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Diagnostic accuracy in FDG-PET imaging highly depends on the operating procedures. In this clinical study on dementia, we compared the diagnostic accuracy at a single-subject level of a) Clinical Scenarios, b) Standard FDG Images and c) Statistical Parametrical (SPM) Maps generated via a new optimized SPM procedure. We evaluated the added value of FDG-PET, either Standard FDG Images or SPM Maps, to Clinical Scenarios. In 88 patients with neurodegenerative diseases (Alzheimer's Disease—AD, Frontotemporal Lobar Degeneration—FTLD, Dementia with Lewy bodies—DLB and Mild Cognitive Impairment—MCI), 9 neuroimaging experts made a forced diagnostic decision on the basis of the evaluation of the three types of information. There was also the possibility of a decision of normality on the FDG-PET images. The clinical diagnosis confirmed at a long-term follow-up was used as the gold standard. SPM Maps showed higher sensitivity and specificity (96% and 84%), and better diagnostic positive (6.8) and negative (0.05) likelihood ratios compared to Clinical Scenarios and Standard FDG Images. SPM Maps increased diagnostic accuracy for differential diagnosis (AD vs. FTD; beta 1.414, p = 0.019). The AUC of the ROC curve was 0.67 for SPM Maps, 0.57 for Clinical Scenarios and 0.50 for Standard FDG Images. In the MCI group, SPM Maps showed the highest predictive prognostic value (mean LOC = 2.46), by identifying either normal brain metabolism (exclusionary role) or hypometabolic patterns typical of different neurodegenerative conditions., Highlights • Brain FDG-PET was evaluated with a new optimized SPM procedure in dementias. • We compared the diagnostic accuracy of clinical information, visual and SPM FDG-PET. • SPM had the best sensitivity (96%), specificity (84%) and positive and negative LR. • In an MCI subgroup, SPM had the highest predictive prognostic value.

PURPOSE: Detection of recurrence in prostate cancer patients with biochemical failure after radical prostatectomy by [(11)C]choline PET/CT depends on the prostate-specific antigen (PSA) level. The role of other clinical and pathological variables has not been explored. METHODS: A total of 2,124 prostate cancer patients referred to our Institution for [(11)C]choline PET/CT from December 2004 to January 2007 for restaging of disease were retrospectively considered for this study. Inclusion criteria were: previous treatment by radical prostatectomy, and biochemical failure, defined as at least two consecutive PSA measurements of >0.2 ng/ml. These criteria were met for 358 patients. Binary logistic analysis was used to investigate the predictive factors of [(11)C]choline PET/CT. PET/CT findings were validated using criteria based on histological analysis, and follow-up clinical and imaging data. Receiver operating characteristic (ROC) analysis was used to assess the performance of [(11)C]choline PET/CT in relation to PSA levels. RESULTS: The mean PSA level was 3.77 +/- 6.94 ng/ml (range 0.23-45 ng/ml; median 1.27 ng/ml). PET/CT was positive for recurrence in 161 of 358 patients (45%). On an anatomical region basis, [(11)C]choline pathological uptake was observed in lymph nodes (107/161 patients, 66%), prostatectomy bed (55/161 patients, 34%), and in the skeleton (46/161 patients, 29%). PET/CT findings were validated using histological criteria (46/358, 13%), and follow-up clinical and imaging criteria (312/358, 87%). Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were, respectively, 85%, 93%, 91%, 87%, and 89%. In multivariate analysis, high PSA levels, advanced pathological stage, previous biochemical failure and older age were significantly (P < 0.05) associated with an increased risk of positive PET/CT findings. The percentage of positive scans was 19% in those with a PSA level between 0.2 and 1 ng/ml, 46% in those with a PSA level between 1 and 3 ng/ml, and 82% in those with a PSA level higher than 3 ng/ml. ROC analysis showed that PET/CT-positive and PET/CT-negative patients could be best distinguished using a PSA cut-off value of 1.4 ng/ml. CONCLUSIONS: In addition to PSA levels, pathological stage, previous biochemical failure and age should be considered by physicians when referring prostate cancer patients with biochemical failure after radical prostatectomy to [(11)C]choline PET/CT.

Purpose: To present the state-of-art of radiomics in the context of pancreatic neuroendocrine tumors (PanNETs), with a focus on the methodological and technical approaches used, to support the search of guidelines for optimal applications. Furthermore, an up-to-date overview of the current clinical applications of radiomics in the field of PanNETs is provided. Methods: Original articles were searched on PubMed and Science Direct with specific keywords. Evaluations of the selected studies have been focused mainly on (i) the general radiomic workflow and the assessment of radiomic features robustness/reproducibility, as well as on the major clinical applications and investigations accomplished so far with radiomics in the field of PanNETs: (ii) grade prediction, (iii) differential diagnosis from other neoplasms, (iv) assessment of tumor behavior and aggressiveness, and (v) treatment response prediction. Results: Thirty-one articles involving PanNETs radiomic-related objectives were selected. In regard to the grade differentiation task, yielded AUCs are currently in the range of 0.7–0.9. For differential diagnosis, the majority of studies are still focused on the preliminary identification of discriminative radiomic features. Limited information is known on the prediction of tumors aggressiveness and of treatment response. Conclusions: Radiomics is recently expanding in the setting of PanNETs. From the analysis of the published data, it is emerging how, prior to clinical application, further validations are necessary and methodological implementations require optimization. Nevertheless, this new discipline might have the potential in assisting the current urgent need of improving the management strategies in PanNETs patients.

The aim of the present study is to investigate the synergic role of 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI in prostate cancer (PCa) staging. We present pilot data on twenty-two patients with biopsy-proven PCa that underwent 68Ga-PSMA PET/MRI for staging purposes, with 19/22 also undergoing 68Gaa-DOTA-RM2 PET/MRI. TNM classification based on image findings was performed and quantitative imaging parameters were collected for each scan. Furthermore, twelve patients underwent radical prostatectomy with the availability of histological data that were used as the gold standard to validate intraprostatic findings. A DICE score between regions of interest manually segmented on the primary tumour on 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and on T2 MRI was computed. All imaging modalities detected the primary PCa in 18/19 patients, with 68Ga-DOTA-RM2 PET not detecting any lesion in 1/19 patients. In the remaining patients, 68Ga-PSMA and MRI were concordant. Seven patients presented seminal vesicles involvement on MRI, with two of these being also detected by 68Ga-PSMA, and 68Ga-DOTA-RM2 PET being negative. Regarding extraprostatic disease, 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI resulted positive in seven, four and five patients at lymph-nodal level, respectively, and at a bone level in three, zero and one patients, respectively. These preliminary results suggest the potential complementary role of 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI in PCa characterization during the staging phase.

Purpose: The aim of the present systematic review was to provide an overview on the different positron emission tomography (PET) hypoxia radiotracers in the clinical setting of lung cancer. Methods: We performed a comprehensive literature review on the role of PET hypoxia imaging in lung cancer using the electronic databases PubMed and Scopus to select English written language articles on humans from January 2007 to February 2017. The following keywords have been used: “hypoxia” or “hypoxic” and “PET” and “lung cancer”. Reviews, clinical reports, and editorial articles were excluded. Results: Originally, we considered 76 manuscripts, coming to a selection of 37 original articles. In particular, the selected original articles included the following PET radiotracer categories: nitroimidazole compounds, glucose analogue and bis(thiosemicarbazone) complexes. PET radiotracers, particularly nitroimidazole compounds, are the most suitable method to directly identify the presence of hypoxia in lung cancer. Conclusions: Based on the literature review, the definition of the role of clinical application of PET hypoxia radiotracers has been provided reporting that in vivo hypoxia imaging is needed for effective treatment selection, individual treatment planning, and treatment monitoring in oncology.

Objective. [18F]Fluorodeoxyglucose (18F-FDG) PET/CT is increasingly used to assess organ involvement and response to treatment in IgG4-related disease (IgG4-RD), but clear correlations between 18F-FDG uptake and disease activity have not been established yet. We aimed to correlate the intensity and distribution of 18F-FDG uptake with validated clinical, serological and immunological parameters of IgG4-RD activity. Methods. Twenty patients with active IgG4-RD underwent a baseline 18F-FDG PET/CT. Ten patients repeated 18F-FDG PET/CT after immunosuppressive treatments. 18F-FDG tissue uptake was measured using the standardized uptake value corrected for the partial volume effect (PVC-SUV) and the total lesion glycolysis (TLG) with (TLGtot+ln) and without (TLGtot-ln) lymph nodes. Disease activity was assessed by means of clinical parameters [IgG4-RD Responder Index (RI)], serological (ESR and CRP) and immunological (serum IgG4 and circulating plasmablasts) biomarkers. The enhanced liver fibrosis score was exploited as a biomarker for fibroblast activation. Results. Thirteen (65%) patients had two or more organs affected by IgG4-RD. All patients had active IgG4-RD as defined by a median IgG4-RD RI value of 9 (range 6-15; normal < 3). Serum IgG4 and plasmablasts were elevated in 85% of patients. Circulating plasmablasts positively correlated with PVCSUV (P = 0.027), inversely correlated with TLGtot-ln (P = 0.023) and did not correlate with TLGtot+ln (P > 0.05). No statistically significant correlation was found between PVC-SUV or TLG and IgG4-RD RI, ESR, CRP, serum IgG4 or enhanced liver fibrosis score (P > 0.05). Clinical response to immunosuppressive therapies was associated with a consensual reduction of circulating plasmablasts, PVC-SUV, TLGtot+ln and TLGtot-ln values (P < 0.05 for all comparisons). Conclusions. 18F-FDG uptake of IgG4-RD lesions reflects immunological perturbations of the B cell compartment rather than fibroblast activation and extracellular matrix deposition. Conventional biomarkers of disease activity, namely IgG4-RD RI, ESR, CRP and serum IgG4 levels, do not appear to correlate with the radiometabolic activity of IgG4-RD lesions. In light of our results PET/CT represents a reliable instrument for assessing IgG4-RD activity, although lymph-node uptake deserves careful interpretation

