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Opinion statementNeuroendocrine neoplasms (NEN) are a heterogeneous group of tumours derived from cells of neuroendocrine origin and can potentially arise everywhere in the human body. The diagnostic assessment of NEN can be performed using a variety of PET radiopharmaceuticals. Well-differentiated NEN (NET) present a high expression of SSTR (somatostatin receptors) and can therefore be studied with 68Ga-DOTA-peptides ([68Ga]Ga-DOTANOC, [68Ga]Ga-DOTATOC, [68Ga]Ga-DOTATATE). Current guidelines recommend the use of SSTR imaging to assess disease extension at staging/restaging, follow-up, assessment of response to therapy and selection of patients who may benefit from radionuclide therapy (PRRT). [18F]F-FDG is used for the assessment of high-grade tumours (high-grade G2, G3 and NEC) and in every case, there is one or more mismatched lesions between diagnostic CT (positive) and SSTR-PET/CT (negative). [18F]F-DOPA is currently used for the assessment of medullary thyroid carcinoma, neuroblastoma, primary pheochromocytoma and abdominal paraganglioma. In recent years, however, several new tracers were designed exploiting the many potential targets of the neuroendocrine cell and were employed in clinical trials for both imaging and therapy. Currently, the real-life clinical impact of these tracers is still mostly not known; however, the favourable biodistribution (e.g. [68Ga]Ga-FAPI, SSTR antagonists) and the possibility to use new theranostic pairs may provide novel diagnostic as well as therapeutic options (e.g. [68Ga]Ga-PSMA, [64Cu]Cu-SARTATE, [68Ga]Ga-CXCR4) for NEN patients.

Non-Hodgkin lymphomas represents a heterogeneous group of lymphoproliferative disorders characterized by different clinical courses, varying from indolent to highly aggressive.

This atlas is intended to enable nuclear medicine practitioners who routinely read PET/CT scans to recognize the most common CT abnormalities. Reading PET/CT scans can sometimes be challenging. It is not infrequent, in fact, to encounter abnormal findings in CT images (not related to the neoplastic disease under evaluation) that are functionally silent and therefore difficult to interpret for nuclear medicine practitioners. Frequently, these findings are clinically relevant and should be reported, interpreted and compared to previous scans. This may also have an impact on patient management, since expensive tests like PET/CT are expected to provide the highest level of diagnostic information. Generally, CT images associated with a PET scan are acquired in a low-dose modality, and therefore prove to be sub-optimal for CT image interpretation. Sometimes a comparison with a full-resolution and contrast-enhanced CT atlas may be difficult. Low-dose CT slices are thicker than diagnostic CT and offer less anatomical detail, which can affect accuracy in terms of recognizing both anatomical structures and pathological findings.

Simple Summary The purpose of the present study is to describe the frequency of non-malignant [68Ga]Ga-DOTANOC uncinate process (UP) uptake and to evaluate its variations over time. Among the first 6 months of enrolment of a monocentric prospective observational electronic archive, analyses of a large number of PET/CT scans (n = 268) of NEN pts (n = 172) demonstrated that: UP uptake is a frequent finding (observed in almost half of the cases, slightly higher than previously reported), mostly presenting with a diffuse pattern and, interestingly, characterized by variations over time in almost one third of the cases. The consciousness of this diagnostic pitfall is of utmost importance for accurate [68Ga]Ga-DOTANOC PET/CT reporting, since the pancreas represents one of the most frequent sites of NEN. Purpose: [68Ga]Ga-DOTA-peptide uptake in the pancreatic head/uncinate process (UP) is a frequent PET/CT finding. Although mostly physiologic, it can represent a pitfall in PET/CT reading, especially when focal. An increased frequency of UP uptake has been reported in patients (pts) affected by diabetes mellitus (DM). The aim of the study is to describe the frequency of [68Ga]Ga-DOTANOC UP uptake to evaluate its variations over time and its possible correlation with DM. Methods: In September 2017, a monocentric prospective observational electronic archive was initiated at our center to collect clinical and imaging data of pts undergoing [68Ga]Ga-DOTANOC PET/CT. Among the pts enrolled in the first 6 months (Sept 2017 to Feb 2018), those presenting [68Ga]Ga-DOTANOC PET/CT uptake at UP level were included. Pts with UP lesions already documented on CT/MRI or those that underwent surgical excision of UP before PET/CT were excluded from the analysis. [68Ga]Ga-DOTANOC UP uptake was classified as diffuse or focal and compared with the pattern observed in previous PET/CT scans performed at our center. An increased frequency of UP uptake was also correlated with the presence of DM. Results: In the first 6 months, 253 pts were enrolled in the archive and 172 out of them were included in the analysis. UP increased uptake was frequently observed (77/172, 44.8%) and was mostly diffuse (62/77). In 75/172 pts (43.6%), previous [68Ga]Ga-DOTANOC PET/CT scans were available (overall 268 scans; number of previous PET per pt range: 1-20) and were retrospectively reviewed. Despite the fact that, in most pts, the uptake pattern was stable over time (54/75 pts, 72%), it changed in approximately one third of cases (21/75, 28%). Among DM pts (29/172), only 10/29 (34.4%) presented increased UP uptake. Conclusions: UP [68Ga]Ga-DOTANOC uptake is a frequent non-malignant finding (slightly higher than previously reported), mostly presenting with a diffuse pattern. However, contrary to previous reports, our data show that the pattern of uptake may vary over time in approximately one third of the cases and it is not more frequently observed in pts with DM.

