Efficacy of peptide receptor radionuclide therapy with 177Lu-octreotate in metastatic pulmonary neuroendocrine tumors: a dual-centre analysis.

There is lack of data on the specific benefit of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) of pulmonary origin. This dual- centre study aimed to assess outcome and toxicity of standardized PRRT with 177Lu-octreotate in a patient population of advanced pulmonary NET of grade 1-2. We retrospectively assessed 22 consecutively patients treated with 4 intended cycles at 3 monthly intervals (mean activity per cycle 7.8±0.68 GBq). In a median follow-up period of 54 months, no significant nephrotoxicity (≥ grade 3) was observed. Reversible hematotoxicity (grade 3) occurred in 3 patients (13.6%). Treatment response consisted of partial response in 6 (27.3%), stable disease in 9 (40.9%), and progressive disease in 7 (31.8%) patients. Median progression-free survival (PFS) and overall survival (OS) was 27 (95% CI, 9-45) and 42 months (95% CI, 25-59), respectively. High hepatic tumor load (> 50%) and high plasma chromogranin A (> 600 ng/mL) were negative baseline predictors for PFS and OS on univariate analysis, CgA remained significant on multivariate analysis (PFS, P=0.011; OS, P=0.026). Disease progression despite PRRT was associated with shorter survival (median OS 15 vs 53 mo, P<0.001). Despite a higher incidence of treatment failure compared to NET of other origins, the observed substantial and sustained disease stabilization (median PFS of 27 mo, disease control rate of > 2/3 of pts) indicates considerable efficacy of 177Lu-octreotate in pulmonary NET.

Significance of multiple nodal basin drainage in patients with truncal melanoma.

BACKGROUND: Assessing whether an association exists between drainage to multiple basins and lymphatic metastasis in patients with truncal melanoma (TM). METHODS: The study included 260 patients with primary TM (163 men; median age 56.5 y/o) with a cN0 M0, who underwent a sentinel lymph node scintigraphy and biopsy. The median tumor thickness (TT) was 1.51 mm. RESULTS: One hundred and three patients showed more than one basin; of these, 95 patients had 2 basins, 6 had 3 basins, and 2 had 4 basins of drainage. Nodal histology was positive for metastatic disease in 65 patients, of whom, 40 had 1 basin, 24 had 2 basins and 1 had 3 basins of drainage. Of the 195 node-negative patients, 116 had 1 basin, 70 had 2 basins, 5 had 3 basins, and 2 had 4 basins of drainage (P=0.89). In a median follow-up of 36 months, 26 patients showed progressive disease, of whom 15 had 1 basin and 11 had 2 basins (P=0.76). Twenty patients died, of whom 11 had 1 basin and 9 had 2 basins (P=0.8). CONCLUSIONS: There is no significant association between the number of drainage basins and sentinel node positivity or further progress of the disease in patients with TM.

Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment.

OBJECTIVE: To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects. METHOD: [¹8F]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested. RESULTS: The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline. CONCLUSION: The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.

Sentinel lymph node status as most important prognostic factor in patients with high-risk cutaneous melanomas (tumour thickness >4.00 mm): outcome analysis from a single institution.

PURPOSE: Sentinel lymph node biopsy (SLNB) is considered the most powerful prognostic indicator of survival in patients with cutaneous melanoma of intermediate thickness (1-4 mm). The use of SLNB in patients with melanoma with a tumour thickness >4.0 mm is still controversial. The purpose of the current study was to determine the prognostic value of SLNB in patients with thick cutaneous melanomas (tumour thickness >4.0 mm) in terms of progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective single-centre study was performed at the Department of Dermatology and Allergy, University of Bonn, and the Department of Nuclear Medicine, University of Bonn, based on data collected between September 2000 and January 2010. A total of 142 patients with cutaneous melanoma of thickness >4.00 mm were identified, and 63 of these patients underwent SLNB. RESULTS: Of the 63 patients in whom SLNB was performed, 25 (39.7 %) had a positive SLN. Ulceration was more frequent in SLN-positive patients (44 %) than in SLN-negative patients (18.4 %). The mean follow-up time for the 63 patients was 50.7 months. Positive SLN status predicted a significantly reduced life expectancy in the analyses of PFS and OS. In SLN-positive patients 5-year OS was 76 % and in SLN-negative patients was 84.2 % (p = 0.048). Patients with a combination of ulcerated tumour and positive SLN had the worst prognosis. CONCLUSION: On the basis of our follow-up data, SLNB has to be recommended in patients with a tumour thickness >4.00 mm after exclusion of lymph node macrometastases or distant metastases. SLN status is the most significant prognostic factor in this group of patients.