A progressive loss of dopamine neurons in the substantia nigra (SN) is considered the main feature of idiopathic Parkinson's disease (PD). Recent neuropathological evidence however suggests that the axons of the nigrostriatal dopaminergic system are the earliest target of α-synuclein accumulation in PD, thus the principal site for vulnerability. Whether this applies to in vivo PD, and also to the mesolimbic system has not been investigated yet. We used [11C]FeCIT PET to measure presynaptic dopamine transporter (DAT) activity in both nigrostriatal and mesolimbic systems, in 36 early PD patients (mean disease duration in months ± SD 21.8 ± 10.7) and 14 healthy controls similar for age. We also performed anatomically-driven partial correlation analysis to evaluate possible changes in the connectivity within both the dopamine networks at an early clinical phase. In the nigrostriatal system, we found a severe DAT reduction in the afferents to the dorsal putamen (DPU) (η2 = 0.84), whereas the SN was the less affected region (η2 = 0.31). DAT activity in the ventral tegmental area (VTA) and the ventral striatum (VST) were also reduced in the patient group, but to a lesser degree (VST η2 = 0.71 and VTA η2 = 0.31). In the PD patients compared to the controls, there was a marked decrease in dopamine network connectivity between SN and DPU nodes, supporting the significant derangement in the nigrostriatal pathway. These results suggest that neurodegeneration in the dopamine pathways is initially more prominent in the afferent axons and more severe in the nigrostriatal system. Considering PD as a disconnection syndrome starting from the axons, it would justify neuroprotective interventions even if patients have already manifested clinical symptoms., Highlights • In vivo study of mesolimbic and nigrostriatal dopamine systems in early iPD • Evidence for a severe axonal damage with relative sparing of SN • Evidence for a moderate damage of the mesolimbic pathway in early iPD • Significant reduction of molecular connectivity between nigrostriatal nodes • Justification for neuroprotective interventions in early-iPD phase

[11C]PIB is the most used amyloid plaques-specific positron-emitting radiotracers. The radiosynthesis of this compound, carried out by methylation of its precursor with [11C]methyl triflate in 2-butanone, has been improved optimizing the initial concentration and the purification method. Two HPLC methods were compared: good radiochemical yields, specific activities, and chemical purity above 98% were achieved by using as eluant acetonitrile/citrate and formulation in 10% ethanol.

Purpose: To evaluate, in prostate cancer (PCa) patients the potential of 11C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed. Methods: We enrolled 83 PCa patients (mean age 68 years, range 51 - 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 - 187.00 ng/ml; PSA0) who showed pathological findings on 11C-choline PET/CT only at the LN site. 11C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT0). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT0 were treated with high doses using SIB. Doses were in the range 36 - 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 - 365 days), serum PSA was measured in all patients (PSA 1) and compared with PSA0 to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT1) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity. Results: PET/CT0 revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA0, PSA1 (mean 6.28 ng/ml, range 0.00 - 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT1, 20 showed a complete metabolic response at the treated area, 22 a partial metabolic response, 3 progression of disease and 2 stable disease. HTT with SIB was well tolerated in all patients. Grade 3 acute toxicity in the genitourinary tract was observed in two patients. Conclusion: 11C-Choline PET/CT is a valuable tool for planning and monitoring HTT in LN relapse after primary treatment. High-dose hypofractionated 11C-choline PET/CT-guided HTT with SIB is well tolerated and is associated with a high early biochemical response rate. © 2014 Springer-Verlag.

Purpose\ud To assess the value of 18F-Fluorodeoxyglucose (18F-FDG) PET Radiomic Features (RF) in predicting Distant Relapse Free Survival (DRFS) in patients with Locally Advanced Pancreatic Cancer (LAPC) treated with radio-chemotherapy.\ud \ud Materials & methods\ud One-hundred-ninety-eight RFs were extracted using IBSI (Image Biomarker Standardization Initiative) consistent software from pre-radiotherapy images of 176 LAPC patients treated with moderate hypo-fractionation (44.25 Gy, 2.95 Gy/fr). Tumors were segmented by applying a previously validated semi-automatic method. One-hundred-twenty-six RFs were excluded due to poor reproducibility and/or repeatability and/or inter-scanner variability. The original cohort was randomly split into a training (n = 116) and a validation (n = 60) group. Multi-variable Cox regression was applied to the training group, including only independent RFs in the model. The resulting radiomic index was tested in the validation cohort. The impact of selected clinical variables was also investigated.\ud \ud Results\ud The resulting Cox model included two first order RFs: Center of Mass Shift (COMshift) and 10th Intensity percentile (P10) (p = 0.0005, HR = 2.72, 95%CI = 1.54–4.80), showing worse outcomes for patients with lower COMshift and higher P10. Once stratified by quartile values (highest quartile vs the remaining), the index properly stratified patients according to their DRFS (p = 0.0024, log-rank test). Performances were confirmed in the validation cohort (p = 0.03, HR = 2.53, 95%CI = 0.96–6.65). The addition of clinical factors did not significantly improve the models’ performance.\ud \ud Conclusions\ud A radiomic-based index including only two robust PET-RFs predicted DRFS of LAPC patients after radio-chemotherapy. The current results could find relevant applications in the treatment personalization of LAPC. A multi-institution independent validation has been planned.

Purpose: To present the progresses of hybrid 18F-FDG PET/MR imagingin the staging/restaging setting of endometrial cancer (EC), with particular focus on performance evaluations and biomarker analyses. Methods: Original articles were searched on PubMed, EMBASE and Web of Science, until March 2021. Reports were screened to select studies using simultaneous PET/MR acquisition, discarding those using sequential protocols. Studies including heterogeneous and/or homogeneous cohorts of pelvic tumor patients were considered, while works for which the exact number of EC patients was not reported have been discarded. Evaluations of selected articles were focused on (i) performance evaluation, (ii) biomarker analysis. The quality of papers was assessed by QUADAS-2. Results: Eleven articles involving 18F-FDGPET/MRI EC-related objectives were selected. The quality of papers was generally high. Compared to other imaging techniques, PET/MRI seems to show a higher diagnostic accuracy in detecting soft tissue invasion and abdominopelvic metastases from primary EC. Among different PET- and MRI-derived biomarkers, SUV-to-ADC ratio seems to be the most informative index in differentiating EC aggressiveness. Moreover, PET/MRI provided the chance to differentiate post-therapeutic changes from local relapse, and to detect small, morphologically unsuspicious lymph node metastases in patients with recurrent EC, with better performances compared to other imaging modalities. Conclusions: Preliminary results demonstrated how 18F-FDG PET/MRI could be a valid imaging technique in patients with EC, both in staging and restaging, also considering the limited radiation exposure. From the limited availability of the existing literature, it is clear that further prospective trials on larger and homogeneous cohorts are needed.

BACKGROUND To investigate the correlation between 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET data and hypoxia immunohistochemical markers in patients with high-grade glioma (HGG). PATIENTS AND METHODS Prospective study including 20 patients with brain MRI suggestive for HGG and undergoing 18F-FAZA PET/CT before treatment for hypoxia assessment. For each 18F-FAZA PET scan SUVmax, SUVmean and 18F-FAZA tumour volume (FTV) at 40, 50 and 60% threshold of SUVmax were calculated; hypoxic volume was estimated by applying different thresholds (1.2, 1.3 and 1.4) to tumour/blood ratio. Seventeen patients were analysed. The immunohistochemical analysis assessed the following parameters: hypoxia-inducible factor 1α, carbonic anhydrase IX (CA-IX), glucose transporter-1, tumour vascularity and Ki-67. RESULTS 18F-FAZA PET showed a single lesion in 15/17 patients and multiple lesions in 2/17 patients. Twelve/17 patients had grade IV glioma and 5/17 with grade III glioma. Bioptic and surgical samples have been analysed separately. In the surgical subgroup (n = 7) a positive correlation was observed between CA-IX and SUVmax (P = 0.0002), SUVmean40 (P = 0.0058), SUVmean50 (P = 0.009), SUVmean60 (P = 0.0153), FTV-40-50-60 (P = 0.0424) and hypoxic volume1.2-1.3-1.4 (P = 0.0058). In the bioptic group (n = 10) tumour vascularisation was inversely correlated with SUVmax (P = 0.0094), SUVmean40 (P = 0.0107), SUVmean50 (P = 0.0094) and SUVmean60 (P = 0.0154). CONCLUSIONS The correlation of 18F-FAZA PET parameters with CD31 and CA-IX represents a reliable method for assessing tumour hypoxia in HGG. The inverse correlation between tumour vascularisation, SUVmax and SUVmean suggest that highly vascularized tumours might present more oxygen supply than hypoxia.

Background. Myocarditis lacks systematic characterization in COVID-19 patients. Methods. We enrolled consecutive patients with newly diagnosed myocarditis in the context of COVID-19 infection. Diagnostic and treatment strategies were driven by a dedicated multidisciplinary disease unit for myocarditis. Multimodal outcomes were assessed during prospective follow-up. Results. Seven consecutive patients (57% males, age 51 ± 9 y) with acute COVID-19 infection received a de novo diagnosis of myocarditis. Endomyocardial biopsy was of choice in hemodynamically unstable patients (n = 4, mean left ventricular ejection fraction (LVEF) 25 ± 9%), whereas cardiac magnetic resonance constituted the first exam in stable patients (n = 3, mean LVEF 48 ± 10%). Polymerase chain reaction (PCR) analysis revealed an intra-myocardial SARS-CoV-2 genome in one of the six cases undergoing biopsy: in the remaining patients, myocarditis was either due to other viruses (n = 2) or virus-negative (n = 3). Hemodynamic support was needed for four unstable patients (57%), whereas a cardiac device implant was chosen in two of four cases showing ventricular arrhythmias. Medical treatment included immunosuppression (43%) and biological therapy (29%). By the 6-month median follow-up, no patient died or experienced malignant arrhythmias. However, two cases (29%) were screened for heart transplantation. Conclusions. Myocarditis associated with acute COVID-19 infection is a spectrum of clinical manifestations and underlying etiologies. A multidisciplinary approach is the cornerstone for tailored management.