Objectives: To assess how patients’ dependent parameters may affect [68Ga]Ga-DOTANOC image quality and to propose a theoretical body mass index (BMI)-adjusted injected activity (IA) scheme, to improve imaging of high weight patients. Methods: Among patients prospectively enrolled (June-2019 and May-2020) in an Institutional Ethical Committee-approved electronic archive, we included those affected by primary gastro-entero-pancreatic (GEP) or lung neuroendocrine tumour and referred by our Institutional clinicians (excluding even minimal radiopharmaceutical extravasation, movement artefacts, renal insufficiency). All PET/CT images were acquired following EANM guidelines and rated for visual quality (1 = non-diagnostic, 2 = poor, 3 = moderate, 4 = good). Collected data included patient’s body mass, height, BMI, age, IA (injected activity), IA/Kg (IAkg), IA/BMI (IABMI), liver SUVmean, liver SUVmax standard deviation, liver-signal-to-noise (LSNR), normalised_LSNR (LSNR_norm) and contrast-to-noise ratio (CNR) for positive scans and were compared to image rating (poor vs moderate/good). Results: Overall, 77 patients were included. Rating concordance was high (agreement = 81.8%, Fleiss k score = 0.806). All patients’ dependent parameters resulted significantly different between poor-rated and moderate/good-rated scans (IA: p = 0.006, IAkg: p =< 0.001, body weight: p =< 0.001, BMI: p =< 0.001, IABMI: p =< 0.001). Factors significantly associated with moderate/good rating were BMI (p =< 0.001), body weight (p =< 0.001), IABMI (p =< 0.001), IAkg (p = 0.001), IA (p = 0.003), LSNR_norm (p = 0.01). The BMI-based model presented the best predictive efficiency (81.82%). IABMI performance to differentiate moderate/good from poor rating resulted statistically significant (IA-AUC = 0.78; 95% CI: 0.68–0.89; cut-off value of 4.17 MBq*m2/kg, sensitivity = 81.1%, specificity = 66.7%). If BMI-adjusted IA (=4.17*BMI) would have been applied in this population, the median IA would have slightly inferior (−4.8%), despite a different IA in each patient. Advances in knowledge: BMI resulted the best predictor of image quality. The proposed theoretical BMI-adjusted IA scheme (4.17*BMI) should yield images of better quality (especially in high-BMI patients) maintaining practical scanning times (3 min/bed).

Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with 68Ga for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [68Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [18F]FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 > 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18F (to overcome the limits imposed by 68Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs.