The value of F-18 FDG PET in patients with primary sclerosing cholangitis and cholangiocarcinoma using visual and semiquantitative analysis.

AIM: The aim of this study was to assess the value of 18F-fluorodeoxyglucose positron emission tomography (F-18 FDG PET) in patients with suspected cholangiocarcinoma (CC). METHODS: Sixty-five patients with suspected CC were included in this retrospective study. All patients had whole-body FDG PET/CT imaging at a mean time of 100 minutes after administration of FDG injection. PET studies were analyzed using visual analysis and semiquantitative analysis. Semiquantitative analysis was performed using maximum standardized uptake value (SUVmax) and tumor-to-normal liver (T/N) ratio. Malignancy was defined using the following criteria: (1) Visual analysis; (2) SUVmax >3.9; (3) T/N >1.6. Analysis of variance test and receiver operating characteristic analysis were used in statistical analysis. P < 0.05 was considered significant. RESULTS: Follow-up revealed 47 patients with CC. The average SUVmax in CC tumors was 8 ± 2.9 versus 3 ± 1 in benign lesions (P < 0.0001). The average T/N in malignant lesions was 3.5 ± 1.8 versus 1.3 ± 0.4 in benign lesions (P < 0.0001). Sensitivity, specificity, and accuracy for the 3 criteria were as follows: (1) 96%, 67%, and 88%; (2) 94%, 83%, and 91%; (3) 89%, 78%, and 86%. CONCLUSION: F-18 FDG PET semiquantitative analysis using SUVmax >3.9 as criterion for malignancy could improve the diagnostic accuracy in differentiating malignant from benign lesions in patients with suspected CC.

Impact of dual-time-point F-18 FDG PET/CT in the assessment of pleural effusion in patients with non-small-cell lung cancer.

AIM: The aim of this study was to assess the utility of dual-time-point F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) in differentiating benign from malignant pleural disease, in patients with non-small-cell lung cancer. METHODS: A total of 61 patients with non-small-cell lung cancer and pleural effusion were included in this retrospective study. All patients had whole-body FDG PET/CT imaging at 60 ± 10 minutes post-FDG injection, whereas 31 patients had second-time delayed imaging repeated at 90 ± 10 minutes for the chest. Maximum standardized uptake values (SUV(max)) and the average percent change in SUV(max) (%SUV) between time point 1 and time point 2 were calculated. Malignancy was defined using the following criteria: (1) visual assessment using 3-points grading scale; (2) SUV(max) ≥2.4; (3) %SUV ≥ +9; and (4) SUV(max) ≥2.4 and/or %SUV ≥ +9. Analysis of variance test and receiver operating characteristic analysis were used in statistical analysis. P < 0.05 was considered significant. RESULTS: Follow-up revealed 29 patient with malignant pleural disease and 31 patients with benign pleural effusion. The average SUV(max) in malignant effusions was 6.5 ± 4 versus 2.2 ± 0.9 in benign effusions (P < 0.0001). The average %SUV in malignant effusions was +13 ± 10 versus -8 ± 11 in benign effusions (P < 0.0004). Sensitivity, specificity, and accuracy for the 5 criteria were as follows: (1) 86%, 72%, and 79%; (2) 93%, 72%, and 82%; (3) 67%, 94%, and 81%; (4) 100%, 94%, and 97%. CONCLUSIONS: Dual-time-point F-18 FDG PET can improve the diagnostic accuracy in differentiating benign from malignant pleural disease, with high sensitivity and good specificity.

[Targeted radionuclide therapy for patients with metastatic medullary thyroid carcinoma].