Background: The accurate detection of nodal invasion is an unmet need in the clinical staging of renal cancer. Positron emission tomography (PET) with 18F-fluoroazomycin arabinoside (18F-FAZA), a hypoxia specific tracer, is a non-invasive imaging method that detects tumour hypoxia. The aim of this work was to evaluate the role of 18F-FAZA PET/CT in the identification of lymph node metastases in renal cancer. Methods: A proof-of-concept phase 2 study including 20 kidney cancer patients (ClinicalTrials.gov Identifier: NCT03955393) was conducted. Inclusion criteria were one or more of the following three criteria: (1) clinical tumour size > 10cm, (2) evidence of clinical lymphadenopathies at preoperative CT scan and (3) clinical T4 cancer. Before surgery, 18F-FAZA PET/CT was performed, 2h after the intravenous injection of the radiotracer. An experienced nuclear medicine physician, aware of patient’s history and of all available diagnostic imaging, performed a qualitative and semi-quantitative analysis on 18F-FAZA images. Histopathological analysis was obtained in all patients on surgical specimen. Results: Fourteen/19 (74%) patients had a non-organ confined renal cell carcinoma (RCC) at final pathology (either pT3 or pT4). Median number of nodes removed was 12 (IQR 7–15). The rate of lymph node invasion was 16%. No patient with pN1 disease showed positive 18F-FAZA PET, thus suggesting the non-hypoxic behaviour of the lesions. In addition, neither primary tumour nor distant metastases presented a pathological 18F-FAZA uptake. No adverse events were recorded during the study. Conclusions: 18F-FAZA PET/CT scan did not detect RCC lymph neither nodal nor distant metastases and did not show any uptake in the primary renal tumour.

Background The aim of the present study is to explore the correlation between PET and MRI parameters of primary tumour and clinicopathological features and to determine their synergic predictive role in patients with endometrial cancer candidate to surgery. Methods Retrospective study including 27 patients with endometrial cancer and preoperative 18F-fluorodeoxyglucose (18F-FDG)-PET and MRI scan. The following parameters, calculated on the primary tumour, were used for analysis: maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) for PET scans; mean apparent diffusion coefficient (ADCmean) and volume index for MRI scans. FIGO stage, grade, histotype, lymphovascular space invasion (LVSI) and myometrial invasion were the considered clinicopathological features. Results MRI volume index was a good predictor for deep myometrial invasion [area under the curve (AUC) = 0.85; P = 0.003] and for LVSI (AUC = 0.74; P = 0.039). A cutoff value of 9.555 for MRI volume index was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%); a cutoff of 12.165 was predictive for LVSI (sensitivity = 69.2%; specificity = 83.3%). A TLG cutoff value of 26.03 was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%). A high-direct correlation was found with MRI volume index (rho = 0.722; P < 0.001); low-direct correlation with SUVmax (rho = 0.484; P = 0.012), SUVmean (rho = 0.47; P = 0.015) and TLG (rho = 0.482; P = 0.013) were identified. The SUVmax/ADCmean ratio showed a low-direct correlation with percentage of myometrial invasion (rho = 0.467; P = 0.016). Conclusion Volume index, TLG and SUVmax/ADCmean ratio are associated with deep myometrial invasion. As myometrial invasion is the index used to predict lymph node involvement in endometrial cancer, the synergic use of these imaging parameters may be suggested to predict lymphnodal metastases.

Objective: Several studies have reported about the performance of C-choline-PET/computed tomography (CT) (choline) in patients with biochemical recurrent (BCR) prostate cancer, but there is a lack of information regarding negative choline in the same clinical setting. Our aim was to retrospectively analyse negative choline in a cohort of BCR-patients with high prostate-specific antigen (PSA). Methods and results: We retrospectively analysed all choline-scans performed at two high-volume imaging centres between 2005 and 2018, selecting those of interest according to the following inclusion criteria: (1) proven prostate cancer treated either with radical prostatectomy or primary external beam radiation therapy (EBRT), (2) BCR after radical prostatectomy or EBRT, (3) PSA serum values >20 ng/mL at the time of scan and (4) scan reported as negative for active disease. Overall, among 5792 scans performed for BCR-prostate cancer, 14 matched the inclusion criteria and were classified as follows: 5/14(36%) inaccurate reports, 3/14(21%) questionable underestimation of positive findings, originally described as unclear, 6/14(43%) negatives. Choline showed a high detection rate in BCR-prostate cancer patients with PSA >20 ng/mL. Conclusions: Although negative reports can be found in this clinical setting, in our review various disease-relevant findings were identified in more than half of the cases originally reported as negative warranting a double reading in such cases to avoid false-negative reports.

To assess the role of sentinel lymph-node biopsy (SLNB) and FDG-PET in staging and radiation treatment (RT) of anal cancer patients. This retrospective study was performed on 80 patients (male: 32, female: 48) with a median age of 60 years (39–89 years) with anal squamous cell carcinoma who were treated from March 2008 to March 2018 at the IRCCS San Raffaele Hospital. Patients without clinical evidence of inguinal LNs metastases and/or with discordance between clinical evidence and imaging features were considered for SLNB. FDG-PET was performed in 69/80 patients. Patients with negative imaging in inguinal region and negative SLNB could avoid RT on groin to spare inguinal toxicity. CTV included GTV (primary tumour and positive LNs) and pelvic ± inguinal LNs. PTV1 and PTV2 corresponded to GTV and CTV, respectively, adding 0.5 cm. RT dose was 50.4 Gy/28 fractions to PTV2 and 64.8 Gy/36 fractions to PTV1, delivered with 3DCRT (n = 24) or IMRT (n = 56), concomitant to Mitomycin-C and 5-FU chemotherapy. FDG-PET showed inguinal uptake in 21/69 patients (30%) and was negative in 48/69 patients (70%). Lymphoscintigraphy was performed in 11/21 positive patients (4 patients SLNB confirmed inguinal metastases, 6 patients false positive and 1 patient SLN not found), and in 29/48 negative patients (5/29 showed metastases, 23/29 true negative and 1 SLN not found). Sensitivity, specificity, positive and negative predictive value of FDG-PET were 62%, 79%, 40% and 82%, respectively. Median follow-up time from diagnosis was 40.3 months (range: 4.6–136.4 months): 69 patients (86%) showed a complete response, 10 patients (13%) a partial response, 1 patient (1%) a stable disease. Patients treated on groin (n = 54) versus not treated (n = 26) showed more inguinal dermatitis (G1–G2: 50% vs. 12%; G3–G4: 17% vs. 0%, p

BACKGROUND: The diagnosis of probable behavioral variant of fronto-temporal dementia (bvFTD) according to current criteria requires the imaging evidence of frontal and/or anterior temporal atrophy or hypoperfusion/hypometabolism. Different variants of this pattern of brain involvement may, however, be found in individual cases, supporting the presence of heterogeneous phenotypes. OBJECTIVE: We examined in a case-by-case approach the FDG-PET metabolic patterns of patients fulfilling clinical criteria for probable bvFTD, assessing the presence and frequency of specific FDG-PET features. MATERIALS AND METHODS: Fifty two FDG-PET scans of probable bvFTD patients were retrospectively analyzed together with clinical and neuropsychological data. Neuroimaging experts rated the FDG-PET hypometabolism maps obtained at the single-subject level with optimized voxel-based Statistical Parametric Mapping (SPM). The functional metabolic heterogeneity was further tested by hierarchical cluster analysis and principal component analysis (PCA). RESULTS: Both the SPM maps and cluster analysis identified two major variants of cerebral hypometabolism, namely the "frontal" and the "temporo-limbic", which were correlated with different cognitive profiles. Executive and language deficits were the cognitive hallmark in the "frontal" subgroup, while poor encoding and recall on long-term memory tasks was typical of the "temporo-limbic" subgroup. DISCUSSION: SPM single-subject analysis indicates distinct patterns of brain dysfunction in bvFTD, coupled with specific clinical features, suggesting different profiles of neurodegenerative vulnerability. These findings have important implications for the early diagnosis of bvFTD and for the application of the recent international consensus criteria.

Purpose To investigate the preoperative prognostic role of 18F-FDG PET/CT in patients with endometrial carcinoma (EC). Methods 18F-FDG PET/CT was performed in 57 patients for EC preoperative staging. Maximum and mean standardized uptake values (SUVmax, mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors, at different thresholds of 40%, 50%, 60% (40–50–60), were evaluated and compared with anatomopathological features. The diagnostic performance of PET-parameters (categorized by ROC analysis) in discriminating low-intermediate and high-risk disease and the prognostic role on survival (overall survival –OS; disease free survival – DFS) was evaluated. Results The categorized TLG40–50–60 were the only parameters related to FIGO stage I versus II-III-IV (p = 0.0035 for all). The cut-off values for risk stratification were 83.69, 61.81 and 41.32, respectively (sensitivity: 60.00%; specificity; 71.43% for all parameters). Pathological stage 1 (pT1) of the primary tumor was predicted by MTV60 and TLG40-50 (p = 0.0328, 0.0240, 0.0147, respectively). The optimal thresholds were 7.795, 99.55 and 77.58, respectively (sensitivity: 38.46%, 53.85% and 53.85%, respectively; specificity: 88.64%, 79.55% and 81.82%, respectively). SUVmax and SUVmean40–50–60 were the only parameters discriminating endometrioid from non-endometrioid subtype. The corresponding sensitivity was 64.86% and 62.16% for SUVmax and SUVmean 50–60 and 62.16% for SUVmean40; specificity was 70.00% for all parameters. The mean (SD) OS was 79.77% (3.34%) and the mean DFS was 77.89% (3.73%). The tumor type was the only variable significantly associated with OS (p = 0.0486). TLG50 > 77.58 cm3 was the only variable associated with a higher risk of relapse (p = 0.0472). Conclusion TLG40–50–60 and MTV60 of primary EC have prognostic value in discriminating FIGO and pathological staging. These results suggest a possible role of these parameters in predicting EC aggressiveness, thus improving the preoperative characterization of endometrial cancer.