Aim/Introduction: Digital PET/CT allows Q.Clear image reconstruction with different Beta (β) levels. However, no definitive standard β level for [68Ga]Ga-DOTANOC PET/CT has been established yet. As patient’s body mass index (BMI) can affect image quality, the aim of the study was to visually and semi-quantitatively assess different β levels compared to standard OSEM in overweight patients. Materials and methods: Inclusion criteria: (1) patients with NEN included in a prospective CE-approved electronic archive; (2) [68Ga]Ga-DOTANOC PET/CT performed on a digital tomograph between September2019/March2021; (3) BMI ≥ 25. Images were acquired following EANM guidelines and reconstructed with OSEM and Q.Clear with three β levels (800, 1000, 1600). Scans were independently reviewed by three expert readers, unaware of clinical data, who independently chose the preferred β level reconstruction for visual overall image quality. Semi-quantitative analysis was performed on each scan: SUVmax of the highest uptake lesion (SUVmax-T), liver background SUVmean (SUVmean-L), SUVmax-T/SUVmean-L, Signal-to-noise ratio for both liver (LSNR) and the highest uptake lesion (SNR-T), Contrast-to-noise ratio (CNR). Results: Overall, 75 patients (median age: 63years old [23–87]) were included: pre-obesity sub-group (25 ≤ BMI < 30, n = 50) and obesity sub-group (BMI ≥ 30, n = 25). PET/CT was positive for disease in 45/75 (60.0%) cases (14 obese and 31 pre-obese patients). Agreement among readers’ visual rating was high (Fleiss κ = 0.88) and the β1600 was preferred in most cases (in 96% of obese patients and in 53.3% of pre-obese cases). OSEM was considered visually equal to β1600 in 44.7% of pre-obese cases and in 4% of obese patients. In a minority of pre-obese cases, OSEM was preferred (2%). In the whole population, CNR, SNR-T and LSNR were significantly different (p < 0.001) between OSEM and β1600, conversely to SUVmean-L (not significant). These results were also confirmed when calculated separately for the pre-obesity and obesity sub-groups β800 and β1000 were always rated inferior. Conclusions: Q.Clear is a new technology for PET/CT image reconstruction that can be used to increase CNR and SNR-T, to subsequently optimise overall image quality as compared to standard OSEM. Our preliminary data on [68Ga]Ga-DOTANOC PET/CT demonstrate that in overweight NEN patients, β1600 is preferable over β800 and β1000. Further studies are warranted to validate these results in lesions of different anatomical region and size; moreover, currently employed interpretative PET positivity criteria should be adjusted to the new reconstruction method.

The aim of this guideline is to provide standards for the recommendation, performance, interpretation, and reporting of [18F]Fluciclovine PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of [18F]Fluciclovine PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.

Purpose: To evaluate the role of F-18-Fluorothymidine (FLT) PET/CT in lymphoma patients with suspected recurrent or residual disease. Methods: Adult lymphoma patients presenting with positive or equivocal F-18-FDG PET/CT at end-treatment or follow-up were prospectively addressed to an additional F-18-FLT-PET/CT. SUV max and tumour-to-background ratios (TBRs) were recorded for the most avid lesion. Biopsy or, when not available, clinical or imaging assessment were employed as standard of reference. Results: Overall 52 patients were recruited. Histology was available in 20/52 patients (38%), proliferation-index (Ki-67) in 14/20. Disease was excluded in 13/52 patients (25%) (one reactive follicular hyperplasia, five reactive-inflammatory tissues, four reactive nodes, two nodal sarcoid-like and one non-specific peri-caecal finding). FDG and FLT scans were concordant in disease restaging in 34/52 patients (65%), whereas in 18/52 cases (35%) relevant discrepancies were recorded. SUV max and TBR were significantly higher in the disease versus the disease-free group, with both tracers (p = 0.0231 and 0.0219 for FDG; p = 0.0008 and 0.0016 for FLT). FLT-SUVmax demonstrated slightly better performance in discriminating benign from malignant lesions (ROC-AUC: 0.8116 and 0.7949 for FLT-SUV max and TBR; 0.7120 and 0.7140 for FDG). Optimal FLT-SUV max cut-offs were searched: three would lead to 95% sensitivity, 81% accuracy, and 39% specificity, whereas seven led to 100%, 41%, and 56% respectively. No statistically significant correlation was observed between the two FLT indices and Ki-67. Conclusions: According to our results in a clinical setting of recurrent or residual lymphoma, FLT is not significantly superior to FDG and it is unlikely that it will be employed independently. FLT may be restricted to a few specific cases, as complementary to standard FDG imaging, to confirm a diagnosis or to define a better target to biopsy. However, due to FLT suboptimal performance, many findings would remain inconclusive, requiring further diagnostic procedures and reducing the effectiveness of performing an additional FLT scan.

The primary aim of the study was to evaluate the role of [18F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [11C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax, target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology, subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected (n = 95). For both tracers, the location of the “blinded” prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [18F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [18F]Fluciclovine or [11C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [18F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively, whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.

