Dopaminergic dysfunction in the left putamen of patients with major depressive disorder.

INTRODUCTION: Dopaminergic transmission impairment has been identified as one of the main neurobiological correlates of both depression and clinical symptoms commonly associated with its spectrum such as anhedonia and psychomotor retardation. OBJECTIVES: We examined the relationship between dopaminergic deficit in the striatum, as measured by 123I-FP-CIT SPECT imaging, and specific psychopathological dimensions in patients with major depressive disorder. METHODS: To our knowledge this is the first study with a sample of >120 subjects. After check for inclusion and exclusion criteria, 121 (67 females, 54 males) patients were chosen retrospectively from an extensive 1106 patients database of 123I-FP-CIT SPECT scans obtained at the Nuclear Medicine Unit of Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome. These individuals had undergone striatal dopamine transporter (DAT) assessments based on the recommendation of their referring clinicians, who were either neurologists or psychiatrists. At the time of SPECT imaging, each participant underwent psychiatric and psychometric evaluations. We used the following psychometric scales: Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Snaith Hamilton Pleasure Scale, and Depression Retardation Rating Scale. RESULTS: We found a negative correlation between levels of depression (p = 0.007), anxiety (p = 0.035), anhedonia (p = 0.028) and psychomotor retardation (p = 0.014) and DAT availability in the left putamen. We further stratified the sample and found that DAT availability in the left putamen was lower in seriously depressed patients (p = 0.027) and in patients with significant psychomotor retardation (p = 0.048). CONCLUSION: To our knowledge this is the first study to have such a high number of sample. Our study reveals a pivotal role of dopaminergic dysfunction in patients with major depressive disorder. Elevated levels of depression, anxiety, anhedonia, and psychomotor retardation appear to be associated with reduced DAT availability specifically in the left putamen.

Lung perfusion assessment in children with long-COVID: A pilot study.

BACKGROUND: There is increasing evidence that chronic endotheliopathy can play a role in patients with Post-Covid Condition (PCC, or Long Covid) by affecting peripheral vascularization. This pilot study aimed at assessing lung perfusion in children with Long-COVID with 99m Tc-MAA SPECT/CT. MATERIALS AND METHODS: lung 99m Tc-MAA SPECT/CT was performed in children with Long-COVID and a pathological cardiopulmonary exercise testing (CPET). Intravenous injections were performed on patients in the supine position immediately before the planar scan according to the EANM guidelines for lung scintigraphy in children, followed by lung SPECT/CT acquisition. Reconstructed studies were visually analyzed. RESULTS: Clinical and biochemical data were collected during acute infection and follow-up in 14 children (6 females, mean age: 12.6 years) fulfilling Long-COVID diagnostic criteria and complaining of chronic fatigue and postexertional malaise after mild efforts, documented by CPET. Imaging results were compared with clinical scenarios during acute infection and follow-up. Six out of 14 (42.8%) children showed perfusion defects on 99m Tc-MAA SPECT/CT scan, without morphological alterations on coregistered CT. CONCLUSIONS: This pilot investigation confirmed previous data suggesting that a small subgroup of children can develop lung perfusion defects after severe acute respiratory syndrome coronavirus 2 infection. Larger cohort studies are needed to confirm these preliminary results, providing also a better understanding of which children may deserve this test and how to manage those with lung perfusion defects.

PSMA Radioligand Uptake as a Biomarker of Neoangiogenesis in Solid Tumours: Diagnostic or Theragnostic Factor?

