Diagnostic Performances of PET/CT Using Fibroblast Activation Protein Inhibitors in Patients with Primary and Metastatic Liver Tumors: A Comprehensive Literature Review.

PET/CT using radiolabeled fibroblast activation protein inhibitors (FAPIs) is a promising diagnostic tool in oncology, especially when non-increased and/or physiologically high [18F]FDG uptake (as in liver parenchyma) is observed. We aimed to review the role of PET/CT using radiolabeled FAPIs in primary and/or metastatic liver lesions, and to compare their performances with more "conventional" radiopharmaceuticals. A search algorithm based on the terms "FAPI" AND ("hepatic" OR "liver") was applied, with the last update on 1st January 2024. Out of 177 articles retrieved, 76 studies reporting on the diagnostic application of radiolabeled FAPI PET/CT in at least one patient harboring primary or metastatic liver lesion(s) were fully analyzed. Although there was some heterogeneity in clinical conditions and/or study methodology, PET/CT with radiolabeled FAPIs showed an excellent performance in common primary liver malignancies (hepatocarcinoma, intrahepatic cholangiocarcinoma) and liver metastases (mostly from the gastrointestinal tract and lungs). A higher tumor-to-background ratio for FAPIs than for [18F]FDG was found in primary and metastatic liver lesions, due to lower background activity. Despite limited clinical evidence, radiolabeled FAPIs may be used to assess the suitability and effectiveness of FAPI-derived therapeutic agents such as [177Lu]Lu-FAPI. However, future prospective research on a wider population is needed to confirm the excellent performance.

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.

Is 18F-fluorodeoxyglucose positron emission tomography/computed tomography useful to discriminate metachronous lung cancer from metastasis in patients with oncological history?

BACKGROUND: Solitary pulmonary nodules detected during follow-up in patients with previous cancer history have a high probability of malignancy being either a metachronous lung cancer or a metastasis. This distinction represents a crucial issue in the perspective of "personalized medicine," implying different treatments and prognosis. Aim, to evaluate the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in distinguishing whether solitary pulmonary nodules are metachronous cancers or metastases and the relationship between the nodule's characteristics and their nature. METHODS: From a single-institution database, we retrospectively selected all patients with a previous cancer history who performed 18F-FDG PET/CT to evaluate pulmonary nodules detected during follow-up, ranging from 5 mm to 40 mm, and histologically diagnosed as malignant. RESULTS: Between September 2009 and August 2017, 127 patients (80 males; mean age=70.2±8.5years) with 127 malignant nodules were included: 103/127 (81%) metachronous cancers, 24/127 (19%) metastases. In both groups, PET/CT provided good and equivalent detection rate of malignancy (81% vs. 83%). No differences between metachronous cancers and metastases were found in: patient's age (70.3±8.1 years vs. 69.5±9.7years), gender (males=63.1% vs. 62.5%), interval between previous cancer diagnosis and nodules' detection (median time=4years vs. 4.5years), location (right-lung=55% vs. 54%; upper-lobes=64% vs. 67%; central-site=31% vs. 25%), size (median size=17mm vs. 19.5mm), 18F-FDG standardized uptake value (median SUVmax=5.2 vs. 5.9). CONCLUSIONS: In oncological patients, despite its high detection rate, 18F-FDG PET/CT, as well as any other clinico-anatomical features, cannot distinguish whether a malignant solitary pulmonary nodule is a metachronous lung cancer or a metastasis, supporting the need of histological differential diagnosis.

18F-FDG PET/CT diagnostic performance in solitary and multiple pulmonary nodules detected in patients with previous cancer history: reports of 182 nodules.