Hepatobiliary scintigraphy (HBS) has been demonstrated to predict post-hepatectomy liver failure (PHLF). However, existing cutoff values for future liver remnant function (FLR-F) were previously set according to the “50–50 criteria” PHLF definition. Methods of calculation and fields of application in liver surgery have changed in the meantime. The aim of this study was to demonstrate the role of HBS combined with single photon emission computed tomography (SPECT/CT) in predicting severity of PHLF, according to the International Study Group of Liver Surgery (ISGLS). All patients submitted to major hepatectomy with preoperative HBS-SPECT/CT between November 2016 and December 2019, were analyzed. Patients were resected according to hepatic volumetry. Receiver operating characteristic (ROC) curve analysis was performed to identify cutoffs of FLR function for predicting PHLF according to ISGLS definition and grading. Of the 38 patients enrolled, 26 were submitted to one-stage hepatectomy (living liver donors = 4) and 12 to two-stage procedures (portal vein embolization = 4, ALPPS = 8). Overall, 18 patients developed PHLF according to ISGLS criteria: 12 of grade A (no change in the patient’s clinical management) and 6 of grade B (change in clinical management). ROC analysis established increasingly higher cutoffs of FLR-F for predicting PHLF according to the “50–50 criteria”, ISGLS grade B and ISGLS grade A/B, respectively. HBS with SPECT/CT may help to assess severity of PHLF following major hepatectomy. Prospective multicenter trials are needed to confirm the effective role of HBS-SPECT/CT in liver surgery. Electronic supplementary material The online version of this article (10.1007/s13304-020-00907-2) contains supplementary material, which is available to authorized users.

Incidental finding of [68Ga]Ga-PSMA-avid intraductal papillary mucinous neoplasm

Imaging in hematological diseases has evolved extensively over the past several decades. Positron emission tomography/computed tomography (PET/CT) with of 2-[18 F]-fluoro-2-deoxy-d-glucose ([18 F] FDG) is currently essential for accurate staging and for early and late therapy response assessment for all FDG-avid lymphoproliferative histologies. The widely adopted visual Deauville 5-point scale and Lugano Classification recommendations have recently standardized PET scans interpretation and improved lymphoma patient management. In addition [18 F] FDG-PET is routinely recommended for initial evaluation and treatment response assessment of Multiple Myeloma (MM) with significant contribution in risk-stratification and prognostication, although magnetic resonance imaging remains the Gold Standard for the assessment of bone marrow involvement. In this review, an overview of the role of [18 F] FDG-PET, in hematological malignancies is provided, particularly focusing on Hodgkin lymphoma (HL) and Diffuse Large B Cell Lymphoma (DLBCL), both in adult and pediatric populations, and MM, at each point of patient management. Potential alternative molecular imaging applications in this field, such as non-[18 F] FDG-tracers, whole body magnetic resonance imaging (WB-MRI), hybrid PET/MRI and emerging radiomics research are briefly presented.

Background Graft selection strategy in living donor liver transplantation (LDLT) is usually multifactorial, but special attention is paid to the determination of donor liver volumes to minimize any risk of posthepatectomy liver failure (PHLF). Hepatobiliary scintigraphy (HBS) with single-photon-emission computed tomography allows for the measurement of total and future liver remnant function (FLR-F) and has been shown to predict the risk of PHLF more accurately than liver volumetry. Methods Since November 2016, HBS has been performed at our Institution in every candidate to major hepatectomy, including potential living liver donors. Results Thirty-seven consecutive patients were submitted to HBS, of whom 7 were potential living liver donors. After completed hepatectomy (n = 27), the median FLR-F of patients who developed PHLF (n = 9) was 1.72%/min/m2 (range 1.40–2.78) compared to that of patients who did not (n = 18), which was 4.02%/min/m2 (range 1.15–12.08). Three donors underwent operations (1 right hepatectomy and 2 left hepatectomies). In the only donor who developed PHLF, the FLR accounted for the 37% of the total liver volume, whereas the FLR represented only the 31% of the total liver function (TL-F = 11.29%/min) with a resulting FLR-F of 2.05%/min/m2. Conclusions The present study suggests that a non-invasive low-cost exam such as HBS may be a promising tool to predict PHLF not only in neoplastic patients but also to evaluate potential living donors. Larger studies are needed to draw any conclusion regarding the benefits of HBS in the living liver donor workup.

