Brain positron emission tomography in idiopathic normal-pressure hydrocephalus: new 18 F-fluorodeoxyglucose pattern in a long-known syndrome.

AIM: Patients with idiopathic normal-pressure hydrocephalus (iNPH) can show a global reduction in cerebral glucose metabolism at [ 18 F]Fluorodeoxyglucose (FDG) PET. The presence of caudate hypometabolism has been identified as a potential biomarker in iNPH, yet there is limited evidence of hypermetabolic findings in patients with iNPH so far. METHODS: We retrieved retrospectively patients with iNPH and normal cognitive assessment, evaluated before surgery undergoing brain [ 18 F]FDG-PET. The 18 F-FDG-PET brain scans were compared to those of a control group of healthy subjects, matched for age and sex, by statistical parametric mapping (SPM) to identify areas of relative hypo- and hypermetabolism. Furthermore, the existence of a correlation between areas of hypo- and hypermetabolism in the patient group was tested. RESULTS: Seven iNPH patients (mean age 74 ±â€…6 years) were found in the hospital database. SPM group analysis revealed clusters of significant hypometabolism ( P  = 0.001) in the iNPH group in the dorsal striatum, involving caudate and putamen bilaterally. Clusters of significant hypermetabolism ( P  = 0.001) were revealed in the bilateral superior and precentral frontal gyrus (BA 4, 6). A significant inverse correlation between striatal hypometabolism and bilateral superior and precentral frontal gyrus hypermetabolism was revealed ( P  < 0.001 corrected for multiple comparisons). CONCLUSION: In this cohort, patients with iNPH showed subcortical hypometabolism, including bilateral dorsal striatum. To the best of our knowledge, this is the first report demonstrating a hypermetabolic pattern in the primary motor and premotor areas, and showing an inverse correlation between the striatum and motor cortex in patients with iNPH.

To Enhance or Not to Enhance? The Role of Contrast Medium 18F-FDG PET/CT in Recurrent Ovarian Carcinomas.

Background and Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography/X-ray computed tomography (PET/CT) represents the mainstay diagnostic procedure for suspected ovarian cancer (OC) recurrence. PET/CT can be integrated with contrast medium and in various diagnostic settings; however, the effective benefit of this procedure is still debated. We aimed to compare the diagnostic capabilities of low-dose and contrast-enhanced PET/CT (PET/ldCT and PET/ceCT) in patients with suspected ovarian cancer relapse. Materials and Methods: 122 OC patients underwent both PET/ldCT and PET/ceCT. Two groups of nuclear medicine physicians and radiologists scored the findings as positive or negative. Clinical/radiological follow-up was used as ground truth. Sensitivity, specificity, negative/positive predictive value, and accuracy were calculated at the patient and the lesion level. Results: A total of 455 and 474 lesions were identified at PET/ldCT and PET/ceCT, respectively. At the lesion level, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were not significantly different between PET/ldCT and PET/ceCT (98%, 93.3%, 97.4%, 94.9%, and 96.9% for PET/ldCT; 99%, 95.5%, 98.3%, 97%, and 98% for PET/ceCT, p = ns). At the patient level, no significant differences in these parameters were identified (e.g., p = 0.22 and p = 0.35 for accuracy, in the peritoneum and lymph nodes, respectively). Smaller peritoneal/lymph node lesions close to physiological FDG uptake sources were found in the cases of misidentification by PET/ldCT. PET/ceCT prompted a change in clinical management in four cases (3.2%) compared to PET/ldCT. Conclusions: PET/ceCT does not perform better than PET/ldCT but can occasionally clarify doubtful peritoneal findings on PET/ldCT. To avoid unnecessary dose to the patient, PET/ceCT should be excluded in selected cases.

ERANET JTC 2011: Submission and Activation of an International Academic Translational Project in Advanced Breast Cancer. Experience From the ET-FES Study.

Background: Academic research is important to face unmet medical needs. The Oncological community encounters many hurdles in setting up multicenter investigator-driven trials mainly due to administrative complexity. The purpose of a network organization at a multinational level is to facilitate clinical trials through standardization, coordination, and education for drug development and regulatory approval. Methods: The application of an European grant foresees the creation of a consortium which aims at facilitating multi-center academic clinical trials. Results: The ERA-NET TRANSCAN Call 2011 on "Validation of biomarkers for personalized cancer medicine" was released on December 2011. This project included Italian, Spanish, French and German centers. The approval process included Consortium constitution, project submission, Clinical Trial Submission, and activation on a national level. The different timescales for submitting study documents in each Country and the misalignment of objections by each Competent Authority CA, generated several requests for changes to the study documents which meant amendments had to be made; as requested by the 2001/20/EC Directive, the alignment of core documents is mandatory. This procedure impacted significantly on study activation timelines. Time to first patient in was 14, 10, 28, and 31 months from the date of submission in Italy, France, Spain, and Germany, respectively. Accrual was stopped on 22nd January 2021 due to an 18F FES shortage as the primary reason but also for having exceeded the project deadlines with consequent exhaustion of the funds allocated for the project. Conclusions: Pharmaceutical companies might be reluctant to fund research projects aimed at treatment individualization if the approval for a wider indication has already been achieved. Academic trials therefore become fundamental for promoting trials which are not attractive to big pharma. It was very difficult and time consuming to activate an academic clinical trial, for this reason, a study may become "old" as new drugs entered into the market. National institutions should promote the development of clinical research infrastructures and network with competence in regulatory, ethical, and legal skills to speed up academic research.