Due to its overexpression on the surface of prostate cancer cells, prostate-specific membrane antigen (PSMA) is a relatively novel effective target for molecular imaging and radioligand therapy (RLT) in prostate cancer. Recent studies reported that PSMA is expressed in the neovasculature of various types of cancer and regulates tumour cell invasion as well as tumour angiogenesis. Several authors explored the role of diagnostic and therapeutic PSMA radioligands in various malignancies. In this narrative review, we describe the current status of the literature on PSMA radioligands' application in solid tumours other than prostate cancer to explore their potential role as diagnostic or therapeutic agents, with particular regard to the relevance of PSMA radioligand uptake as neoangiogenetic biomarker. Hence, a comprehensive review of the literature was performed to find relevant articles on the applications of PSMA radioligands in non-prostate solid tumours. Data on the general, methodological and clinical aspects of all included studies were collected. Forty full-text papers were selected for final review, 8 of which explored PSMA radioligand PET/CT performances in gliomas, 3 in salivary gland malignancies, 6 in thyroid cancer, 2 in breast cancer, 16 in renal cell carcinoma and 5 in hepatocellular carcinoma. In the included studies, PSMA radioligand PET showed promising performance in patients with non-prostate solid tumours. Further studies are needed to better define its potential role in oncological patients management, especially in those undergoing antineoangiogenic therapies, and to assess the efficacy of PSMA-RLT in this clinical context.

18F-Fluoroethylcholine PET/CT Radiomic Analysis for Newly Diagnosed Prostate Cancer Patients: A Monocentric Study.

AIM: The aim of this study is to assess whether there are some correlations between radiomics and baseline clinical-biological data of prostate cancer (PC) patients using Fluorine-18 Fluoroethylcholine (18F-FECh) PET/CT. METHODS: Digital rectal examination results (DRE), Prostate-Specific Antigen (PSA) serum levels, and bioptical-Gleason Score (GS) were retrospectively collected in newly diagnosed PC patients and considered as outcomes of PC. Thereafter, Volumes of interest (VOI) encompassing the prostate of each patient were drawn to extract conventional and radiomic PET features. Radiomic bivariate models were set up using the most statistically relevant features and then trained/tested with a cross-fold validation test. The best bivariate models were expressed by mean and standard deviation to the normal area under the receiver operating characteristic curves (mAUC, sdAUC). RESULTS: Semiquantitative and radiomic analyses were performed on 67 consecutive patients. tSUVmean and tSkewness were significant DRE predictors at univariate analysis (OR 1.52 [1.01; 2.29], p = 0.047; OR 0.21 [0.07; 0.65], p = 0.007, respectively); moreover, tKurtosis was an independent DRE predictor at multivariate analysis (OR 0.64 [0.42; 0.96], p = 0.03) Among the most relevant bivariate models, szm_2.5D.z.entr + cm.clust.tend was a predictor of PSA levels (mAUC 0.83 ± 0.19); stat.kurt + stat.entropy predicted DRE (mAUC 0.79 ± 0.10); cm.info.corr.1 + szm_2.5D.szhge predicted GS (mAUC 0.78 ± 0.16). CONCLUSIONS: tSUVmean, tSkewness, and tKurtosis were predictors of DRE results only, while none of the PET parameters predicted PSA or GS significantly; 18F-FECh PET/CT radiomic models should be tested in larger cohort studies of newly diagnosed PC patients.

Is PET/CT Able to Predict Histology in Thymic Epithelial Tumours? A Narrative Review.

BACKGROUND: The usefulness of 18FDG PET/CT scan in the evaluation of thymic epithelial tumours (TETs) has been reported by several authors, but data are still limited and its application in clinical practice is far from being defined. METHODS: We performed a narrative review of pertinent literature in order to clarify the role of 18FDG PET/CT in the prediction of TET histology and to discuss clinical implications and future perspectives. RESULTS: There is only little evidence that 18FDG PET/CT scan may distinguish thymic hyperplasia from thymic epithelial tumours. On the other hand, it seems to discriminate well thymomas from carcinomas and, even more, to predict the grade of malignancy (WHO classes). To this end, SUVmax and other PET variables (i.e., the ratio between SUVmax and tumour dimensions) have been adopted, with good results. Finally, however promising, the future of PET/CT and theranostics in TETs is far from being defined; more robust analysis of imaging texture on thymic neoplasms, as well as new exploratory studies with "stromal PET tracers," are ongoing. CONCLUSIONS: PET may play a role in predicting histology in TETs and help physicians in the management of these insidious malignancies.