PURPOSE: In oncological patients, 18F-FDG PET/CT performance for pulmonary nodules' characterization is not well-established. Thus, the purpose of this study was to evaluate the 18F-FDG PET/CT diagnostic performance in pulmonary nodules detected during follow-up in oncological patients and the relationship between malignancy and nodules' characteristics. METHODS: We retrospectively evaluated 182 pulmonary nodules (121 solitary, 61 multiple; mean size = 16.5 ± 8.1 mm, mean SUVmax = 5.2 ± 5.1) in 148 oncological patients (89 males; mean age = 69.5 ± 8.4 years). Final diagnosis was established by histology or radiological follow-up. Diagnostic performance of 18F-FDG visual analysis (malignancy-criterion: uptake ≥ mediastinal activity), ROC curve analysis for SUVmax and nodules' characteristics were assessed. RESULTS: In 182 nodules, the prevalence of malignancy was 75.8%; PET/CT provided sensitivity = 79%, specificity = 81.8%, accuracy = 79.7%, PPV = 93.1%, NPV = 55.4%; ROC analysis (SUVmax cut-off = 1.7) provided sensitivity = 85.5%, specificity = 72.7%. In 121 solitary nodules, the prevalence of malignancy was 87.6%; PET/CT provided sensitivity = 82.1%, specificity = 73.3%, accuracy = 81%, PPV = 95.6%, NPV = 36.7%; ROC analysis (SUVmax cut-off = 2) provided sensitivity = 84%, specificity = 80%. In 61 multiple nodules, the prevalence of malignancy was 52.5%; PET/CT (nodule and patient-based analysis, respectively) provided sensitivity = 68.7% and 88.9%, specificity = 86.2% and 55.6%, accuracy = 77% and 77.8%, PPV = 84.4% and 80%, NPV = 71.8% and 71.5%; ROC analysis (nodule-based, SUVmax cut-off = 1.8) provided sensitivity = 71.9%, specificity = 82.8%. Malignant nodules were prevalent in males, in solitary pattern and in upper lobes, and had significantly greater size and metabolic activity (SUVmax and TLG) than benign ones, with no differences in interval-time between previous cancer diagnosis and nodule detection, patients' age or other nodules' features (lung side, central/peripheral). When comparing solitary and multiple patterns, malignant nodules had significantly greater size and metabolic activity than benign ones in both groups. CONCLUSIONS: In oncological patients, 18F-FDG PET/CT provides good diagnostic performance for ruling in the malignancy in pulmonary nodules detected during follow-up, even at small size and especially when solitary. In multiple patterns, PET seems useful in the perspective of a personalized management, for identifying the "reference" nodule deserving histological assessment.

Prevalence and malignancy risk of focal colorectal incidental uptake detected by (18)F-FDG-PET or PET/CT: a meta-analysis.

BACKGROUND: The aim of the study was to meta-analyze published data about prevalence and malignancy risk of focal colorectal incidentalomas (FCIs) detected by Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography ((18)F-FDG-PET or PET/CT). METHODS: A comprehensive computer literature search of studies published through July 31(st) 2012 regarding FCIs detected by (18)F-FDG-PET or PET/CT was performed. Pooled prevalence of patients with FCIs and risk of malignant or premalignant FCIs after colonoscopy or histopathology verification were calculated. Furthermore, separate calculations for geographic areas were performed. Finally, average standardized uptake values (SUV) in malignant, premalignant and benign FCIs were reported. RESULTS: Thirty-two studies comprising 89,061 patients evaluated by (18)F-FDG-PET or PET/CT were included. The pooled prevalence of FCIs detected by (18)F-FDG-PET or PET/CT was 3.6% (95% confidence interval [95% CI]: 2.6-4.7%). Overall, 1,044 FCIs detected by (18)F-FDG-PET or PET/CT underwent colonoscopy or histopathology evaluation. Pooled risk of malignant or premalignant lesions was 68% (95% CI: 60-75%). Risk of malignant and premalignant FCIs in Asia-Oceania was lower compared to that of Europe and America. A significant overlap in average SUV was found between malignant, premalignant and benign FCIs. CONCLUSIONS: FCIs are observed in a not negligible number of patients who undergo (18)F-FDG-PET or PET/CT studies with a high risk of malignant or premalignant lesions. SUV is not reliable as a tool to differentiate between malignant, premalignant and benign FCIs. Further investigation is warranted whenever FCIs are detected by (18)F-FDG-PET or PET/CT.

The Role of PET Imaging in Patients with Prion Disease: A Literature Review.