Aim: During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases. Materials and methods: We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma). Results: Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). Conclusion: Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

Prostate cancer is the most common cancer and the second leading cause of cancer death in men in the United States. Despite high prevalence, diagnosis and surveillance is limited due to indolent biology. Functional imaging techniques improved the ability to detect disease. Amino acids are building blocks of proteins and intracellular transport is upregulated in prostate cancer. Normal biodistribution patterns of fluciclovine include uptake in the liver and pancreas with minimal to no urine excretion, a distinct advantage for prostate cancer imaging. This review provides a detailed overview of the use of F-18 fluciclovine PET in prostate cancer imaging.

PURPOSE: Sensitive detection of cancer foci in men experiencing biochemical recurrence following initial treatment of prostate cancer is of great clinical significance with a possible impact on subsequent treatment choice. We describe a multisite experience of the efficacy and safety of the positron emission tomography/computerized tomography agent fluciclovine (18F) after biochemical recurrence. MATERIALS AND METHODS: A total of 596 patients underwent fluciclovine (18F) positron emission tomography/computerized tomography at 4 clinical sites. Detection rate determinations were stratified by the baseline prostate specific antigen value. Diagnostic performance was assessed against a histological reference standard in 143 scans. RESULTS: The subject level fluciclovine (18F) positron emission tomography/computer tomography detection rate was 67.7% (403 of 595 scans). Positive findings were detected in the prostate/bed and pelvic lymph node regions in 38.7% (232 of 599) and 32.6% of scans (194 of 596), respectively. Metastatic involvement outside the pelvis was detected in 26.2% of scans (155 of 591). The subject level detection rate in patients in the lowest quartile for baseline prostate specific antigen (0.79 ng/ml or less) was 41.4% (53 of 128). Of these patients 13 had involvement in the prostate/bed only, 16 had pelvic lymph node involvement without distant disease and 24 had distant metastases. The positive predictive value of fluciclovine (18F) positron emission tomography/computerized tomography scanning for all sampled lesions was 62.2%, and it was 92.3% and 71.8% for extraprostatic and prostate/bed involvement, respectively. Fluciclovine (18F) was well tolerated and the safety profile was not altered following repeat administration. CONCLUSIONS: Fluciclovine (18F) is well tolerated and able to detect local and distant prostate cancer recurrence across a wide range of prostate specific antigen values.

During COVID-19 outbreak (March 2020), a local 78-year-old male patient, with a history of treated non-Hodgkin lymphoma, was admitted to the hospital (day 1) with persistent fever, cough, and dyspnea. Thorax high-resolution computed tomography (HRCT) suspected viral lung infection and incidentally detected enlarged axillary and mediastinal lymphadenopathies. Reverse transcriptase-polymerase chain reaction (RTPCR) on pharyngeal swab yielded negative results for SARS-CoV-2 infection, both at patient admission and 2 days after (days 1 and 3). Subsequently (day 5), Streptococcus pneumoniae urinary antigen was found positive; therefore, the patient was immediately referred to high-dose antibiotics administration for pneumonia and to [18F]-FDG PET-CT for suspected lymphoma relapse. The scan (day 6) demonstrated multiple FDG avid lymphadenopathies above and below the diaphragm and increased diffuse uptake in the spleen in keeping with NHL progression and suspected bowel involvement. Furthermore, concomitant pneumonia was confirmed due to faint and diffuse uptake within a left inferior lobe consolidation and a single non-FDG-avid peripheral rounded ground-glass opacity (GGO) in the right upper lobe. A follow-up (day 11) HRCT demonstrated GGO small reduction, further extension of left basal consolidation, and new periscissural thickening in the right apex. Then, a third RT-PCR test (day 12) finally revealed COVID-19. Two weeks later, despite hydroxychloroquine and azithromycin, clinical and radiological worsening was documented (day 26) showing extensive interstitial viral involvement throughout both lungs. The patient started tocilizumab and required CPAP ventilation. Although RT-PCR remains the gold standard for COVID-19 diagnosis, false-negative/delayed results are not uncommon. The routine method for screening, diagnosis, and monitoring is HRCT. [18F]-FDG PET/CT is not specific, and differential diagnosis of lung infections is challenging [1–4]. According to this single experience, we suppose that co-infection with other pathogens (i.e., S. pneumoniae) might influence RT-PCR test accuracy; when clinical and CT features are highly suggestive for suspected COVID-19 pneumonia, precautions in patients management are recommended even in case of first RT-PCR negativities; during COVID-19 pandemic, incidental findings detected by a nuclear medicine physician at lung window CT component of PET/CT studies might be extremely relevant. [5]

