.7 6 0.9 (MannWhitney U test, P 5 0.862). The mean mediastinal lymph node SUV max (2.7 6 1.3) correlated with pulmonary SUV max (r 5 0.63, P , 0.001). Pulmonary 18 F-FDG uptake correlated with the global health score (r 5 0.50, P 5 0.004), forced vital capacity (r 5 0.41, P 5 0.014), and transfer factor (r 5 0.37, P 5 0.042). Conclusion: Increased pulmonary 18 F-FDG metabolism in all patients with IPF and other forms of DPLD was observed. Pulmonary 18 F-FDG uptake predicts measurements of health and lung physiology in these patients. 18 F-FDG metabolism was higher when the site of maximal uptake corresponded to areas of reticulation/honeycomb on HRCT than to those with ground-glass patterns.

BACKGROUND: The role of chemotherapy for neuroendocrine tumours remains controversial and there is no standard regimen. METHODS: We report the outcome for a consecutive series of chemonaive patients with metastatic or locally advanced neuroendocrine tumours treated with a combination of 5-fluorouracil (500 mg m À2 ), cisplatin (70 mg m À2 ) and streptozocin (1000 mg m À2 ) (FCiSt) administered three weekly for up to six cycles. Patients were assessed for radiological response, toxicity and survival. RESULTS: In the 79 patients assessable for response, treatment with FCiSt was associated with an overall response rate of 33% (38% for pancreatic primary sites and 25% for non-pancreatic primary sites). Stable disease occurred in a further 51%, with progression in 16%. The median time to progression was 9.1 months and median overall survival was 31.5 months. The most common grade 3 -4 toxicity was neutropaenia (28% patients) but grade 3 -4 infection was rare (7%). The most frequent non-haematological grade 3 -4 toxicity was nausea and vomiting (17%). Prognostic factors included Ki-67, mitotic index, grade and chromogranin A, whereas response to chemotherapy was predicted by mitotic index, grade and a-fetoprotein. CONCLUSION: FCiSt is an effective regimen for neuroendocrine tumours with an acceptable toxicity profile. Grade and mitotic index are the best predictors of response.

These data demonstrate the potential for allogeneic immunotherapy with donor lymphocytes both to reduce relapse risk and to induce durable antitumor responses in patients with Hodgkin's lymphoma after hematopoietic stem-cell transplantation that incorporates in vivo T-cell depletion.

Purpose: To test the hypothesis that sequential 18 F-fluorodeoxyglucose-positron emission tomography/ computed tomography (FDG-PET/CT) is a correlative marker in metastatic clear cell renal cancer (mRCC), patients were treated with sunitinib. Three sequential scans were conducted to determine whether the timing of the investigation was relevant. Experimental Design: Forty-four untreated mRCC patients were enrolled into this prospective phase II study.18 F-FDG-PET/CT scans were conducted before (n ¼ 44) and after 4 weeks (n ¼ 43) and 16 weeks (n ¼ Conclusions: Baseline FDG-PET/CT yields prognostic significant data. FDG-PET/CT responses occur in the majority of patients after 4 weeks of therapy; however, it is not until 16 weeks when the results become prognostically significant.