Prion diseases are rare, rapidly progressive, and fatal incurable degenerative brain disorders caused by the misfolding of a normal protein called PrPC into an abnormal protein called PrPSc. Their highly variable clinical presentation mimics various degenerative and non-degenerative brain disorders, making diagnosis a significant challenge for neurologists. Currently, definitive diagnosis relies on post-mortem examination of nervous tissue to detect the pathogenic prion protein. The current diagnostic criteria are limited. While structural magnetic resonance imaging (MRI) remains the gold standard imaging modality for Creutzfeldt-Jakob disease (CJD) diagnosis, positron emission tomography (PET) using 18fluorine-fluorodeoxyglucose (18F-FDG) and other radiotracers have demonstrated promising potential in the diagnostic assessment of prion disease. In this context, a comprehensive and updated review exclusively focused on PET imaging in prion diseases is still lacking. We review the current value of PET imaging with 18F-FDG and non-FDG tracers in the diagnostic management of prion diseases. From the collected data, 18F-FDG PET mainly reveals cortical and subcortical hypometabolic areas in prion disease, although fails to identify typical pattern or laterality abnormalities to differentiate between genetic and sporadic prion diseases. Although the rarity of prion diseases limits the establishment of a definitive hypometabolism pattern, this review reveals some more prevalent 18F-FDG patterns associated with each disease subtype. Interestingly, in both sporadic and genetic prion diseases, the hippocampus does not show significant glucose metabolism alterations, appearing as a useful sign in the differential diagnosis with other neurodegenerative disease. In genetic prion disease forms, PET abnormality precedes clinical manifestation. Discordant diagnostic value for amyloid tracers among different prion disease subtypes was observed, needing further investigation. PET has emerged as a potential valuable tool in the diagnostic armamentarium for CJD. Its ability to visualize functional and metabolic brain changes provides complementary information to structural MRI, aiding in the early detection and confirmation of CJD.

Breast Relapse of Pediatric B-Cell Acute Lymphoblastic Leukemia After CAR-T Therapy Detected by 18F-FDG PET/CT.

BACKGROUND: B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy. Medullary and extramedullary disease relapse is a well-known occurrence in B-ALL pediatric patients treated with standard chemo-immunotherapy and, more recently, with chimeric antigen receptor (CAR)-T cell therapy. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) emerges as a sensitive imaging tool for detecting disease relapse at extra-medullary sites, with only limited literature evidence in the CAR-T therapy setting. CASE REPORT: In a 12-year-old female treated with CAR-T therapy for B-ALL relapse, 18F-FDG PET/CT scan performed for surveillance, after disease remission, detected a solitary and clinically occult relapse in the breast parenchyma that was histologically confirmed. CONCLUSION: At our knowledge, this is the first report about a pediatric B-ALL patient with a solitary and occult breast relapse after CAR-T therapy, early discovered by 18F-FDG PET/CT during disease monitoring.

PET/CT with Fibroblast Activation Protein Inhibitors in Breast Cancer: Diagnostic and Theranostic Application-A Literature Review.

Growing studies have recently reported on the promising application of radiolabeled-fibroblast activation protein inhibitors (FAPIs) as diagnostic and therapeutic agents in various oncological populations. To exclusively evaluate the current evidence on the diagnostic and therapeutic role of FAPI radiotracers in patients with breast cancer (BC), a narrative review of the available literature was performed. A search algorithm from PubMed/MEDLINE, based on the combination of "PET" OR "positron emission tomography" and "FAPI" and "cancer", with a last update in February 2022, was applied. From 233 identified articles, 33 studies conducted in BC patients and with available data on PET imaging or radiolabeled-FAPI therapy were finally considered, for a total of 191 patients. Despite some clinical and methodological heterogeneity among the reviewed articles, 68Ga-FAPI PET/CT emerges as a valuable diagnostic tool in BC patients both at staging and restaging, also demonstrating several technical advantages and an overall better performance than 18F-FDG, especially in histotypes with well-known low 18F-FDG avidity. Moreover, although with still limited clinical evidence in BC, radiolabeled FAPIs emerge as promising therapeutic agents in a theranostic perspective, increasing the possibility of more personalized treatments. From these results, future research directions on FAPI radiotracers application in BC patients are suggested.

The impact of intensified staging and combined therapies in locally advanced pancreatic cancer: a secondary analysis of prospective studies.