We report a case study demonstrating the value of prone positioning in positron emission tomography (PET) of a woman with diagnosed breast cancer (BC) addressed to lumpectomy. Surgeon required (18)F-fluorodeoxiglucose ((18)F-FDG) PET study for staging and assessment of lymphnode involvement/metastasis prior to lumpectomy: a whole-body supine study and a prone acquisition of breast. Supine study revealed one lesion, while prone study revealed two lesions. Prone PET findings changed diagnosis and therapeutic intervention for patient who was subsequently subjected to quadrantectomy.

Background: Mild cognitive impairment (MCI) is a heterogeneous syndrome resulting from Alzheimer's disease (AD) as well as to non-AD and non-neurodegenerative conditions. A subset of patients with amnestic MCI (aMCI) present with an unusually long-lasting course, a slow rate of clinical neuropsychological progression, and evidence of focal involvement of medial temporal lobe structures. In the present study, we explored positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a sample of subjects with aMCI with such clinical features in order to provide in vivo evidence to improve disease characterisation in this subgroup.Methods: Thirty consecutive subjects with aMCI who had long-lasting memory impairment (more than 4 years from symptom onset) and a very slow rate of cognitive progression were included. All subjects underwent fluorodeoxyglucose-positron emission tomography (FDG-PET) metabolic imaging. A measure of cerebral amyloid load, by PET and/or CSF, was obtained in 26 of 30 subjects. The mean clinical follow-up was 58.3 ± 10.1 months.Results: No patient progressed to dementia during the follow-up. The typical AD FDG-PET pattern of temporoparietal hypometabolism was not present in any of the subjects. In contrast, a selective medial temporal lobe hypometabolism was present in all subjects, with an extension to frontolimbic regions in some subjects. PET imaging showed absent or low amyloid load in the majority of samples. The values were well below those reported in prodromal AD, and they were slightly elevated in only two subjects, consistent with the CSF β-amyloid (1–42) protein values. Notably, no amyloid load was present in the hippocampal structures.Conclusions: FDG-PET and amyloid-PET together with CSF findings questioned AD pathology as a unique neuropathological substrate in this aMCI subgroup with long-lasting disease course. The possibility of alternative pathological conditions, such as argyrophilic grain disease, primary age-related tauopathy or age-related TDP-43 proteinopathy, known to spread throughout the medial temporal lobe and limbic system structures should be considered in these patients with MCI.

Background/aims In this multicentre study in clinical settings, we assessed the accuracy of optimized procedures for FDG-PET brain metabolism and CSF classifications in predicting or excluding the conversion to Alzheimer's disease (AD) dementia and non-AD dementias. Methods We included 80 MCI subjects with neurological and neuropsychological assessments, FDG-PET scan and CSF measures at entry, all with clinical follow-up. FDG-PET data were analysed with a validated voxel-based SPM method. Resulting single-subject SPM maps were classified by five imaging experts according to the disease-specific patterns, as “typical-AD”, “atypical-AD” (i.e. posterior cortical atrophy, asymmetric logopenic AD variant, frontal-AD variant), “non-AD” (i.e. behavioural variant FTD, corticobasal degeneration, semantic variant FTD; dementia with Lewy bodies) or “negative” patterns. To perform the statistical analyses, the individual patterns were grouped either as “AD dementia vs. non-AD dementia (all diseases)” or as “FTD vs. non-FTD (all diseases)”. Aβ42, total and phosphorylated Tau CSF-levels were classified dichotomously, and using the Erlangen Score algorithm. Multivariate logistic models tested the prognostic accuracy of FDG-PET-SPM and CSF dichotomous classifications. Accuracy of Erlangen score and Erlangen Score aided by FDG-PET SPM classification was evaluated. Results The multivariate logistic model identified FDG-PET “AD” SPM classification (Expβ = 19.35, 95% C.I. 4.8–77.8, p, Highlights • Appropriate biomarkers measures improve early dementia diagnosis in MCI. • FDG-PET-SPM maps and CSF Aβ42 are the best predictors of AD dementia conversion. • FDG-PET-SPM maps accurately predict conversion to different dementia conditions. • A negative FDG-PET-SPM pattern characterizes stable or reverter MCI cases.

Objective: Postmortem studies reported significant microglia activation in association with neuronal apoptosis in Fatal Familial Insomnia (FFI), indicating a specific glial response, but negative evidence also exists. An invivo study of local immune responses over FFI natural course may contribute to the understanding of the underlying pathogenesis. Methods: We included eight presymptomatic subjects (mean±SD age:44.13±3.83years) carrying the pathogenic D178N-129met FFI mutation, one symptomatic patient (male, 45yrs. old), and nine healthy controls (HC) (mean±SD age: 44.00±11.10years.) for comparisons. 11C-(R)-PK11195 PET allowed the measurement of Translocator Protein (TSPO) overexpression, indexing microglia activation. A clustering algorithm was adopted to define subject-specific reference regions. Voxel-wise statistical analyses were performed on 11C-(R)-PK11195 binding potential (BP) images both at the group and individual level. Results: The D178N-129met/val FFI patient showed significant 11C-(R)-PK11195 BP increases in the midbrain, cerebellum, anterior thalamus, anterior cingulate cortex, orbitofrontal cortex, and anterior insula, bilaterally. Similar TSPO increases, but limited to limbic structures, were observed in four out of eight presymptomatic carriers. The only carrier with the codon 129met/val polymorphism was the only one showing an additional TSPO increase in the anterior thalamus. Interpretation: In comparison to nonprion neurodegenerative diseases, the observed lack of a diffuse brain TSPO overexpression in preclinical and the clinical FFI cases suggests the presence of a different microglia response. The involvement of limbic structures might indicate a role for microglia activation in these key pathologic regions, known to show the most significant neuronal loss and functional deafferentation in FFI.

Purpose: Hypoxia can influence response to chemo and radiotherapy in different tumours, including non-small cell lung cancer (NSCLC) and high-grade gliomas (HGG). PET/CT can non-invasively investigate hypoxia and18F-FAZA seems to be the most promising radiotracer. However, there are still controversial issues related to image analysis and data interpretation hampering the effective possibility to translate the use of this imaging modality in clinical applications. The aim of the present pictorial review is to provide insights and answers on the open issues related to the potential clinical applicability of18F-FAZA PET/CT for hypoxia delineation. Methods: From Pubmed and Scopus databases, a literature research has been performed with the following research filters for both NSCLC and HGG: (1) time frame: last 10 years; (2) language: English; (3) species: human. Applied searching keywords were “hypoxia” or “hypoxic” and “PET” and “lung cancer” for NSCLS and “hypoxia”, “PET” and “glioma” for HGG. Papers not strictly matching the imposed search filters have not been considered. Results: The literature search led to 76 papers for NSCLC, but for the purpose of the review only 10 have been considered, after double-checking and exclusion if not matching the imposed search filters. For HGG, the selected filters lead to 19 papers but only 8 have been considered for data analysis. Results on the use of18F-FAZA PET/CT in two different settings are reported in the present pictorial essay and methodological suggestions for clinical practice are presented through the description of addressed representative case reports. Conclusions: Based on literature evidence and presentation of relevant clinical case reports, issues related to18F-FAZA PET/CT in clinical settings have been addressed, providing possible solutions that may help the reliable use of this imaging method in clinical practice.

Objective: Human cancers display intra-tumor phenotypic heterogeneity and recent research has focused on developing image processing methods extracting imaging descriptors to characterize this heterogeneity. This work assesses the role of pretreatment 18F-FDG PET and DWI-MR with respect to the prognosis and prediction of neoadjuvant chemotherapy (NAC) outcomes when image features are used to characterize primitive lesions from breast cancer (BC). Materials and methods: A retrospective protocol included 38 adult women with biopsy-proven BC. Patients underwent a pre-therapy 18F-FDG PET/CT whole-body study and a pre-therapy breast multi-parametric MR study. Patients were then referred for NAC treatment and then for surgical resection, with an evaluation of the therapy response. Segmentation methods were developed in order to identify functional volumes both on 18F-FDG PET images and ADC maps. Macroscopic and histogram features were extracted from the defined functional volumes. Results: Our work demonstrates that macroscopic and histogram features from 18F-FDG PET are able to biologically characterize primitive BC, and define the prognosis. In addition, histogram features from ADC maps are able to predict the response to NAC. Conclusion: Our work suggests that pre-treatment 18F-FDG PET and pre-treatment DWI-MR provide useful complementary information for biological characterization and NAC response prediction in BC.