Objectives: Visceral leishmaniasis (VL) is the most severe manifestation of the infection caused by the protozoan Leishmania, recently on increase in Italy and Spain. The aim of the study was to describe FDG uptake patterns in VL patients (pts) who underwent 18F-FDG PET/CT. Methods: A retrospective monocentric study of pts who underwent FDG PET/CT between 2008 and 2017 and later diagnosed with VL was performed. Semi-quantitative parameters were calculated in FDG-positive lesions: SUVmax, SUVmax spleen/SUVmax liver ratio (SLR), SUVmax focal/diffuse spleen ratio (FDR). Results: Overall, 23 pts were included. PET/CT was negative in 2 immunocompromised pts, positive in 21/23 (91%) [6 spleen only, 2 spleen + nodes, 7 spleen + bone marrow (BM), 4 spleen + BM + nodes, 1 spleen + BM + lung, 1 BM only + nodes, 2 nodes only]. Splenic involvement was demonstrated in 20/23 (87%) pts. Two different splenic patterns were observed: diffuse (13/20 pts, mean spleen SUVmax = 7.3 ± 4.2 [4.0–14.1], mean SLR = 2.2 ± 1.6 [1.3–6.7]) and focal over diffuse (7/20 pts, mean SUVmax = 12.6 ± 4.5 [9.5–20.5], mean SLR = 2.8 ± 0.8 [2.1–4.4], mean FDR = 2.1 ± 0.8 [1.2–3.6]). Extra-splenic FDG-avid findings were detected in 15/21 pts (65%): bone marrow in 13/15 (mean SUVmax = 4.0 ± 1.3 [2.8–6.0]), nodes in 67/15 and lung in 1/15. Conclusions: PET/CT demonstrated splenic FDG uptake in all immunocompetent VL pts; two splenic patterns (diffuse/focal over diffuse) were observed and indistinguishable from splenic involvement by other disorders. The most frequent extra-splenic FDG-positive sites were BM and lymph nodes. Considering the potential disease aggressiveness and recent outbreaks in north-eastern Italy, VL should be considered in the differential diagnosis of FDG-positive splenic findings in pts from endemic areas or reporting travels to endemic countries.

In this chapter cases of equivocal or difficult interpretation of FDG PET/CT in Multiple Myeloma are presented, including also IMPETUS criteria, to provide a base of knowledge for reporting the most common findings.

AIM: The aim of the study was to evaluate the visceral localization of the three most commonly used choline-based radiotracers (C-choline, F-methylcholine, and F-ethylcholine) with the aim of analyzing uptake in metabolically and anatomically disease-free patients. MATERIALS AND METHODS: A total of 1250 standardized uptake values (SUVmax, SUVmean) were analyzed in 45 anatomical regions in 45 patients (15 patients with C-choline, 15 with F-methylcholine, and 15 with F-ethylcholine). These patients were selected from a cohort of 3721 choline PET/computed tomography studies performed at three teaching hospitals over a period of 10 years. They had no evidence of metabolically active primary disease, metastatic disease, or altered morphology on the computed tomography component of the study or any evidence of disease elsewhere on other imaging modalities. The sites of primary disease (prostate and seminal vesicles) were excluded from evaluation. RESULTS: No adverse effect was documented when using the three tracers. Visceral localization was the same for all three tracers. Viscera with a statistical difference in intensity of uptake included the choroid plexus (P=0.0001), occipital lobe (P=0.014), parietal lobe (P=0.008), cerebellum (P=0.003), parotid gland (P=0.005), submandibular gland (P=0.001), tonsils (P=0.001), thyroid (P=0.0001), lungs (P=0.001), aorta (P=0.001), pulmonary artery (P=0.0001), liver segments I (P=0.005), III (P=0.005), IVB (P=0.03), and V (P=0.01), spleen [hilum (P=0.0009), body (P=0.0001)], pancreas [head (P=0.0001), body (P=0.01), tail (P=0.002)], esophagus (P=0.001), stomach (P=0.0001), duodenum (P=0.0002), large intestine (P=0.008), and rectum (P=0.0001). Elsewhere, no statistical difference was observed. Excreted activity was noted in the kidneys and bladder. CONCLUSION: This study demonstrates that the visceral localization of C-choline, F-methylcholine, and F-ethylcholine in disease-free patients is similar. Depending on the tracer uptake pattern, the viscera can be divided into two distinct categories: those with a statistically significant difference in uptake and those with no difference in uptake. The study outlines the range of SUVs for various organs for the three tracers and identifies some of the potential pitfalls in the evaluation of 'nonavid' but clinically significant presentation of different disease entities.