OBJECTIVE: To evaluate the effect of 90Y-DOTATOC and 131I-MIBG in treatment of metastatic medullary thyroid carcinoma (MTC). METHODS: Twelve histologically confirmed patients with metastatic MTC were included. All patients underwent both 111In-DTPA-octreotide imaging and 131I/ 123I-meta-iodobenzylguanidine (MIBG) imaging. According to the results of the combined imaging, positive patients were selected to be treated with 90Y-DOTA-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) or 131I-MIBG, respectively. The therapeutic procedures of targeted internal radiation were performed with 3.33 GBq 90Y-DOTATOC at 6-week intervals, or 11.1 GBq 131I-MIBG with a minimum interval of three months. RESULTS: The imaging procedure was positive in all 12 patients: 111In-DTPA-octreotide imaging in eight patients, 131I/ 123I-MIBG imaging in six patients. According to the results of combined imaging, we identified four patients to be treated with 90Y-DOTATOC, and five patients with 131 I-MIBG. After three to five sessions of treatment, three patients with partial remission and six with stable disease were observed. The effective rate was 3/9 (33.3%) and the overall tumor response rate was 9/9 (100%). No relevant toxicity was observed. CONCLUSION: The combined imaging technique can be used to identify patients for effective radionuclide treatment. The treatment with 90Y-DOTATOC or 131I-MIBG is well tolerated and may improve the fate of patients with metastatic MTC.

Steam sterilization and automatic dispensing of [18F]fludeoxyglucose (FDG) for injection.

UNLABELLED: For the purpose of implementing steam sterilization of 2-[18F]FDG (FDG) in the final container into routine production, we have validated and established a fully automated dispensing and sterilization system, thereby considerably reducing the radiation burden to the personnel. METHODS: The commercially available system combines aseptic dispensing of the product solution under a miniaturized laminar flow unit with subsequent steam sterilization, realized by heating of the product in the final containers by an autoclave included in the dispensing unit, thus incorporating current pharmaceutical manufacturing standards for the production of parental radiopharmaceuticals. The efficiency of the used sterilization cycle, the stability of FDG under the conditions of sterilization and the stability of the final product towards radiolysis was investigated with respect to various pH-formulations. RESULTS: The system was found to be fully valid for filling of vials in a laminar flow class A (US-class 100) environment and for sterilization of FDG in the final container. The pH for sterilizing FDG solutions must be slightly acidic to avoid decomposition. A pH of 5.5 appears to be optimal and gives FDG of very high radiochemical purity (approximately 99%). In addition, radiolysis of FDG in solutions of high activity concentration was significantly lower at pH 5.5 than at neutral pH. CONCLUSION: Terminal sterilization enables the production of FDG in full compliance with GMP-regulations even in Class C or D (US class 10,000 or 100,000) laboratories.

The role of combined imaging in metastatic medullary thyroid carcinoma: 111In-DTPA-octreotide and 131I/123I-MIBG as predictors for radionuclide therapy.

PURPOSE: The medical treatment of metastatic medullary thyroid carcinoma (MTC) is still questionable. The aim of this study was to evaluate a combined imaging protocol using 111In-DTPA-octreotide and 131I/123I-MIBG to decide whether targeted radiotherapy would be useful, and which radiopharmaceutical (90Y-DOTATOC or 131I-MIBG) would be more effective. METHODS: Eight patients (four men, four women; mean age 61 years) with metastatic MTC were included. Treatments were performed with 3,330 MBq 90Y-DOTATOC at 6-week intervals, or 11.1 GBq 131I-MIBG with a minimum interval of 3 months. RESULTS: The imaging procedure was positive in all eight patients: 111In-DTPA-octreotide imaging in five patients, 131I/123I-MIBG imaging in four patients. With respect to the number of metastatic lesions, MIBG imaging was less effective than octreotide. According to the results of combined imaging, we identified one patient to be treated with 90Y-DOTATOC, and three patients with 131I-MIBG. An overall antitumor effect was observed in all four patients, one with partial remission and three with stable disease. No relevant toxicity was observed. CONCLUSIONS: The combined imaging can increase the detection rate of metastatic foci in patients with MTC and identify more patients for effective radionuclide treatment. The treatment with 90Y-DOTATOC or 131I-MIBG is well tolerated and may improve the fate of patients with metastatic MTC.