Background and purpose: Atypical Parkinsonian disorders (APD) frequently overlap in clinical presentations, making the differential diagnosis challenging in the early stages. The present study aimed to evaluate the accuracy of the [18F]fluoro-deoxy-glucose positron emission tomography Statistical Parametric Mapping (SPM) optimized procedure in supporting the early and differential diagnosis of APD. Methods: Seventy patients with possible APD were retrospectively included from a large clinical cohort. The included patients underwent [18F]fluoro-deoxy-glucose positron emission tomography within 3 months of the first clinical assessment and a diagnostic follow-up. An optimized SPM voxel-wise procedure was used to produce t-maps of brain hypometabolism in single subjects, which were classified by experts blinded to any clinical information. We compared the accuracy of both the first clinical diagnosis and the SPM t-map classifications with the diagnosis at follow-up as the reference standard. Results: At first diagnosis, 60% of patients were classified as possible APD (progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy) and about 40% as APD with uncertain diagnosis, providing 52% sensitivity, 97% specificity and 86% accuracy with respect to the reference standard. SPM t-map classification showed 98% sensitivity, 99% specificity and 99% accuracy, and a significant agreement with the diagnosis at follow-up (P < 0.001). Conclusions: The SPM t-map classification at entry predicted the second diagnosis at follow-up. This indicates its significantly superior role for an early identification of APD subtypes, particularly in cases of uncertain diagnosis. The use of a metabolic biomarker at entry in the instrumental work-up of APD may shorten the diagnostic time, producing benefits for treatment options and support to the patients.

PURPOSE: Gestational trophoblastic neoplasia (GTN) is a rare and aggressive tumour that is usually sensitive to chemotherapy. The usefulness of conventional imaging modalities in evaluating treatment response is limited, mainly due to the difficulty in differentiating between residual tumour tissue and necrosis. The aim of the present study was to evaluate the role of FDG PET or PET/CT in primary staging and in monitoring treatment efficacy. The effect of FDG PET and combined PET/CT on the management of patients with GTN was also evaluated comparing the differences between standard treatments based on conventional imaging and alternative treatments based on PET. METHODS: This retrospective study included 41 patients with GTN referred to San Raffaele Hospital between 2002 and 2010. All patients were studied by either PET or PET/CT in addition to conventional imaging. Of the 41 patients, 38 were evaluated for primary staging of GTN and 3 patients for chemotherapy resistance after first-line chemotherapy performed in other Institutions. To validate the PET data, PET and PET/CT findings were compared with those from conventional imaging, including transvaginal ultrasonography (TV-US) in those with uterine disease, CT and chest plain radiography in those with lung disease and whole-body CT in those with systemic metastases. Conventional imaging was considered positive for the presence of uterine disease and/or metastases when abnormal findings relating to GTN were reported. PET and PET/CT were considered concordant with conventional imaging when metabolic active disease was detected at the sites corresponding to the pathological findings on conventional imaging. In addition, in 12 of the 41 patients showing extrauterine disease, FDG PET/CT was repeated to monitor treatment efficacy, in 8 after normalization of beta human chorionic gonadotropin (?HCG) and in 4 with ?HCG resistance. In some patients, PET or PET/CT findings led to an alternative nonconventional treatment, and this was considered a change in patient management for the study analysis. RESULTS: When compared to TV-US, chest radiography and CT for staging, PET showed a concordance in 91 %, 84 % and 81 % of patients, respectively. In 8 of the 41 patients with extrauterine disease during staging, PET/CT showed a complete response to therapy after ?HCG normalization. PET and PET/CT identified the sites of persistent disease in all seven high-risk patients with ?HCG resistance, of whom four underwent second-line chemotherapy, two surgical removal of resistant disease instead of additional chemotherapy, and one surgical removal of resistant disease and second-line chemotherapy with subsequent negative ?HCG. CONCLUSION: In staging, PET cannot replace conventional imaging and does not show any information in addition to that shown by conventional imaging. The additional value of PET/CT in GTN with respect to conventional imaging is found in patients with high-risk disease. PET can identify the sites of primary and/or metastatic disease in patients with persistent high levels of ?HCG after first-line chemotherapy and may be of additional value in patient management for guiding alternative treatment.

PURPOSE: We assessed the value of [(11)C]choline positron emission tomography/computerized tomography in patients with prostate cancer in whom biochemical failure developed after radical prostatectomy but who showed no disease evidence on conventional imaging. MATERIALS AND METHODS: Considered for this study were 2,124 patients treated with radical prostatectomy who underwent [(11)C]choline positron emission tomography/computerized tomography to restage disease between December 2004 and January 2007. Study inclusion criteria were 1) previous radical prostatectomy and pelvic lymph node dissection, 2) increasing prostate specific antigen beyond 0.2 ng/ml after radical prostatectomy, 3) no lymph node disease at radical prostatectomy, 4) no evidence of metastatic disease on conventional imaging, 5) no androgen deprivation therapy and 6) no adjuvant or salvage radiotherapy. These criteria were satisfied in 109 of the 2,124 patients (5%). RESULTS: Median prostate specific antigen at imaging was 0.81 ng/ml (range 0.22 to 16.76 ml). Imaging suggested local recurrence in 4 patients (4%) and pelvic lymph node disease in 8 (7%). Scans were positive in 5%, 15% and 28% of patients with prostate specific antigen less than 1, between 1 and 2, and greater than 2 ng/ml, respectively (p

Background: We investigated the possibility that transient coronary slow-flow as assessed during coronary angiography in patients with cardiac syndrome X may impair myocardial perfusion and the effects of this phenomenon on long-term prognosis. Methods: From 50 consecutive patients with cardiac syndrome X, we prospectively recruited 16 who exhibited coronary slow-flow during angiography. The remaining 34 patients served as controls. The slow-flow phenomenon was invariably worsened by nitrates and reversed by papaverine. During slow-flow, a dose of 99m-Tc-Methoxy-isobutyl-isonitrile (MIBI) was injected in 12 patients and SPECT imaging performed 1 h later. The perfusion study was repeated after 2 days at rest and, in 9 patients, at peak exercise after 10 +/- 4 days. Patients were then regularly followed-up. Results: All 12 patients had a significant MIBI defect in the regions served by the coronary artery that showed slow-flow just prior MIBI injection. After exercise, MIBI tomograms revealed a perfusion defect in 5 out of the 9 patients who underwent stress scanning. At 14 +/- 2 years follow-up, 1 patient with slow-flow had died and 4 developed significant coronary artery disease (CAD), while all patients of the control group were alive and none had developed significant CAD. Conclusions: These results show that the slow-flow phenomenon might be the cause of transient myocardial underperfusion in patients with angina and normal coronary arteries. Apparently, this phenomenon is associated with a worse cardiac prognosis. Therefore, patients with coronary slow-flow should be carefully followed-up. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

The role of (18)FDG-PET/CT during follow-up of patients affected by Hodgkin's lymphoma (HL) in complete remission after treatment is not fully elucidated, since a wide use of F-18 fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG-PET/CT) in this setting could be limited by a relative high rate of false-positive results. Herein, we summarize a retrospective analysis of 27 patients with Hodgkin's lymphoma in complete remission after the first-line (n = 20) or salvage (n = 7) therapy receiving serial (18)FDG-PET/CT scans during follow-up. Out of 165 scans, 13 were suspected for relapse, which was confirmed in seven patients. All relapses were correctly identified by (18)FDG-PET/CT positivity, with a 100% sensitivity; false-positive rate was 46% and negative predictive value was 100%. True-positive findings were mostly associated with multiple sites, subdiaphragmatic involvement, and/or previous sites of disease. According to our results, we conclude that performing routine PET/CT scan during follow-up of those patients who are at high risk of relapse would be advisable, although caution must be adopted when interpreting PET/CT results due to the relatively high rate of false-positive findings. If FDG abnormal uptake is present at multiple nodal sites, subdiaphragmatic lymph nodes, or previous sites of disease, histological verification of PET abnormal findings is warranted.

PURPOSE: The aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI). METHODS: We evaluated the supportive role of CSF Aβ42, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression. RESULTS: Diagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer's disease and in the differential diagnosis of non-Alzheimer's disease dementias. The p-tau/Aβ42 ratio was the only CSF biomarker providing a significant classification rate for Alzheimer's disease. An Alzheimer's disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer's disease. CONCLUSION: In this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ42 ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer's disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role.

The aim of this study was to retrospectively compare the value of integrated PET/CT and separate PET plus morphological imaging studies for lesion localisation in cancer patients. Two different series of consecutive patients who had previously been treated for neoplastic disease were considered. One series consisted of 105 patients who had undergone [(18)F]fluorodeoxyglucose (FDG) PET/CT ( n=70) or [(11)C]choline PET/CT ( n=35) studies (PET/CT group). The other series comprised 105 patients who had undergone FDG PET scan ( n=70) or [(11)C]choline PET scan ( n=35) alone; in this series, PET findings were correlated with the results of morphological imaging (MI) studies, i.e. CT ( n=92) or MR imaging ( n=13) (PET+MI group). Regions of abnormal tracer uptake at PET scanning were classified as ambiguous or unambiguous depending on their precise anatomical localisation. A total of 207 and 196 lesions were found in the PET/CT and PET+MI groups, respectively. The difference in terms of number of lesions per patient detected with the two imaging protocols was not statistically significant ( P=0.718). When analysis of lesion localisation was performed, there were 7/207 (3.4%) and 30/196 (15.3%) ambiguous lesions in the PET/CT and PET+MI groups, respectively. The number of ambiguous lesions was significantly higher in the PET+MI group than in the PET/CT group (chi(2)=15.768, P

Positron emission tomography/computed tomography (PET/CT) with C-choline is an established diagnostic tool for restaging prostate cancer patients with biochemical failure after primary treatment. In the present case, C-choline PET/CT was performed in a prostate cancer patient with skeletal metastases, treated with hormonal therapy. In addition to the detection of pathologic uptake at prostate and vertebra, C-choline uptake occurred in the neck. The finding was suggestive for a parathyroid adenoma on subsequent ultrasound, then finally confirmed by parathyroid scintigraphy and histopathological analysis performed after hemithyroidectomy.