A significant number of patients radically treated for prostate cancer (PCa) will develop prostate-specific antigen recurrence (27-53%). Localizing the anatomical site of relapse is critical, in order to achieve the optimal treatment management. To date the diagnostic accuracy of standard imaging is low. Several desirable features have been identified for the amino-acid-based PET agent, fluciclovine (

A significant number of patients radically treated for prostate cancer (PCa) will develop prostate-specific antigen recurrence (27–53%). Localizing the anatomical site of relapse is critical, in order to achieve the optimal treatment management. To date the diagnostic accuracy of standard imaging is low. Several desirable features have been identified for the amino-acid-based PET agent, fluciclovine (18F) including: long 18F half-life which allows more practical use in centers without a cyclotron onsite; acting as a substrate for amino acid transporters upregulated in PCa or associated with malignant phenotype; lacking of incorporation into protein; and limited urinary excretion. Fluciclovine (18F) is currently approved both in USA and Europe with specific indication in adult men with suspected recurrent PCa based on elevated prostate-specific antigen following prior treatment.

Alterations of the cardiac autonomic nervous system play an important role in the pathway of many heart diseases. Nuclear imaging tools have been demonstrated to be useful for global and regional assessment of myocardial innervation. We used 11 C-meta-hydroxy-ephedrine ( 11 C-mHED), a catecholamine analogue, as a radiotracer usable with a PET/CT scanner to study the cardiac sympathetic system. After a fast and automatic synthesis of mHED and its labeling with 11 C, we acquired cardiac images by using a PET/ CT scanner. In this paper we present our preliminary results showing the radiotracer bio-distribution in humans 10 minutes post injection. The present study assesses the feasibility of PET/CT with the radiolabeled catecholamine analogue ( 11 C-mHED) in order to determine sympathetic innervation in the human heart.

Recently new radiopharmaceuticals have been proposed for investigating prostate cancer patients, including metabolic radiotracer such as anti1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (18F-FACBC) or probe targeting the prostate-specific membrane antigen (PSMA). These radiotracers showed in literature better performance in the detection of prostate cancer recurrence as compared to choline PET/CT imaging [1, 2].

Positron emission tomography (PET) is a sectional molecular imaging procedure that allows evaluation of the metabolism at a molecular and cellular level. For a PET scan, the patient is injected with a radiotracer, such as (18)F-fluorodeoxyglucose (FDG). FDG PET-computed tomography has become an established modality for metabolic staging and plays an important role in the major steps of evaluation and treatment of most lymphoma subtypes, with significant impact in the initial staging, posttherapy evaluation, and suspect of relapse of disease. However, whenever the information of PET results is translated to changing treatment, especially in cases of further treatment, biopsy confirmation should always be made when possible.