AIM: To investigate the use of comprehensive pre-treatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18FFDG-PET/CT scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies. MATERIALS AND METHODS: This study was a secondary analysis of three prospective studies of chemoradiotherapy (CRT) with or without induction chemotherapy (IC). The inclusion period was from December 2009 until February 2023. An intensified pretreatment staging was conducted for all LAPC patients. Patients without distant disease at initial staging, with borderline resectable or unresectable LAPC, were enrolled in chemoradiotherapy combination protocols (CRT with or without IC). IC regimens included GemOx or FOLFIRINOX for four cycles, followed by concurrent CRT with gemcitabine. The primary endpoint was the detection of occult metastatic disease, and secondary objectives included resection rate, treatment toxicity, overall survival (OS), progression-free survival (PFS), local control (LC), and metastasis-free survival (MFS). RESULTS: Out of the 134 LAPC patients, 33.5% were identified with metastatic disease. Of these, 23.1% had a positive exploratory laparoscopy. Additionally, 13.4% were identified as having distant metastases by 18-FDG PET/CT. The median PFS for all patients who completed CRT was 14.3 months, and the median OS was 17.2 months. Resected patients after the combined therapies demonstrated significantly improved outcomes compared to non-resected patients (median PFS, 22.5 mo vs. 9.5 mo, P<0.001; median OS, 38.2 mo vs. 13 mo, P<0.001). Moreover, patients treated with IC followed by CRT showed significantly better outcomes compared to upfront CRT group (median PFS, 19 mo vs. 9.9 mo, P<0.001; median OS, 19.3 mo vs. 14.6 mo, P<0.001). At univariate logistic regression analysis, the adding of IC was the only predictor for resection rate (95% CI 0.12-1.02, P=0.05), and this data was confirmed at multivariate analysis (95% CI 0.09-0.98, P=0.04). Haematological and gastrointestinal toxicities were observed during treatment, with manageable adverse events. CONCLUSIONS: The use of comprehensive pre-treatment staging, including laparoscopy and 18F-FDG-PET/CT scan, is an effective approach in identifying occult metastatic disease in LAPC patients. Our findings offer valuable insights into accurate staging and treatment efficacy, providing evidence-based support for optimal management strategies in LAPC patients.

¹8F-fluoro-deoxy-glucose focal uptake in very small pulmonary nodules: fact or artifact? Case reports.

BACKGROUND: 18F-fluoro-deoxy-glucose (18 F-FDG) positron emission tomography integrated/combined with computed tomography (PET-CT) provides the best diagnostic results in the metabolic characterization of undetermined solid pulmonary nodules. The diagnostic performance of 18 F-FDG is similar for nodules measuring at least 1 cm and for larger masses, but few data exist for nodules smaller than 1 cm. CASE PRESENTATION: We report five cases of oncologic patients showing focal lung 18 F-FDG uptake on PET-CT in nodules smaller than 1 cm. We also discuss the most common causes of 18 F-FDG false-positive and false-negative results in the pulmonary parenchyma.In patient 1, contrast-enhanced CT performed 10 days before PET-CT did not show any abnormality in the site of uptake; in patient 2, high-resolution CT performed 1 month after PET showed a bronchiole filled with dense material interpreted as a mucoid impaction; in patient 3, contrast-enhanced CT performed 15 days before PET-CT did not identify any nodules; in patients 4 and 5, contrast-enhanced CT revealed a nodule smaller than 1 cm which could not be characterized. The 18 F-FDG uptake at follow-up confirmed the malignant nature of pulmonary nodules smaller than 1 cm which were undetectable, misinterpreted, not recognized or undetermined at contrast-enhanced CT. CONCLUSION: In all five oncologic patients, 18 F-FDG was able to metabolically characterize as malignant those nodules smaller than 1 cm, underlining that: 18 F-FDG uptake is not only a function of tumor size but it is strongly related to the tumor biology; functional alterations may precede morphologic abnormalities. In the oncologic population, especially in higher-risk patients, PET can be performed even when the nodules are smaller than 1 cm, because it might give an earlier characterization and, sometimes, could guide in the identification of alterations missed on CT.

Is there a role for fluorine 18 fluorodeoxyglucose-positron emission tomography and positron emission tomography/computed tomography in evaluating patients with mycobacteriosis? A systematic review.