Purpose: Over the last decade, PET/CT with radiolabelled choline has been shown to be useful for restaging patients with prostate cancer (PCa) who develop biochemical failure. The limitations of most clinical studies have been poor validation of [11C]choline PET/CT-positive findings and lack of survival analysis. The aim of this study was to assess whether [11C]choline PET/CT can predict survival in hormone-naive PCa patients with biochemical failure. Methods: This retrospective study included 302 hormone-naive PCa patients treated with radical prostatectomy who underwent [11C]choline PET/CT from 1 December 2004 to 31 July 2007 because of biochemical failure (prostate-specific antigen, PSA, >0.2Âng/mL). Median PSA was 1.02Âng/mL. PCa-specific survival was estimated using Kaplan-Meier curves. Cox regression analysis was used to evaluate the association between clinicopathological variables and PCa-specific survival. The coefficients of the covariates included in the Cox regression analysis were used to develop a novel nomogram. Results: Median follow-up was 7.2Âyears (1.4–Â18.9Âyears). [11C]Choline PET/CT was positive in 101 of 302 patients (33Â%). Median PCa-specific survival after prostatectomy was 14.9Âyears (95Â% CI 9.7–Â20.1Âyears) in patients with positive [11C]choline PET/CT. Median survival was not achieved in patients with negative [11C]choline PET/CT. The 15-year PCa-specific survival probability was 42.4Â% (95Â% CI 31.7–Â53.1Â%) in patients with positive [11C]choline PET/CT and 95.5Â% (95Â% CI 93.5–Â97.5Â%) in patients with negative [11C]choline PET/CT. In multivariate analysis, [11C]choline PET/CT (hazard ratio 6.36, 95Â% CI 2.14–Â18.94, P < 0.001) and Gleason score >7 (hazard ratio 3.11, 95Â% CI 1.11–Â8.66, P = 0.030) predicted PCa-specific survival. An internally validated nomogram predicted 15-year PCa-specific survival probability with an accuracy of 80Â%. Conclusion: Positive [11C]choline PET/CT after biochemical failure predicts PCa-specific survival in hormone-naive PCa patients. Prospective studies are warranted to confirm our results before more extensive use of [11C]choline PET/CT for prognostic stratification of PCa patients.

Several studies have shown that 11C-choline PET/CT may be useful for restaging prostate cancer (PCa) patients with biochemical failure after radical prostatectomy. However, validation of 11C-choline PET/CT findings scarcely relied on histologic findings, and prognostic implications of 11C-choline PET/CT are currently unknown. The aim of this study was to assess whether 11C-choline PET/CT predicts survival in PCa patients. Methods: This retrospective study included 195 PCa patients treated with radical prostatectomy who underwent 11C-choline PET/CT from December 1, 2004, to July 31, 2007, due to biochemical failure (prostate-specific antigen > 0.2 mg/mL) during androgen-deprivation therapy. PCa-specific survival was computed as the interval from radical prostatectomy to PCa-specific death. Results: The median interval after radical prostatectomy was 8.9 y (95% confidence interval [CI], 1.7-18.9 y). The median follow-up after 11C-choline PET/CT was 4.5 y (95% CI, 0.4-8.5 y). 11C-choline PET/CT results were positive in 57% of patients. The median PCa-specific survival was 16.4 y (95% CI, 14.0-18.8 y) in patients with negative 11C-choline PET/CT results and 11.2 y (95% CI, 9.8-12.6 y) in patients with positive 11C-choline PET/CT results (log-rank: x2 = 19.3, P < 0001). At multivariate analysis, statistical significance was obtained for 11C-choline PET/CT (hazard ratio, 2.53; 95% CI, 1.41-4.53; P = 0.002), prostate-specific antigen (hazard ratio, 1.03; 95% CI, 1.00-1.05; P = 0.037), and Gleason score (>7: hazard ratio, 2.49; 95% CI, 1.25-4.95; P = 0.009). Patients with pathologic 11C-choline uptake in the prostatic bed or in pelvic or retroperitoneal lymph nodes had longer PCaspecific survival (median, 12.1 y; 95% CI, 10.5-13.7 y) in comparison to patients with pathologic tracer uptake in the skeleton (median, 9.9 y; 95% CI, 6.8-13.1 y) (log-rank: x2 = 6.5, P < 0.010). Two internally validated nomograms predicted 10- and 15-y PCa-specific survival probability with an accuracy of 76% and 74%, respectively. In an ancillary analysis, we also showed that 11C-choline PET/CT predicts PCa-specific survival after PET/CT, with similar statistical power. Conclusion: 11C-choline PET/CT predicts PCa-specific survival in PCa patients treated with radical prostatectomy who develop biochemical failure during androgen-deprivation therapy. If independent or multicenter confirmation of these findings is obtained, 11Ccholine PET/CT might be more widely used in the follow-up of PCa patients for tailoring salvage therapy. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Aim The prognostic utility of myocardial perfusion scintigraphy (MPS) in patients with angiographically normal coronary arteries has not been evaluated yet. Our aim was to determine the prognostic role of positive MPS in patients with angina, positive exercise test and smooth coronary arteries (syndrome X). Methods A total of 156 patients with angina, positive exercise test, positive MPS and normal coronary arteries and 172 patients with angina and positive exercise test who had negative MPS were selected for study. The primary endpoint was combined all-cause mortality and hospitalizations for cardiac causes. The secondary endpoint was hospitalization for cardiac causes. Results Kaplan–Meier analysis showed a greater ( p =0.001) incidence of the primary endpoint in patients with positive MPS, compared to those with negative MPS. Additionally, Kaplan–Meier analysis for cardiovascular hospitalization showed a significant difference ( p =0.003) between the two groups. Cox regression analysis, adjusted for age, sex, BMI and antianginal therapy confirmed a significant risk increase for patients with positive MPS, with a hazard ratio (HR)=3.20 (CI 95%: 1.14–9.02; p =0.028). Cox analysis for cardiovascular hospitalization also showed a significant risk increase for patients with positive MPS (HR=3.19; CI 95%: 1.13–9.00; p =0.03). Finally, Cox analysis showed that patients with positive MPS tend to have a higher risk to remain symptomatic in the follow-up period (HR=1.614; CI 95%: 0.999–2.607; p =0.51). Conclusions This study shows that inducible myocardial hypoperfusion at MPS in patients with syndrome X could discriminate patients with a more severe prognosis, especially in terms of further hospitalization and symptomatic burden.

Purpose: The aim of this study was to evaluate the predictive role of pre-therapy fluorodeoxyglucose (FDG) uptake parameters of primary tumour in head and neck cancer (HNC) patients undergoing intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) on FDG-positive volume - positron emission tomography (PET) gross tumour volume (PET-GTV). Methods: This retrospective study included 19 patients (15 men and 4 women, mean age 59.2 years, range 23-81 years) diagnosed with HNC between 2005 and 2011. Of 19 patients, 15 (79 %) had stage III-IV. All patients underwent FDG PET/CT before treatment. Metabolic indexes of primary tumour, including metabolic tumour volume (MTV), maximum and mean standardized uptake value (SUVmax, SUVmean) and total lesion glycolysis (TLG) were considered. Partial volume effect correction (PVC) was performed for SUVmean and TLG estimation. Correlations between PET/CT parameters and 2-year disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were assessed. Median patient follow-up was 19.2 months (range 4-24 months). Results: MTV, TLG and PVC-TLG predicting patients' outcome with respect to all the considered local and distant disease control endpoints (LRFS, DMFS and DFS) were 32.4 cc, 469.8 g and 547.3 g, respectively. SUVmean and PVC-SUVmean cut-off values predictive of LRFS and DFS were 10.8 and 13.3, respectively. PVC was able to compensate errors up to 25 % in the primary HNC tumour uptake. Moreover, PVC enhanced the statistical significance of the results. Conclusion: FDG PET/CT uptake parameters are predictors of patients' outcome and can potentially identify patients with higher risk of treatment failure that could benefit from more aggressive approaches. Application of PVC is recommended for accurate measurement of PET parameters.

We propose a renal imaging agent, the 99m Tc complex of the bidentate- N ,S chelate N -(mercaptoacetyl) glycine ( 99m Tc-2GAM), with the imaging characteristics of 99m Tc-DMSA but a faster kidney uptake; chemical evidence supports the formulation of 99m Tc-2GAM as [Tc V (O)(GAM) 2 ] − . After biodistribution and toxicity studies in animals, 99m Tc-2GAM was evaluated in five normal volunteers. 99m Tc-2GAM is rapidly cleared from the blood (t12 = 9 min) and 50% of the ID is excreted in the urine in the first 2 h. Dynamic data show a rapid renal uptake that increases up to 1 h with no significant wash-out between 1 and 8 h. The uptake in each kidney ranges from 11.3% to 20.7% ID. Low, stable liver uptake is observed. No significant activity is detected in other organs. We showed no differences between 99m Tc-2GAM and 99m Tc-DMSA compared in three patients with unilateral kidney disease. We conclude that 99m Tc-2GAM has good practical and dosimetric features for renal imaging.

Several case reports describing the coexistence of sarcoidosis and malignancy have been published. Therefore, sarcoidosis should always be considered as a differential diagnosis when a cancer patient develops lymphadenopathy. Positron-emission tomography (PET) 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) combined with computed tomography (CT) is widely used for cancer staging and surveillance because it permits localization of metabolically active malignant tissue. PET/CT or CT findings in patients with suspected cancer recurrence can be used to guide early and aggressive therapy. However, benign hypermetabolic lymphadenopathy can mimic malignant lymphadenopathy, both on a conventional CT scan and on PET/CT. Thus, it is important to obtain a histological diagnosis before initiating antineoplastic therapy based on imaging findings. Four cases of patients affected by gynaecological malignancies and coexisting sarcoidosis are reported in this study. Furthermore, the clinical relevance of making a differential diagnosis between gynaecological cancer recurrence and granulomatous disorder is given specific mention.