PURPOSE: We present findings concerning (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) at end-treatment evaluation in follicular lymphoma (FL) in order to establish possible predictive factors for progression-free survival (PFS) and patient outcome. METHODS: We retrospectively analysed data from 91 consecutive FL patients (M:F = 51:40, mean age 61) referred to our PET Unit at therapy completion: 38 with an indolent form (grade 1-2) and 53 with an aggressive FL (grade 3a and b) according to the World Health Organization (WHO) classification. A total of 148 FDG PET/CT scans were analysed and findings reported as positive or negative for disease. The overall response to treatment was assessed according to the revised International Workshop Criteria (IWC). The final outcome was defined as remission or disease by taking clinical, instrumental and histological data as standards of reference, with a mean follow-up period of 3 years (range 1-8). A statistical analysis was performed with respect to PFS and patient outcome for FDG PET result, tumour grading, Follicular Lymphoma International Prognostic Index (FLIPI), disease stage and number of relapses, on uni- and multivariate analyses, with p < 0.05 considered as significant. RESULTS: Overall patients presented a mean PFS of 35 months (range 3-86), with a relapse rate of 42%. At final outcome, remission was achieved in 67 of 91 patients (74%). Of the different predictive factors, only FDG PET result significantly correlated with patient outcome (p = 0.0002). PET/CT performance at the end of treatment was as follows: 100% sensitivity, 99% specificity, 89% positive predictive value and 100% negative predictive value. The Kaplan-Meier analysis demonstrated a statistically significant correlation with PFS for FDG PET (p < 0.0001), FLIPI score (0-1 versus ≥ 2) (p = 0.0451) and number of relapses (none versus ≥ 1) (p = 0.0058). These findings were confirmed at the univariate analysis, whereas at the multivariate analysis only FDG PET (p = 0.0006892) and number of relapses (p = 0.01947) were independent predictive factors for PFS. CONCLUSION: End-treatment PET/CT in FL has high accuracy and appears to be a good predictor of PFS and patient outcome, irrespective of grading. As expected, patients facing more than one relapse seem to have significantly shorter PFS in the presence of a positive FDG PET.

A patient multiple endocrine neoplasia type 1 presenting with radiological suspicion of pancreatic neuroendocrine tumor relapse after surgical and somatostatin analog treatment underwent restaging Ga-DOTANOC PET/CT. Standard and delayed images detected an area of focal intense uptake moving from the left para-aortic to the paracaval region. The lesion was identified at previous imaging in different abdominal locations (eg, adjacent to the duodenal wall at presurgical PET and in the aortocaval region at restaging contrast-enhanced CT). Dual time-point Ga-DOTANOC PET/CT was crucial to accurately diagnose the wandering mesenteric lymph node, a potential interpretation pitfall especially when found far from the initial position.

Deregulated cell cycle progression is a hallmark of cancer [1, 2]. The majority of therapeutic drugs have been designed to inhibit cell proliferation and/or to induce apoptosis. Metabolic imaging with positron emission tomography (PET) and the glucose analog 2′-[18F]fluoro-2′-deoxyglucose (18F-FDG) is a sensitive imaging modality to detect malignant tumors and to identify response to therapy early in the course of anticancer treatment [3, 4].18F-FDG is also a valuable clinical tool for predicting tumor response to therapy and patient survival [5, 6]. However, tumoral uptake of 18F-FDG is a biomarker of glucose metabolism and is associated with false positive findings in inflammatory processes [7, 8].

PURPOSE: To compare the accuracy of 18F-FACBC and 11C-choline PET/CT in patients radically treated for prostate cancer presenting with biochemical relapse. METHODS: This prospective study enrolled 100 consecutive patients radically treated for prostate cancer and presenting with rising PSA. Of these 100 patients, 89 were included in the analysis. All had biochemical relapse after radical prostatectomy (at least 3 months previously), had 11C-choline and 18F-FACBC PET/CT performed within 1 week and were off hormonal therapy at the time of the scans. The two tracers were compared directly in terms of overall positivity/negativity on both a per-patient basis and a per-site basis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for both the tracers; follow-up at 1 year (including correlative imaging, PSA trend and pathology when available) was considered as the standard of reference. RESULTS: In 51 patients the results were negative and in 25 patients positive with both the tracers, in eight patients the results were positive with 18F-FACBC but negative with 11C-choline, and in five patients the results were positive with 11C-choline but negative with 18F-FACBC. Overall in 49 patients the results were false-negative (FN), in two true-negative, in 24 true-positive (TP) and in none false-positive (FP) with both tracers. In terms of discordances between the tracers: (1) in one patient, the result was FN with 11C-choline but FP with 18F-FACBC (lymph node), (2) in seven, FN with 11C-choline but TP with 18F-FACBC (lymph node in five, bone in one, local relapse in one), (3) in one, FP with 11C-choline (lymph node) but TP with 18F-FACBC (local relapse), (4) in two, FP with 11C-choline (lymph nodes in one, local relapse in one) but FN with 18F-FACBC, and (5) in three, TP with 11C-choline (lymph nodes in two, bone in one) but FN with 18F-FACBC. With 11C-choline and 18F-FACBC, sensitivities were 32 % and 37 %, specificities 40 % and 67 %, accuracies 32 % and 38 %, PPVs 90 % and 97 %, and NPVs 3 % and 4 %, respectively. Categorizing patients by PSA level (