The impact of the COVID-19 pandemic on oncological disease extent at FDG PET/CT staging: the ONCOVIPET study.

PURPOSE: To investigate whether the COVID-19 pandemic and national lockdown had an impact on the extent of cancer disease at FDG PET/CT staging as surrogate marker. METHODS: Retrospective observational study including cancer patients submitted to FDG PET/CT staging from June 1 to October 31, 2020, and June 1 to October 31, 2019, respectively. Data regarding primary tumour, nodal (N) status and number of involved nodal stations, and presence and number of distant metastases (M) were collected. Each scan was classified in limited vs advanced status. Data were aggregated across the study population and tumour type. Bi-weekly frequencies of the observed events were analysed. RESULTS: Six hundred eleven patients were included (240 in 2019 vs 371 in 2020, respectively). A significant increase of advanced disease patients (rate 1.56, P < 0.001), N + or M + patients (rate 1.84 and 2.09, respectively, P < 0.001), and patients with a greater number of involved N stations or M (rate 2.01 and 2.06, respectively, P < 0.001) were found in 2020 compared with data of 2019. Analysis by tumour type showed a significant increase of advanced disease in lymphoma and lung cancer in 2020 compared with 2019 (P < 0.001). In addition, a significant increase of nodal involvement was found in lung, gastro-intestinal, and breast cancers, as well as in lymphoma patients (P < 0.02). A significant increase of distant metastases was found in lung cancers (P = 0.002). CONCLUSION: Cancer patients with advanced disease at FDG PET/CT staging increased in 2020 compared with 2019, following the national lockdown due to the COVID-19 pandemic, 1.5-fold with a significant increase of patients with N or M involvement. Targeted health interventions are needed to mitigate the effects of the pandemic on patient outcome.

Current Roles of PET/CT in Thymic Epithelial Tumours: Which Evidences and Which Prospects? A Pictorial Review.

BACKGROUND: The use of 18F FDG PET/CT scan in thymic epithelial tumours (TET) has been reported in the last two decades, but its application in different clinical settings has not been clearly defined. METHODS: We performed a pictorial review of pertinent literature to describe different roles and applications of this imaging tool to manage TET patients. Finally, we summarized future prospects and potential innovative applications of PET in these neoplasms. RESULTS: 18FFDG PET/CT scan may be of help to distinguish thymic hyperplasia from thymic epithelial tumours but evidences are almost weak. On the contrary, this imaging tool seems to be very performant to predict the grade of malignancy, to a lesser extent pathological response after induction therapy, Masaoka Koga stage of disease and long-term prognosis. Several other radiotracers have some application in TETs but results are limited and almost controversial. Finally, the future of PET/CT and theranostics in TETs is still to be defined but more detailed analysis of metabolic data (such as texture analysis applied on thymic neoplasms), along with promising preclinical and clinical results from new "stromal PET tracers", leave us an increasingly optimistic outlook. CONCLUSIONS: PET plays different roles in the management of thymic epithelial tumours, and its applications may be of help for physicians in different clinical settings.

The Role of PET in Supratentorial and Infratentorial Pediatric Brain Tumors.

OBJECTIVE: This review aims to provide a summary of the clinical indications and limitations of PET imaging with different radiotracers, including 18F-fluorodeoxyglucose (18F-FDG) and other radiopharmaceuticals, in pediatric neuro-oncology, discussing both supratentorial and infratentorial tumors, based on recent literature (from 2010 to present). METHODS: A literature search of the PubMed/MEDLINE database was carried out searching for articles on the use of PET in pediatric brain tumors. The search was updated until December 2020 and limited to original studies published in English after 1 January 2010. RESULTS: 18F-FDG PET continues to be successfully employed in different settings in pediatric neuro-oncology, including diagnosis, grading and delineation of the target for stereotactic biopsy, estimation of prognosis, evaluation of recurrence, treatment planning and assessment of treatment response. Nevertheless, non-18F-FDG tracers, especially amino acid analogues seem to show a better performance in each clinical setting. CONCLUSIONS: PET imaging adds important information in the diagnostic work-up of pediatric brain tumors. International or national multicentric studies are encouraged in order to collect larger amount of data.