PURPOSE: The effectiveness of salvage therapy in prostate cancer is greater for low prostate specific antigen values. Therefore, early detection of tumor recurrence is warranted. [(11)C]choline positron emission tomography/computerized tomography has the potential of early restaging of prostate cancer with low prostate specific antigen, but the selection of patients at high risk for positive [(11)C]choline positron emission tomography/computerized tomography is desirable to optimize salvage therapy. MATERIALS AND METHODS: This retrospective study included 75 patients with prostate cancer with an increasing prostate specific antigen less than 1.5 ng/ml after radical prostatectomy who never received antiandrogen deprivation therapy or salvage radiotherapy who underwent [(11)C]choline positron emission tomography/computerized tomography for the restaging of disease. Binary logistic regression was used to assess predictive factors of positive [(11)C]choline positron emission tomography/computerized tomography. Included variables were trigger prostate specific antigen, prostate specific antigen doubling time, age, pathological stage and Gleason score. RESULTS: Median prostate specific antigen was 0.61 ng/ml. [(11)C]choline positron emission tomography/computerized tomography was positive in 16 of 75 patients (21%). On univariate analysis prostate specific antigen doubling time less than 6 months was the only factor significantly associated with an increased risk of positive [(11)C]choline positron emission tomography/computerized tomography (OR 7.77, 95% CI 2.34-25.80, p = 0.001). In patients with prostate specific antigen doubling time less than 6 months, the positive detection rate of [(11)C]choline positron emission tomography/computerized tomography increased to 50%. CONCLUSIONS: In patients with prostate cancer with biochemical failure after radical prostatectomy and prostate specific antigen less than 1.5 ng/ml, prostate specific antigen doubling time less than 6 months predicts positive [(11)C]choline positron emission tomography/computerized tomography. In these patients [(11)C]choline positron emission tomography/computerized tomography may reduce by 50% the number in whom salvage therapy is initiated empirically without knowing the disease location.

Cancer vaccines have recently been shown to induce some clinical benefits. The relationship between clinical activity and anti-vaccine T cell responses is somewhat controversial. Indeed, in many trials it has been documented that the induction of vaccine-specific T cells exceeds the clinical responses observed. Here, we evaluate immunological and clinical responses in 23 MAGE-A3+ melanoma patients treated with autologous lymphocytes genetically engineered to express the tumor antigen MAGE-A3 and the viral gene product thymidine kinase of the herpes simplex virus (HSV-TK). HSV-TK was used as safety system in case of adverse events and as tracer antigen to monitor the immune competence of treated patients. The increase of anti-TK and anti-MAGE-A3 T-cells after vaccination was observed in 90 and 27% of patients, respectively. Among 19 patients with measurable disease, we observed a disease control rate of 26.3%, with one objective clinical response, and four durable, stable diseases. Three patients out of five with no evidence of disease (NED) at the time of vaccination remained NED after 73+, 70+ and 50+ months. Notably, we report that only patients experiencing MAGE-A3-specific immune responses showed a clinical benefit. Additionally, we report that responder and non-responder patients activate and expand T cells against the tracer antigen TK in a similar way, suggesting that local rather than systemic immune suppression might be involved in limiting clinically relevant antitumor immune responses. OI bregni, marco/0000-0002-3789-1199

Purpose: We previously showed that prostate-specific antigen (PSA) doubling time (PSADT) is a significant predictor of C-11 choline positron emission tomography/computed tomography (PET/CT) findings in prostate cancer (PCa) patients. This study compared PSA velocity (PSAV) and PSADT to predict C-11 choline PET/CT findings. Materials and Methods: PSAV and PSADT were retrospectively calculated in 170 PCa patients with biochemical failure after radical prostatectomy, who underwent C-11 choline PET/CT for restaging of disease. Results: Median PSA was 1.25 ng/mL (range: 0.23-48.6 ng/mL), and median PSAV was 0.99 ng/mL/y (range: 0.11-98.9 ng/mL/y). Patients with positive C-11 choline PET/CT (n = 75) had significantly (P < 0.05) higher PSAV than patients with negative C-11 choline PET/CT (n = 95) (6.93 +/- 13.08 vs. 1.23 +/- 2.03 ng/mL/y). The percent of patients with positive C-11 choline PET/CT was 21% for PSAV 2 ng/mL/y. The quality of fitting (r(2)) of PSA values according to the exponential function (PSADT) was significantly (P < 0.05) better than the quality of fitting according to the linear function (PSAV) in the entire sample and in all anatomic regions. At multivariate analysis, trigger PSA, PSADT but not PSAV obtained the statistical significance (P < 0.05). Conclusions: PSAV can be used to stratify the risk of positive C-11 choline PET/CT in PCa patients with biochemical failure. Patients with PSAV >1 ng/mL/y should be selected to increase the positive detection rate of C-11 choline PET/CT. The greater statistical power of PSADT compared with PSAV could be related to the better capability of fitting time-dependent changes in PSA values, thereby better reflecting the natural growth of recurrent PCa. Purpose: We previously showed that prostate-specific antigen (PSA) doubling time (PSADT) is a significant predictor of C-11 choline positron emission tomography/computed tomography (PET/CT) findings in prostate cancer (PCa) patients. This study compared PSA velocity (PSAV) and PSADT to predict C-11 choline PET/CT findings. Materials and Methods: PSAV and PSADT were retrospectively calculated in 170 PCa patients with biochemical failure after radical prostatectomy, who underwent C-11 choline PET/CT for restaging of disease. Results: Median PSA was 1.25 ng/mL (range: 0.23-48.6 ng/mL), and median PSAV was 0.99 ng/mL/y (range: 0.11-98.9 ng/mL/y). Patients with positive C-11 choline PET/CT (n = 75) had significantly (P < 0.05) higher PSAV than patients with negative C-11 choline PET/CT (n = 95) (6.93 +/- 13.08 vs. 1.23 +/- 2.03 ng/mL/y). The percent of patients with positive C-11 choline PET/CT was 21% for PSAV 2 ng/mL/y. The quality of fitting (r(2)) of PSA values according to the exponential function (PSADT) was significantly (P < 0.05) better than the quality of fitting according to the linear function (PSAV) in the entire sample and in all anatomic regions. At multivariate analysis, trigger PSA, PSADT but not PSAV obtained the statistical significance (P < 0.05). Conclusions: PSAV can be used to stratify the risk of positive C-11 choline PET/CT in PCa patients with biochemical failure. Patients with PSAV >1 ng/mL/y should be selected to increase the positive detection rate of C-11 choline PET/CT. The greater statistical power of PSADT compared with PSAV could be related to the better capability of fitting time-dependent changes in PSA values, thereby better reflecting the natural growth of recurrent PCa.

18F-FDG-PET/CT is widely employed to evaluate lymphoma patients. False positive results are quite frequent, generally due to active phase of inflammation. We describe an unusual PET/CT presentation of a sarcoid-like reaction (SLR) in a patient monitored for Hodgkin Lymphoma characterized by an intense uptake in lymph nodes and multiple bone foci in a PET/CT study. The final diagnosis was obtained by biopsy. This study draws attention to the fact that multifocal bone marrow uptakes due to a sarcoideal reaction may be a possible cause of false positive results in 18F-FDG-PET/CT studies in oncology patients. © 2012 Elsevier España, S.L. and SEMNIM

PURPOSE: The aim of this study was to evaluate the clinical usefulness of [(11)C]choline positron emission tomography (PET)/CT in comparison with bone scintigraphy (BS) in detecting bone metastases (BM) of patients with biochemical progression after radical treatment for prostate cancer (PCa). METHODS: Seventy-eight consecutive patients with biochemical progression of PCa (mean prostate-specific antigen 21.1 ng/ml, range 0.2-500.0 ng/ml) referred for both [(11)C]choline PET/CT and BS for restaging purposes were retrospectively analysed. The diagnostic accuracy of [(11)C]choline PET/CT and BS was assessed by using morphological imaging and/or follow-up as standards of reference. As equivocal findings were found, the accuracy analysis was performed twice, once including them as positive and once as negative. A separate analysis was also performed in hormone-resistant patients and data compared with those of patients who did not receive anti-androgenic treatment. RESULTS: Equivocal findings occurred in 1 of 78 (1%) cases in [(11)C]choline PET/CT and in 21 of 78 (27%) cases in BS. Depending on their attribution as either positive or negative, the ranges of sensitivity, specificity, positive predictive value, negative predictive value and accuracy for [(11)C]choline PET/CT were 89-89%, 98-100%, 96-100%, 94-96% and 95-96%, respectively. For BS they were 100-70%, 75-100%, 68--100%, 100-86% and 83-90%, respectively. Concordant findings between [(11)C]choline PET/CT and BS occurred in 55 of 78 (71%) cases. The accuracy of [(11)C]choline PET/CT did not significantly (p = 0.30) differ between hormone-resistant patients (97%) and those who did not receive anti-androgenic treatment (95%). CONCLUSION: In clinical practice, [(11)C]choline PET/CT may not replace BS because of its lower sensitivity. However, for its high specificity, [(11)C]choline PET/CT positive findings may accurately predict the presence of BM. Equivocal findings are more frequent in BS than [(11)C]choline PET/CT.