OBJECTIVE: This study was designed to review the emerging role of fluorine 18 fluorodeoxyglucose (¹8F-FDG)-positron emission tomography (PET) CT/computed tomography (PET/CT) in patients with mycobacteriosis. METHODS: A comprehensive literature search of published studies through October 2010 in PubMed/MEDLINE database regarding ¹8F-FDG-PET and PET/CT in patients with mycobacteriosis was performed. RESULTS: Ultimately, we identified 16 studies comprising a total of 220 patients with mycobacteriosis. Main findings of the included studies are presented. CONCLUSIONS: (1) Mycobacteriosis commonly causes increased ¹8F-FDG uptake; therefore, positive ¹8F-FDG-PET results should be interpreted with caution in differentiating benign from malignant abnormalities. (2) ¹8F-FDG-PET and PET/CT are potentially useful in detecting sites of Mycobacterium infection. (3) Dual-phase ¹8F-FDG-PET is not useful for the differential diagnosis between malignant lesions and sites of Mycobacterium infection. (4) ¹8F-FDG-PET and PET/CT are useful for the evaluation of disease activity and in monitoring response to therapy in patients with mycobacteriosis. (5) Dual-tracer PET and PET/CT are potentially useful for presumptive diagnosis of solitary pulmonary nodules.

Bone Marrow Activation After Chemotherapy Presenting as Diffuse Skeletal Uptake on 18F-Fluorocholine PET/CT.

ABSTRACT: Diffuse 18F-FDG skeletal uptake due to chemotherapy-induced bone marrow activation is well documented, whereas it has never been reported with 18F-fluorocholine. We described a patient with pelvic recurrence of prostate cancer at 18F-fluorocholine PET/CT. A second PET/CT after docetaxel showed minimal residual activity in pelvis, but it revealed diffuse, intense 18F-fluorocholine skeletal uptake. Considering biochemical and metabolic response and absence of morphologically suspected bone lesions, skeletal hyperactivity was interpreted as chemotherapy-related bone marrow rebound rather than diffuse metastatic involvement, as confirmed by its resolution after treatment ended. The occurrence of such 18F-fluorocholine pattern should be considered to avoid imaging misinterpretation.

The Prognostic Value of 18F-FDG PET Imaging at Staging in Patients with Malignant Pleural Mesothelioma: A Literature Review.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy, frequently diagnosed at locally-advanced/metastatic stages. Due to a very poor prognosis and limited treatment options, the need to identify new prognostic markers represents a great clinical challenge. The prognostic role of metabolic information derived from Positron Emission Tomography (PET) with 18F-Fluoro-deoxy-glucose (18F-FDG) has been investigated in different MPM settings, however with no definitive consensus. In this comprehensive review, the prognostic value of FDG-PET imaging exclusively performed at staging in MPM patients was evaluated, conducting a literature search on PubMed/MEDLINE from 2010 to 2020. From the 19 selected studies, despite heterogeneity in several aspects, staging FDG-PET imaging emerges as a valuable prognostic biomarker, with higher tumor uptake predictive of worse prognosis, and with volumetric metabolic parameters like Metabolic Tumor Volume, (MTV) and Total Lesion Glycolisis (TLG) performing better than SUVmax. However, PET uptake parameters were not always confirmed as independent prognostic factors, especially in patients previously treated with pleurodesis and with a non-epithelioid histotype. Future prospective studies in larger and clinically homogeneous populations, and using more standardized methods of PET images analysis, are needed to further validate the value of staging FDG-PET in the prognostic MPM stratification, with a potential impact on better patient-tailored treatment planning, in the perspective of personalized medicine.

Short 2-[18F]Fluoro-2-Deoxy-D-Glucose PET Dynamic Acquisition Protocol to Evaluate the Influx Rate Constant by Regional Patlak Graphical Analysis in Patients With Non-Small-Cell Lung Cancer.