Diagnostic Performance of PET Imaging Using Different Radiopharmaceuticals in Prostate Cancer According to Published Meta-Analyses.

A significant number of meta-analyses reporting data on the diagnostic performance of positron emission tomography (PET) in prostate cancer (PCa) is currently available in the literature. In particular, different PET radiopharmaceuticals were used for this purpose. The aim of this review is to summarize information retrieved by published meta-analyses on this topic. The first step included a systematic search of the literature (last search date: June 2020), screening two databases (PubMed/MEDLINE and Cochrane Library). This combination of key words was used: (A) "PET" OR "positron emission tomography" AND (B) "prostate" OR "prostatic" AND (C) meta-analysis. Only meta-analyses on Positron Emission Tomography/Computed Tomography (PET/CT) or Positron Emission Tomography/Magnetic Resonance (PET/MR) in PCa were selected. We have summarized the diagnostic performance of PET imaging in PCa, taking into account 39 meta-analyses published in the literature. Evidence-based data showed the good diagnostic performance of PET/CT with several radiopharmaceuticals, including prostate-specific membrane antigen (PSMA)-targeted agents, radiolabeled choline, fluciclovine, and fluoride in restaging and staging settings. Less evidence-based data were available for PET/MR with different radiotracers. More prospective multicentric studies and cost-effectiveness analyses are warranted.

Prognostic significance of normalized FDG-PET parameters in patients with multiple myeloma undergoing induction chemotherapy and autologous hematopoietic stem cell transplantation: a retrospective single-center evaluation.

PURPOSE: The purpose of this study was to determine retrospectively, through a single-center evaluation, whether FDG PET-CT normalized semi-quantitative parameters may predict response to induction chemotherapy (iChT) and hematopoietic stem cell transplantation (HSCT), as well as disease progression and progression-free survival in multiple myeloma (MM) patients, thus becoming a tool of personalized medicine. METHODS: Patients undergoing iChT and HSCT with baseline and post-treatment FDG PET-CTs from January 2008 to July 2015 were included. The following baseline and post-treatment parameters were obtained: SUVmax, SUVmean, SUVpeak, MTVsum, TLGsum, rPET (lesion SUVmax/liver SUVmax) and qPET (lesion SUVpeak/liver SUVmean). Baseline-to-post-treatment changes (Δ) were also calculated. Metabolic and clinical laboratory progression or response at follow-up were noted; time-to-metabolic-progression (TMP) was defined as the interval from post-treatment scan to eventual progression at follow-up FDG PET-CTs. Possible association between each functional parameter and metabolic/clinical-laboratory progression or response was determined. Kaplan-Meier curves allowed to depict the TMP trend according to FDG PET-CT parameters. RESULTS: Twenty-eight patients were included. Significantly higher ΔrPET and ΔqPET values were observed in ten patients with "metabolic response", with respect to 18 patients having "metabolic progression" (median 0.62 [IQR 0.32 - 1.34] vs median 0.00 [IQR -0.25 - 0.49] for ΔrPET; P = 0.045; median 0.51 [IQR 0.32 - 1.13] vs median 0.00 [IQR -0.31 - 0.67] for ΔqPET; P = 0.035). Neither normalized nor non normalized parameters differed significantly between the 20 patients with "clinical-laboratory response" and the eight patients with "clinical-laboratory progression". ΔrPET value lower than 0.38 and ΔqPET value lower than 0.27 predicted a significantly shorter TMP (P = 0.003 and P = 0.005, respectively). CONCLUSIONS: Normalized semi-quantitative parameters are effective in predicting persistent response to treatment and shorter TMP in patients with MM undergoing iChT and HSCT.

Diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography in gallbladder cancer: A meta-analysis.

AIM: To meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the evaluation of primary tumor in patients with gallbladder cancer (GBCa). METHODS: A comprehensive literature search of studies published through 30(th) June 2014 regarding the role of (18)F-FDG PET and PET/CT in the evaluation of primary gallbladder cancer (GBCa) was performed. All retrieved studies were reviewed. Pooled sensitivity and specificity of (18)F-FDG PET or PET/CT in the evaluation of primary GBCa were calculated. The area under the summary receiving operator characteristics curve (AUC) was calculated to measure the accuracy of these methods. Sub-analyses considering the device used (PET vs PET/CT) were carried out. RESULTS: Twenty-one studies comprising 495 patients who underwent (18)F-FDG PET or PET/CT for suspicious GBCa were selected for the systematic review. The meta-analysis of 13 selected studies provided the following results: sensitivity 87% (95%CI: 82%-92%), specificity 78% (95%CI: 68%-86%). The AUC was 0.88. Improvement of sensitivity and specificity was observed when PET/CT was used. CONCLUSION: (18)F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of primary tumor in GBCa patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. PET/CT seems to have a better diagnostic accuracy than PET alone in this setting.

Evaluation of swallowing function after supracricoid laryngectomy as a primary or salvage procedure.

The primary functional issues following conservative therapy for advanced laryngeal cancer concern swallowing. Here, we evaluated the recovery of swallowing after supracricoid partial laryngectomy (SCL) in patients with primary or recurrent laryngeal cancer. We evaluated the swallowing recovery in 27 SCL patients through oropharyngoesophageal scintigraphy, and we evaluated their quality of life using EORTC questionnaires. Four patients underwent total laryngectomy during follow-up. Patients who retained their larynges were able to feed without nutritional support and without tracheostoma. The only significantly different parameter between the primary and salvage cases was the time elapsed to the removal of nasogastric/PEG tubes, which was longer in salvage cases. SCL has been demonstrated as a valuable option for primary and recurrent laryngeal cancer patients. The present data demonstrate good functional results, particularly in terms of swallowing after previous treatments and in primary settings. The combination of oropharyngoesophageal scintigraphy and questionnaires appears to be an adequate, standardizable approach to assessing swallowing function after SCL.

Diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography in the evaluation of the primary tumor in patients with cholangiocarcinoma: a meta-analysis.

OBJECTIVE: To meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) or PET/computed tomography (PET/CT) for primary tumor evaluation in patients with cholangiocarcinoma (CCa). METHODS: A comprehensive literature search of studies published through December 31, 2013, was performed. Pooled sensitivity and specificity were calculated on a per patient based analysis. Subgroup analyses considering the device used (PET versus PET/CT) and the localization of the primary tumor (intrahepatic cholangiocarcinoma (IH-CCa), extrahepatic cholangiocarcinoma (EH-CCa), and hilar cholangiocarcinoma (H-CCa)) were carried out. RESULTS: Twenty-three studies including 1232 patients were included in the meta-analysis. Pooled sensitivity and specificity of (18)F-FDG-PET or PET/CT were 81% and 82%, respectively. Pooled sensitivity and specificity, respectively, were 80% and 89% for PET, 82% and 75% for PET/CT, 95% and 83% for IH-CCa, 84% and 95% for H-CCa, and 76% and 74% for EH-CCa. CONCLUSIONS: (18)F-FDG-PET and PET/CT were demonstrated to be accurate diagnostic imaging methods for primary tumor evaluation in patients with CCa. These tools have a better diagnostic accuracy in patients with IH-CCa than in patients with EH-CCa. Further studies are needed to evaluate the accuracy of (18)F-FDG-PET or PET/CT in patients with H-CCa.