The present chapter is focused on the role of positron emission tomography/computed tomography (PET/CT) and [11C]-labelled Choline ([11C]Choline) for the management of prostate cancer patients for radiation therapy planning. Although still a matter of debate. PET/CT with [11C]Choline is not routinely recommended for selecting patients for prostate cancer primary radiation treatment. However, due to its high accuracy in detecting and localizing recurrences when a biochemical failure occurs, [11C]Choline PET/CT may play a role in the re-staging phase to distinguish patients with local versus distant relapse, thus influencing patient management (curative versus palliative therapy). Limited data are currently available on the role of [11C]Choline PET/CT in target volume selection and delineation. According to available literature, [11C]Choline PET/CT is not clinically recommendable to plan target volume both for primary prostate treatment and for local recurrence. Nevertheless, promising data suggested a potential role of [11C]Choline PET/CT as an image guide tool for the irradiation of prostate cancer relapse. (C) 2010 European Society for Therapeutic Radiology and Oncology and European Association of Nuclear Medicine. Published by Elsevier Ireland Ltd. All rights reserved. 96 (2010) 347-350

Previous studies have shown that the positive detection rate of [C-11]choline positron emission tomography/computed tomography (PET/CT) depends on prostate-specific antigen (PSA) plasma levels. This study compared PSA levels and PSA doubling time (PSADT) to predict [C-11]choline PET/CT findings. PSADT was retrospectively calculated in 170 prostate cancer (PCa) patients with biochemical failure after radical prostatectomy who underwent [C-11]choline PET/CT. PSADT was calculated as PSADT = ln2/m, where m is the slope of the linear regression line of the natural log of PSA values. At least three PSA measurements were used (median: 4; range: 3-16), separated by at least 3 months, each with a minimum increase of 0.20 ng/ml. PET/CT findings were validated using criteria based on histological analysis and clinical and imaging data. Statistical analysis was performed using the t test, chi-square test, analysis of variance and binary logistic regression. Regression-based coefficients were used to develop a nomogram predicting the probability of positive [C-11]choline PET/CT and 200 bootstrap resamples were used for internal validation. The median PSA was 1.25 ng/ml (range: 0.23-48.6 ng/ml), and the median PSADT was 7.0 months (range: 0.97-45.3 months). [C-11]choline PET/CT was positive in 75 of 170 patients (44%). PET/CT findings were validated using histological criteria (11%) and clinical and imaging criteria (89%). The overall accuracy of [C-11]choline PET/CT was 88%. Multivariate logistic regression showed that high PSA and short PSADT were significant (p < 0.05) predictors of positive [C-11]choline PET/CT [PSA: odds ratio (OR) = 1.43; 95% confidence interval (CI): 1.15-1.78; PSADT: OR = 1.12; 95% CI: 1.04-1.21]. The percentage of patients with positive [C-11]choline PET/CT was 27% for PSADT > 6 months, 61% for PSADT between 3 and 6 months and 81% for PSADT < 3 months. The percentage of patients who displayed pathological [C-11]choline uptake in the skeleton significantly increased (p < 0.05) from 3% for PSADT > 6 months to 52% for PSADT < 3 months. Conversely, patients who displayed pathological [C-11]choline uptake in the prostatectomy bed were 0% for PSADT < 3 months and 17% for PSADT > 6 months (p < 0.05). A nomogram based on age, PSA, PSADT, time to trigger PSA, Gleason score, pathological stage and androgen deprivation therapy demonstrated bootstrap-corrected predictive accuracy of 81%. Like PSA, PSADT is an independent predictor of [C-11]choline PET/CT. [C-11]choline PET/CT is very sensitive to PCa tumour growth, as reflected by PSA kinetics. PSADT should be taken into account by physicians when referring PCa patients for [C-11]choline PET/CT. Previous studies have shown that the positive detection rate of [C-11]choline positron emission tomography/computed tomography (PET/CT) depends on prostate-specific antigen (PSA) plasma levels. This study compared PSA levels and PSA doubling time (PSADT) to predict [C-11]choline PET/CT findings. PSADT was retrospectively calculated in 170 prostate cancer (PCa) patients with biochemical failure after radical prostatectomy who underwent [C-11]choline PET/CT. PSADT was calculated as PSADT = ln2/m, where m is the slope of the linear regression line of the natural log of PSA values. At least three PSA measurements were used (median: 4; range: 3-16), separated by at least 3 months, each with a minimum increase of 0.20 ng/ml. PET/CT findings were validated using criteria based on histological analysis and clinical and imaging data. Statistical analysis was performed using the t test, chi-square test, analysis of variance and binary logistic regression. Regression-based coefficients were used to develop a nomogram predicting the probability of positive [C-11]choline PET/CT and 200 bootstrap resamples were used for internal validation. The median PSA was 1.25 ng/ml (range: 0.23-48.6 ng/ml), and the median PSADT was 7.0 months (range: 0.97-45.3 months). [C-11]choline PET/CT was positive in 75 of 170 patients (44%). PET/CT findings were validated using histological criteria (11%) and clinical and imaging criteria (89%). The overall accuracy of [C-11]choline PET/CT was 88%. Multivariate logistic regression showed that high PSA and short PSADT were significant (p < 0.05) predictors of positive [C-11]choline PET/CT [PSA: odds ratio (OR) = 1.43; 95% confidence interval (CI): 1.15-1.78; PSADT: OR = 1.12; 95% CI: 1.04-1.21]. The percentage of patients with positive [C-11]choline PET/CT was 27% for PSADT > 6 months, 61% for PSADT between 3 and 6 months and 81% for PSADT < 3 months. The percentage of patients who displayed pathological [C-11]choline uptake in the skeleton significantly increased (p < 0.05) from 3% for PSADT > 6 months to 52% for PSADT < 3 months. Conversely, patients who displayed pathological [C-11]choline uptake in the prostatectomy bed were 0% for PSADT < 3 months and 17% for PSADT > 6 months (p < 0.05). A nomogram based on age, PSA, PSADT, time to trigger PSA, Gleason score, pathological stage and androgen deprivation therapy demonstrated bootstrap-corrected predictive accuracy of 81%. Like PSA, PSADT is an independent predictor of [C-11]choline PET/CT. [C-11]choline PET/CT is very sensitive to PCa tumour growth, as reflected by PSA kinetics. PSADT should be taken into account by physicians when referring PCa patients for [C-11]choline PET/CT.

Background: Several guidelines have indicated that in patients with well-differentiated or moderately well-differentiated prostate cancer (PCa), a staging bone scan may be omitted. However, the guidelines recommendations have not yet been externally validated. Objective: The aim of the study was to externally validate the available guidelines regarding the need for a staging bone scan in patients with newly diagnosed PCa. Moreover, we developed a novel risk stratification tool aimed at improving the accuracy of these guidelines. Design, setting, and participants: The study included 853 consecutive patients diagnosed with PCa between January 2003 and June 2008 at a single centre. All patients underwent bone scan using technetium Tc 99m methylene diphosphonate at diagnosis. Measurements: The area under the curve (AUC) of the criteria suggested by the guidelines (European Association of Urology, American Urological Association, National Comprehensive Cancer Network, and American Joint Committee on Cancer) to perform a baseline bone scan was assessed and compared with the accuracy of a classification and regression tree (CART) including prostate-specific antigen (PSA), clinical stage, and biopsy Gleason sum as covariates. Results and limitations: The AUC of the guidelines ranged between 79.7% and 82.6%. However, the novel CART model, which stratified patients into low risk (biopsy Gleason 10 ng/ml), and high risk (biopsy Gleason > 7) was significantly more accurate (AUC: 88.0%) than all the guidelines (all p 7 or with a PSA > 10 ng/ml and palpable disease (cT2/T3) prior to treatment. However, before recommending its use in clinical practice, our model needs to be externally validated. (c) 2009 European Association of Urology. Published by Elsevier B. V. All rights reserved. Background: Several guidelines have indicated that in patients with well-differentiated or moderately well-differentiated prostate cancer (PCa), a staging bone scan may be omitted. However, the guidelines recommendations have not yet been externally validated. Objective: The aim of the study was to externally validate the available guidelines regarding the need for a staging bone scan in patients with newly diagnosed PCa. Moreover, we developed a novel risk stratification tool aimed at improving the accuracy of these guidelines. Design, setting, and participants: The study included 853 consecutive patients diagnosed with PCa between January 2003 and June 2008 at a single centre. All patients underwent bone scan using technetium Tc 99m methylene diphosphonate at diagnosis. Measurements: The area under the curve (AUC) of the criteria suggested by the guidelines (European Association of Urology, American Urological Association, National Comprehensive Cancer Network, and American Joint Committee on Cancer) to perform a baseline bone scan was assessed and compared with the accuracy of a classification and regression tree (CART) including prostate-specific antigen (PSA), clinical stage, and biopsy Gleason sum as covariates. Results and limitations: The AUC of the guidelines ranged between 79.7% and 82.6%. However, the novel CART model, which stratified patients into low risk (biopsy Gleason 10 ng/ml), and high risk (biopsy Gleason > 7) was significantly more accurate (AUC: 88.0%) than all the guidelines (all p 7 or with a PSA > 10 ng/ml and palpable disease (cT2/T3) prior to treatment. However, before recommending its use in clinical practice, our model needs to be externally validated. (c) 2009 European Association of Urology. Published by Elsevier B. V. All rights reserved.

[11C]choline positron emission tomograhy can be useful to detect metastatic disease and to localize isolated lymph node relapse after primary treatment in case of prostate-specific antigen failure. In case of lymph node failure in prostate cancer patients, surgery or radiotherapy can be proposed with a curative intent. Some reports have suggested that radiotherapy could have a role in local control of oligometastatic lymph node disease. This is the first reported case of [11C]choline positron emission tomography-guided helical tomotherapy concomitant with estramustine for the treatment of pelvic-recurrent prostate cancer. At 24 months after the end of helical tomotherapy, prostate-specific antigen was undetectable and no late toxicities were recorded. A disease-free survival of 24 months, in the absence of any type of systemic therapy, is uncommon in metastatic prostate cancer. The therapeutic approach of the case report is discussed and a literature review on the issue is presented.