Biokinetic and dosimetric aspects of 64CuCl2 in human prostate cancer: possible theranostic implications.

BACKGROUND: The aim of the present study is to evaluate the kinetics and dosimetry of 64CuCl2 in human prostate cancer (PCa) lesions. We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external beam radiation therapy. All patients underwent 64CuCl2-PET/CT to detect PCa recurrence/metastases. Volumes of interest were manually drawn for each 64CuCl2 avid PCa lesion with a diameter > 1 cm on mpMRI in each patient. Time-activity curves for all lesions were obtained. The effective and biological half-life and the standard uptake values (SUVs) were calculated. Tumour/background ratio (TBR) curves as a function of time were considered. Finally, the absorbed dose per lesion was estimated. RESULTS: The mean effective half-life of 64CuCl2 calculated in the lymph nodes (10.2 ± 1.7 h) was significantly higher than in local relapses (8.8 ± 1.1 h) and similar to that seen in bone metastases (9.0 ± 0.4 h). The mean 64CuCl2 SUVmax calculated 1 h after tracer injection was significantly higher in the lymph nodes (6.8 ± 4.3) and bone metastases (6.8 ± 2.9) than in local relapses (4.7 ± 2.4). TBR mean curve of 64CuCl2 revealed that the calculated TBRmax value was 5.0, 7.0, and 6.2 in local relapse and lymph node and bone metastases, respectively, and it was achieved about 1 h after 64CuCl2 injection. The mean absorbed dose of the PCa lesions per administrated activity was 6.00E-2 ± 4.74E-2mGy/MBq. Indeed, for an administered activity of 3.7 GBq, the mean dose absorbed by the lesion would be 0.22 Gy. CONCLUSIONS: Dosimetry showed that the dose absorbed by PCa recurrences/metastases per administrated activity was low. The dosimetric study performed does not take into account the possible therapeutic effect of the Auger electrons. Clinical trials are needed to evaluate 64Cu internalization in the cell nucleus that seems related to the therapeutic effectiveness reported in preclinical studies.

Detection of metastatic bone lesions in breast cancer patients: fused (18)F-Fluoride-PET/MDCT has higher accuracy than MDCT. Preliminary experience.

PURPOSE: So far, no studies comparing (18)F-Fluoride-PET/CT and MDCT for the detection of bone metastases are available. We compared the accuracy of (18)F-Fluoride-PET/CT (MDCT: 3.75 mm thickness-image-reconstruction), whole-body Multi-Detector-CT (MDCT: 1.25 mm thickness-image-reconstruction) and (18)F-Fluoride-PET/MDCT (MDCT: 1.25 mm thickness-image-reconstruction) in identifying bone metastases in breast cancer patients. METHODS: We studied 39 breast cancer patients for bone metastases. Imaging was performed on an integrated PET/MDCT-system; CT images were reconstructed at 3.75 mm and 1.25 mm thickness. Two nuclear medicine physicians and one radiologist interpreted blindly (18)F-Fluoride-PET/CT, (18)F-Fluoride-PET/MDCT and MDCT. MDCT at 12 months served as the standard of reference. RESULTS: Overall, 662 bone lesions were detected in our analysis. Of these, 542 were malignant and 120 were benign according to the standard of reference. (18)F-Fluoride-PET/CT detected 491 bone metastases, 114 (23%) of which displayed no clear morphological changes on MDCT, whereas MDCT detected 416 bone metastases, 39 (9.3%) of which showed no (18)F-Fluoride-PET uptake. Overall sensitivity and specificity were: 91% and 91%, respectively, for (18)F-Fluoride-PET/CT, and 77% and 93% for MDCT. The integrated assessment of (18)F-Fluoride-PET/MDCT yielded sensitivity and specificity values of 98% and 93%, respectively. CONCLUSIONS: (18)F-Fluoride-PET/MDCT has higher diagnostic accuracy than (18)F-Fluoride-PET/CT and MDCT for the evaluation of bone metastases in breast cancer.