Purpose: To test a short 2-[18F]Fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET dynamic acquisition protocol to calculate Ki using regional Patlak graphical analysis in patients with non-small-cell lung cancer (NSCLC). Methods: 24 patients with NSCLC who underwent standard dynamic 2-[18F]FDG acquisitions (60 min) were randomly divided into two groups. In group 1 (n = 10), a population-based image-derived input function (pIDIF) was built using a monoexponential trend (10-60 min), and a leave-one-out cross-validation (LOOCV) method was performed to validate the pIDIF model. In group 2 (n = 14), Ki was obtained by standard regional Patlak plot analysis using IDIF (0-60 min) and tissue response (10-60 min) curves from the volume of interests (VOIs) placed on descending thoracic aorta and tumor tissue, respectively. Moreover, with our method, the Patlak analysis was performed to obtain Ki,s using IDIFFitted curve obtained from PET counts (0-10 min) followed by monoexponential coefficients of pIDIF (10-60 min) and tissue response curve obtained from PET counts at 10 min and between 40 and 60 min, simulating two short dynamic acquisitions. Both IDIF and IDIFFitted curves were modeled to assume the value of 2-[18F]FDG plasma activity measured in the venous blood sampling performed at 45 min in each patient. Spearman's rank correlation, coefficient of determination, and Passing-Bablok regression were used for the comparison between Ki and Ki,s. Finally, Ki,s was obtained with our method in a separate group of patients (group 3, n = 8) that perform two short dynamic acquisitions. Results: Population-based image-derived input function (10-60 min) was modeled with a monoexponential curve with the following fitted parameters obtained in group 1: a = 9.684, b = 16.410, and c = 0.068 min-1. The LOOCV error was 0.4%. In patients of group 2, the mean values of Ki and Ki,s were 0.0442 ± 0.0302 and 0.33 ± 0.0298, respectively (R 2 = 0.9970). The Passing-Bablok regression for comparison between Ki and Ki,s showed a slope of 0.992 (95% CI: 0.94-1.06) and intercept value of -0.0003 (95% CI: -0.0033-0.0011). Conclusions: Despite several practical limitations, like the need to position the patient twice and to perform two CT scans, our method contemplates two short 2-[18F]FDG dynamic acquisitions, a population-based input function model, and a late venous blood sample to obtain robust and personalized input function and tissue response curves and to provide reliable regional Ki estimation.

Application of Artificial Neural Network to Preoperative 18F-FDG PET/CT for Predicting Pathological Nodal Involvement in Non-small-cell Lung Cancer Patients.

Purpose: To evaluate the performance of artificial neural networks (aNN) applied to preoperative 18F-FDG PET/CT for predicting nodal involvement in non-small-cell lung cancer (NSCLC) patients. Methods: We retrospectively analyzed data from 540 clinically resectable NSCLC patients (333 M; 67.4 ± 9 years) undergone preoperative 18F-FDG PET/CT and pulmonary resection with hilo-mediastinal lymphadenectomy. A 3-layers NN model was applied (dataset randomly splitted into 2/3 training and 1/3 testing). Using histopathological reference standard, NN performance for nodal involvement (N0/N+ patient) was calculated by ROC analysis in terms of: area under the curve (AUC), accuracy (ACC), sensitivity (SE), specificity (SP), positive and negative predictive values (PPV, NPV). Diagnostic performance of PET visual analysis (N+ patient: at least one node with uptake ≥ mediastinal blood-pool) and of logistic regression (LR) was evaluated. Results: Histology proved 108/540 (20%) nodal-metastatic patients. Among all collected data, relevant features selected as input parameters were: patients' age, tumor parameters (size, PET visual and semiquantitative features, histotype, grading), PET visual nodal result (patient-based, as N0/N+ and N0/N1/N2). Training and testing NN performance (AUC = 0.849, 0.769): ACC = 80 and 77%; SE = 72 and 58%; SP = 81 and 81%; PPV = 50 and 44%; NPV = 92 and 89%, respectively. Visual PET performance: ACC = 82%, SE = 32%, SP = 94%; PPV = 57%, NPV = 85%. Training and testing LR performance (AUC = 0.795, 0.763): ACC = 75 and 77%; SE = 68 and 55%; SP = 77 and 82%; PPV = 43 and 43%; NPV = 90 and 88%, respectively. Conclusions: aNN application to preoperative 18F-FDG PET/CT provides overall good performance for predicting nodal involvement in NSCLC patients candidate to surgery, especially for ruling out nodal metastases, being NPV the best diagnostic result; a high NPV was also reached by PET qualitative assessment. Moreover, in such population with low a priori nodal involvement probability, aNN better identify the relatively few and unexpected nodal-metastatic patients than PET analysis, so supporting the additional aNN use in case of PET-negative images.

Dynamic 11C-Methionine PET-CT: Prognostic Factors for Disease Progression and Survival in Patients with Suspected Glioma Recurrence.

PURPOSE: The prognostic evaluation of glioma recurrence patients is important in the therapeutic management. We investigated the prognostic value of 11C-methionine PET-CT (MET-PET) dynamic and semiquantitative parameters in patients with suspected glioma recurrence. METHODS: Sixty-seven consecutive patients who underwent MET-PET for suspected glioma recurrence at MR were retrospectively included. Twenty-one patients underwent static MET-PET; 46/67 underwent dynamic MET-PET. In all patients, SUVmax, SUVmean and tumour-to-background ratio (T/B) were calculated. From dynamic acquisition, the shape and slope of time-activity curves, time-to-peak and its SUVmax (SUVmaxTTP) were extrapolated. The prognostic value of PET parameters on progression-free (PFS) and overall survival (OS) was evaluated using Kaplan-Meier survival estimates and Cox regression. RESULTS: The overall median follow-up was 19 months from MET-PET. Recurrence patients (38/67) had higher SUVmax (p = 0.001), SUVmean (p = 0.002) and T/B (p < 0.001); deceased patients (16/67) showed higher SUVmax (p = 0.03), SUVmean (p = 0.03) and T/B (p = 0.006). All static parameters were associated with PFS (all p < 0.001); T/B was associated with OS (p = 0.031). Regarding kinetic analyses, recurrence (27/46) and deceased (14/46) patients had higher SUVmaxTTP (p = 0.02, p = 0.01, respectively). SUVmaxTTP was the only dynamic parameter associated with PFS (p = 0.02) and OS (p = 0.006). At univariate analysis, SUVmax, SUVmean, T/B and SUVmaxTTP were predictive for PFS (all p < 0.05); SUVmaxTTP was predictive for OS (p = 0.02). At multivariate analysis, SUVmaxTTP remained significant for PFS (p = 0.03). CONCLUSION: Semiquantitative parameters and SUVmaxTTP were associated with clinical outcomes in patients with suspected glioma recurrence. Dynamic PET-CT acquisition, with static and kinetic parameters, can be a valuable non-invasive prognostic marker, identifying patients with worse prognosis who require personalised therapy.

Atypical Presentation of COVID-19 Incidentally Detected at 18F-FDG PET/CT in an Asymptomatic Oncological Patient.

The incidence of COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, is rapidly growing worldwide. In this pandemic period, the chance of incidental pulmonary findings suggestive of COVID-19 at F-FDG PET/CT in asymptomatic oncological patients is not negligible. To suspect COVID-19 is more demanding whether its presentation is atypical. We describe the incidental PET/CT detection of an F-FDG-avid isolated centrilobular pulmonary consolidation in an asymptomatic lymphoma patient, which later resulted in an unexpected and atypical COVID-19 presentation. The nuclear medicine physicians should be prepared to suspect COVID-19 even in asymptomatic patients presenting with a "far-from-COVID-19" finding at PET/CT.

Which Is the Optimal Scan Time of 18F-DOPA PET/CT in Patients With Recurrent Medullary Thyroid Carcinoma?: Results From a Dynamic Acquisition Study.

PURPOSE: The aim of this retrospective study was to determine, by dynamic acquisition, the optimal scan time of F-DOPA PET/CT in patients with recurrent medullary thyroid carcinoma (MTC). METHODS: Twenty-one patients with suspected recurrent MTC underwent dynamic F-DOPA PET/CT (lasting 45 minutes) followed by whole-body scan. Three different time intervals of dynamic acquisition were evaluated: ultra-early phase (2-5 minutes), early phase (5-10 minutes), and late phase (40-45 minutes). The number and SUVmax of all detected lesions among the 3 dynamic acquisition phases were compared on qualitative and semiquantitative analyses. Time-activity curves, SUVmax washout rate between ultra-early or early phase and late phase, and signal-to-noise ratio (SNR) between lesion and background activity were also calculated. RESULTS: At dynamic acquisition, 15 of 21 patients were classified as PET-positive and 6 of 21 as PET-negative, with overall 21 detected lesions. Ultra-early and early imaging provided a better lesion visualization than late phase in more than 70% of cases, as also reflected by SNR (mean SNR reduction between 2 and 45 minutes, -45% ± 19%). Time-activity curves showed a rapid tracer accumulation in MTC lesions, with an average maximum uptake at 2 minutes after injection. Mean lesion SUVmax was 2-fold higher in ultra-early frames compared with last frames (mean washout rate, -44% ± 33%). Finally, compared with whole-body imaging in the same field of view, dynamic acquisition identified 1 additional positive patient and 3 additional lesions in 2 patients. CONCLUSIONS: Our study, showing a very fast F-DOPA uptake in MTC lesions, suggests the utility to obtain early PET/CT images, already at 2 to 5 minutes after tracer injection, when maximum lesion tracer uptake is reached.

A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer.

Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level > 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66-19.47; p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64-57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9-10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (>90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients.