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

FDG-PET/CT is a standardized imaging technique that has reached a great importance in the management of patients affected by Multiple Myeloma. It is proved, in fact, that it allows a deep evaluation of therapy efficacy and provides several prognostic indexes both at staging and after therapy. For this reason, it is now recognised as a gold standard for therapy assessment. Beside this, in reacent years FDG-PET/CT contribution to the understanding of Multiple Myeloma has progressively grown. Papers have been published analyzing the prognostic value of active disease volume measurement and standardization issues, the meaning of FDG positive paramedullary and extrameduallary disease, the prognostic impact of FDG positive minimal residual disease, the relation between focal lesions and clonal eterogenity of this disease and the comparison with whole body DWI-MR in terms of detection and therapy assessment. These newer aspects not of clinical impact yet, of FDG-PET/CT in Multiple Myeloma will be presented and discussed in this review.

Sarcoma represents less than 2% of adult malignancies and about 15% to 20% of malignancies in children and adolescents/young adults. This neoplasm accounts for more than 80 different clinico-pathological entities with different clinical behavior; osteosarcoma and ewing sarcoma are the most frequent primary bone tumors. Because of the general poor prognosis, it is important to find out as many prognostic factors as possible to choose the best therapeutical approach and to correctly schedule the follow-up examinations. Third level imaging such as MRI and PET/CT are of utmost importance in the evaluation of sarcoma patients. The spine and bones in general are optimal sites to be evaluated with FDG PET/CT since the physiological background is low. The standardized uptake value (SUV max, a semiquantitave parameter) is used as a surrogate for proliferative cell rate, and the spatial heterogeneity of FDG distribution within the primary mass as a surrogate for malignancy. In several studies SUVmax was a predictive value for overall survival and progression-free survival. Whole-body MRI is a well-established technique for systemic, radiation-free evaluation, which is mostly applied in the oncological field. WB-MRI provides a combination of anatomical and functional sequences and is useful specifically in the evaluation of disease in organs with relatively high background activity such as the brain, liver, kidney, and spinal canal. These technologies provide accurate staging (also useful to drive the biopsy towards the most active foci in large heterogeneous masses), therapy assessment, relapse detection of local recurrence and distance metastasis but also prognostic indexes, in the context of whole body diagnostic procedures. This paper will provide an overview of the role and added value of PET/CT and WB-MRI in bone sarcomas particular focus on osteosarcoma. We also analyzed the role of the PET/CT and MRI for target delineation of radiation therapy and we and we will do an analysis of future prospects as new tracer non FDG.

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.

Fluorodeoxyglucose-PET/CT is a valuable tool for the work-up of patients with newly diagnosed and relapsed/refractory multiple myeloma, because it assesses bone damage with high sensitivity and specificity and detects extramedullary sites of proliferating clonal plasma cells (extramedullary diseases). PET/CT provides valuable prognostic data at diagnosis and at restaging during the course of the disease. Consistencies between independent studies confirm the negative prognostic value of extramedullary disease and greater than 3 focal lesions, whereas the role of standardized uptake value is more conflicting. Standardization of the technique is ongoing.

Soft tissue sarcomas (STS) are highly fluorine-18-fluorodeoxyglucose (F-FDG)-avid tumours. PET seems to be effective for the assessment of the extent of disease. However, the use of PET to stratify STS into different risk histotypes still remains controversial. Our aim was to evaluate F-FDG uptake in different STS types and to assess the prognostic value of the maximum standardized uptake value (SUVmax).We reviewed 50 adult patients with primary high-grade STS of the extremities with a preoperative PET. Overall survival and local recurrence were analysed.The mean SUVmax was 12.9 (range: 2.2-33.4). All cases of myxoid liposarcoma and all cases of synovial sarcoma had SUVmax of less than 10.3. A better overall survival and local recurrence were observed in patients with SUVmax of less than 10.3 (P=0.005 and 0.046, respectively).SUVmax seems to be specific among different STS histotypes. PET does not seem to be useful in myxoid liposarcoma as well as synovial sarcoma as these tumours seem to have a low uptake of glucose. SUVmax might also be included as a prognostic factor.

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.

International audience; Purpose: Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is included in the International Myeloma Working Group (IMWG) imaging guidelines for the work-up at diagnosis and the follow-up of multiple myeloma (MM) notably because it is a reliable tool as a predictor of prognosis. Nevertheless, none of the published studies focusing on the prognostic value of PET-derived features at baseline consider tumor heterogeneity, which could be of high importance in MM. The aim of this study was to evaluate the prognostic value of baseline PET-derived features in transplant-eligible newly diagnosed (TEND) MM patients enrolled in two prospective independent European randomized phase III trials using an innovative statistical random survival forest (RSF) approach.Methods: Imaging ancillary studies of IFM/DFCI2009 and EMN02/HO95 trials formed part of the present analysis (IMAJEM and EMN02/HO95, respectively). Among all patients initially enrolled in these studies, those with a positive baseline FDG-PET/CT imaging and focal bone lesions (FLs) and/or extramedullary disease (EMD) were included in the present analysis. A total of 17 image features (visual and quantitative, reflecting whole imaging characteristics) and 5 clinical/histopathological parameters were collected. The statistical analysis was conducted using two RSF approaches (train/validation + test and additional nested cross-validation) to predict progression-free survival (PFS).Results: One hundred thirty-nine patients were considered for this study. The final model based on the first RSF (train/validation + test) approach selected 3 features (treatment arm, hemoglobin, and SUVmaxBone Marrow (BM)) among the 22 involved initially, and two risk groups of patients (good and poor prognosis) could be defined with a mean hazard ratio of 4.3 ± 1.5 and a mean log-rank p value of 0.01 ± 0.01. The additional RSF (nested cross-validation) analysis highlighted the robustness of the proposed model across different splits of the dataset. Indeed, the first features selected using the train/validation + test approach remained the first ones over the folds with the nested approach.Conclusion: We proposed a new prognosis model for TEND MM patients at diagnosis based on two RSF approaches.Trial registration: IMAJEM: NCT01309334 and EMN02/HO95: NCT01134484.

During the past 10 years, performing real-time molecular imaging with positron emission tomography (PET) in combination with computed tomography (CT) during interventional procedures has undergone rapid development. Keeping in mind the interest of the nuclear medicine readers, an update is provided of the current workflows using real-time PET/CT in percutaneous biopsies and tumor ablations. The clinical utility of PET/CT guided biopsies in cancer patients with lung, liver, lymphoma, and bone tumors are reviewed. Several technological developments, including the introduction of new PET tracers and robotic arms as well as opportunities provided through acquiring radioactive biopsy specimens are briefly reviewed.

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 According to published data, radiomics features differ between lesions of refractory/relapsing HL patients from those of long-term responders. However, several methodological aspects have not been elucidated yet. Purpose The study aimed at setting up a methodological framework in radiomics applications in Hodgkin’s lymphoma (HL), especially at (a) developing a novel feature selection approach, (b) evaluating radiomic intra-patient lesions’ similarity, and (c) classifying relapsing refractory (R/R) vs non-(R/R) patients. Methods We retrospectively included 85 patients (male:female = 52:33; median age 35 years, range 19–74). LIFEx (www.lifexsoft.org) was used for [18F]FDG-PET/CT segmentation and feature extraction. Features were a-priori selected if they were highly correlated or uncorrelated to the volume. Principal component analysis-transformed features were used to build the fingerprints that were tested to assess lesions’ similarity, using the silhouette. For intra-patient similarity analysis, we used patients having multiple lesions only. To classify patients as non-R/R and R/R, the fingerprint considering one single lesion (fingerprint_One) and all lesions (fingerprint_All) was tested using Random Undersampling Boosting of Tree Ensemble (RUBTE). Results HL fingerprints included up to 15 features. Intra-patient lesion similarity analysis resulted in mean/median silhouette values below 0.5 (low similarity especially in the non-R/R group). In the test set, the fingerprint_One classification accuracy was 62% (78% sensitivity and 53% specificity); the classification by RUBTE using fingerprint_All resulted in 82% accuracy (70% sensitivity and 88% specificity). Conclusions Lesion similarity analysis was developed, and it allowed to demonstrate that HL lesions were not homogeneous within patients in terms of radiomics signature. Therefore, a random target lesion selection should not be adopted for radiomics applications. Moreover, the classifier to predict R/R vs non-R/R performed the best when all the lesions were used.

Due to the increasing life expectancy, the diagnosis of malignancy and treatment of elderly patients is becoming more common. Prostate cancer is particularly frequent in this setting. Many different approaches are now available, but some of them imply significant risks or collateral effects. In those patients an accurate evaluation of risk-to-benefit ratio is needed, and functional imaging such as PET/CT is important for the clinician to make the appropriate choice. PET/CT in prostate cancer is a well-tolerated procedure that can be used to accurately assess the tumor extent during the entire clinical history of the disease. Nowadays there are several available radiopharmaceuticals for prostate cancer PET/CT imaging, each one with specific advantages and disadvantages. The two most promising and more widely employed in the clinical setting are 18F-Flucyclovine and 68Ga-PSMA. This paper will provide an overview of these two tracers for imaging prostate cancer in elderly patients.

Purpose: 18F-FDG PET/CT is an emerging technique for diagnosis of cardiac implantable electronic devices infection (CIEDI). Despite the improvements in transvenous lead extraction (TLE), long-term survival in patients with CIEDI is poor. The aim of the present study was to evaluate whether the extension of CIEDI at 18F-FDG PET/CT can improve prediction of survival after TLE. Methods: Prospective, monocentric observational study enrolling consecutive candidates to TLE for a diagnosis of CIEDI. 18F-FDG PET/CT was performed in all patients prior TLE. Results: There were 105 consecutive patients with confirmed CIEDI enrolled. An increased 18F-FDG uptake was limited to cardiac implantable electrical device (CIED) pocket in 56 patients, 40 patients had a systemic involvement. We had nine negative PET in patients undergoing prolonged antimicrobial therapy (22.5 ± 14.0days vs. 8.6 ± 13.0days; p = 0.005). Implementation of 18F-FDG PET/CT in modified Duke Criteria lead to reclassification of 23.8% of the patients. After a mean follow-up of 25.0 ± 9.0months, 31 patients died (29.5%). Patients with CIED pocket involvement at 18F-FDG PET/CT presented a better survival independently of presence/absence of systemic involvement (HR 0.493, 95%CI 0.240–0.984; p = 0.048). After integration of 18F-FDG PET/CT data, absence of overt/hidden pocket involvement in CIEDI and a (glomerular filtration rate) GFR < 60ml/min were the only independent predictors of mortality at long term. Conclusions: Patient with CIEDI and a Cold Closed Pocket (i.e., a CIED pocket without skin erosion/perforation nor increased capitation at 18F-FDG PET/CT) present worse long-term survival. Patient management can benefit by systematic adoption of pre-TLE 18F-FDG PET/CT through improved identification of CIED related endocarditis (CIEDIE) and hidden involvement of CIED pocket.

PURPOSE: To investigate the prognostic value of posttreatment 18F-FDG PET/CT in patients with locally advanced cervical cancer (LACC) treated with concomitant chemoradiation therapy (CCRT). The secondary aim was to assess the possible role of intensity-based and volume-based PET parameters including SUVmax, SUVmean, MTV and TLG, and clinical parameters including age, pathology, FIGO stage and nodal involvement as factors predicting response to treatment. METHODS: This retrospective study included 82 patients affected by LACC treated with CCRT. All patients underwent 18F-FDG PET/CT both before and after treatment. The posttreatment PET/CT scans were used to classify patients as complete metabolic responders (CMR) or non-complete metabolic responders (N-CMR) according to the EORTC criteria. Kaplan-Meier analysis was used to evaluate differences in overall survival (OS) between the CMR and N-CMR groups. Student's t test, Pearson's chi-squared test and logistic regression were used to investigate the possible value of PET and clinical parameters as predictors of metabolic response to therapy. RESULTS: Kaplan-Meier analysis showed a highly significant difference in OS between the CMR and N-CMR groups (log-rank test p

FDG PET/CT (18F-fluoro-deoxy-glucose positron emission tomography/computed tomography) is a useful tool to image multiple myeloma (MM). However, simple and reproducible reporting criteria are still lacking and there is the need for harmonization. Recently, a group of Italian nuclear medicine experts defined new visual descriptive criteria (Italian Myeloma criteria for Pet Use: IMPeTUs) to standardize FDG PET/CT evaluation in MM patients. The aim of this study was to assess IMPeTUs reproducibility on a large prospective cohort of MM patients. MATERIALS AND METHODS: Patients affected by symptomatic MM who had performed an FDG PET/CT at baseline (PET0), after induction (PET-AI), and the end of treatment (PET-EoT) were prospectively enrolled in a multicenter trial (EMN02)(NCT01910987; MMY3033). After anonymization, PET images were uploaded in the web platform WIDEN® and hence distributed to five expert nuclear medicine reviewers for a blinded independent central review according to the IMPeTUs criteria. Consensus among reviewers was measured by the percentage of agreement and the Krippendorff's alpha. Furthermore, on a patient-based analysis, the concordance among all the reviewers in terms of positivity or negativity of the FDG PET/CT scan was tested for different thresholds of positivity (Deauville score (DS 2, 3, 4, 5) for the main parameters (bone marrow, focal score, extra-medullary disease). RESULTS: Eighty-six patients (211 FDG PET/CT scans) were included in this analysis. Median patient age was 58 years (range, 35-66 years), 45% were male, 15% of them were in stage ISS (International Staging System) III, and 42% had high-risk cytogenetics. The percentage agreement was superior to 75% for all the time points, reaching 100% of agreement in assessing the presence skull lesions after therapy. Comparable results were obtained when the agreement analysis was performed using the Krippendorff's alpha coefficient, either in every single time point of scanning (PET0, PET-AI or PET-EoT) or overall for all the scans together. DS proved highly reproducible with the highest reproducibility for score 4. CONCLUSIONS: IMPeTUs criteria proved highly reproducible and could therefore be considered as a base for harmonizing PET interpretation in multiple myeloma. A prospective clinical validation of IMPeTUs criteria is underway.

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.

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

Introduction Biopsy of affected tissue is required for lymphoma diagnosis and to plan treatment. Open incisional biopsy is traditionally the method of choice. Nevertheless, it requires hospitalization, availability of an operating room, and sometimes general anesthesia, and it is associated with several drawbacks. Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) can be potentially used to drive biopsy to the most metabolically active area within a lymph node or extranodal masses. Methods A study of diagnostic accuracy was conducted to assess the performance of a PET-driven needle biopsy in patients with suspect active lymphoma. Results Overall, 99 procedures have been performed: three (3.0%) were interrupted because of pain but were successfully repeated in two cases. Median SUVmax of target lesions was 10.7. In 84/96 cases, the tissue was considered adequate to formulate a diagnosis (diagnostic yield of 87.5%) and to guide the following clinical decision. The target specimen was a lymph node in 60 cases and an extranodal site in 36. No serious adverse events occurred. The sensitivity of this procedure was 96%, with a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 75%. Conclusion Patients can benefit from a minimally invasive procedure which allows a timely and accurate diagnosis of lymphoma at onset or relapse.

Conventional imaging of prostate cancer has limitations related to the frequently indolent biology of the disease. PET is a functional imaging method that can exploit various aspects of tumor biology to enable greater detection of prostate cancer than can be provided by morphologic imaging alone. Radiotracers that are in use or under investigation for targeting salient features of prostate cancer include those directed to glucose, choline, acetate, prostate-specific membrane antigen, bombesin, and amino acids. The tumor imaging features of this last class of radiotracers mirror the upregulation of transmembrane amino acid transport that is necessary in carcinomas because of increased amino acid use for energy requirements and protein synthesis. Natural and synthetic amino acids radiolabeled for PET imaging have been investigated in prostate cancer patients. Early work with naturally occurring amino acid-derived radiotracers, such as L-C-11-methionine and L-1-C-11-5-hydroxytryptophan, demonstrated promising results, including greater sensitivity than F-18-FDG for intraprostatic and extraprostatic cancer detection. However, limitations with naturally occurring amino acid-derived compounds, including metabolism of the radiotracer itself, led to the development of synthetic amino acid radiotracers, which are not metabolized and therefore more accurately reflect transmembrane amino acid transport. Of the synthetic amino acid-derived PET radiotracers, anti-1-amino-3-F-18-fluorocyclobutane-1-carboxylic acid (F-18-FACBC or F-18-fluciclovine) has undergone the most promising translation to human use, including the availability of simplified radiosynthesis. Several studies have indicated advantageous biodistribution in the abdomen and pelvis with little renal excretion and bladder activity characteristics beneficial for prostate cancer imaging. Studies have demonstrated improved lesion detection and diagnostic performance of 18F-fluciclovine in comparison with conventional imaging, especially for recurrent prostate cancer, although issues with nonspecific uptake limit the potential role of F-18-fluciclovine in the diagnosis of primary prostate cancer. Although work is ongoing, recently published intrapatient comparisons of F-18-fluciclovine with C-11-choline reported higher overall diagnostic performance of the former, especially for the detection of disease relapse. This review is aimed at providing a detailed overview of amino acid-derived PET compounds that have been studied for use in prostate cancer imaging.

This article presents fluorodeoxyglucose PET/computed tomography for the evaluation of soft tissue sarcomas. Its clinical impact is discussed analyzing all the clinical information provided when applied in different phases of the disease. A special paragraph is dedicated to the use of functional imaging for driving the biopsy.

The identification of bone lesions and extramedullary disease is crucial in the diagnosis of myeloma. Whole-body X-ray (WBXR) is considered the gold standard for the detection of myeloma bone lesions. Nevertheless, the International Myeloma Working Group recently updated the disease definition and emphasised the value of magnetic resonance imaging (MRI), computed tomography (CT) alone or combined with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). The presence of more than one focal lesion with MRI or the presence of one or more lytic bone lesion with CT (including low dose CT alone or combined with FDG PET) is considered as myeloma defining events (if 5 mm or more in size). Due to its higher sensitivity to detect bone lesions (in comparison with WBXR), MRI of spine and pelvis is mandatory for patients with solitary plasmacytoma as additional bone lesions can be detected in approximately one-third of cases. MRI is also recommended in patients with smouldering myeloma and may be considered for the staging of multiple myeloma (MM). Moreover, accurate imaging of MM and related plasma cell disorders using MRI and/or FDG PET/CT may provide information on tumour burden, aggressiveness and tumour heterogeneity. Nonetheless, inclusion of MRI and FDG PET/CT for MM patient stratification and therapeutic decisions remains to define.

Primary angiosarcoma of the bone (PAB) is a particularly rare and aggressive form of malignancy in the spectrum of vascular tumours, and it accounts for less than 1% of sarcomas. This case of PAB, diagnosed thanks to FDG-PET/CT guided biopsy, is a paradigm of how powerful are clinical informations that can be derived by a F-FDG PET/CT, in view of negative or inconclusive imaging of conventional radiology, starting from the metabolic characterization of an equivocal finding, the possibility to drive the biopsy towards the most active site, the accurate total body staging, the stratification of prognosis and early therapy assessment.

Dysfunction of the sympathetic nervous system underlies many cardiac diseases and can be assessed by molecular imaging using SPECT tracers as I-metaiodobenzylguanidine (I-MIBG). The norepinephrine analog C-meta-hydroxyephedrine (HED) has been used with PET to map the regional distribution of cardiac sympathetic neurons. Hydroxyephedrine is rapidly transported into sympathetic neurons by the norepinephrine transporter and stored in vesicles. This review describes the mechanism of action, radiosynthesis, and application of HED in the assessment of the cardiac sympathetic nervous system in heart failure, myocardial infarction, and arrhythmias. Noncardiac applications of HED in the clinical setting of sympathetic nervous system tumors and other emerging research applications are described.

Background Only about 1% of all head and neck lateral or paramedian cancers described in the scientific literature shows, in staging, contralateral cervical adenopathy without ipsilateral pathological involvement of lymph nodes. Case Presentation This case is one of them, in which 18F–FDG PET/CT scan is confirmed by pathology findings, and has correctly identified all metastatic disease foci. Conclusions To date, PET/CT is not recommended in head and neck cancer staging. However, the use of PET/CT in head and neck cancer staging can define possible metastatic disease foci, clarify c.e. CT suspicious findings and, in some cases, change the TNM stage, with a strong prognostic and therapeutic impact.

Background Unilateral condylar hyperplasia (UCH) of the mandible, or Hypercondylia, is a pathological condition that determines an abnormal growth of the affected condyle. Bone SPECT with Tc99m-diphosphonates is a successful tool in the diagnosis of UCH. EANM guidelines also suggest the use of 18F–NaF PET/CT, though it leads to a higher radiation exposure. Aim As UCH patients are young, we aimed to develop a low dose 18F–Fluoride PET/CT protocol and compare it to a standard injected activity scan, to assess if the image quality remains unchanged. Materials and methods We prospectively enrolled 20 patients (7 males, 13 females, mean age 23.2) with UCH, who underwent 18F–NaF PET/CT to assess the hypercondylia. We administered a low activity of 18F–NaF (2.9 MBq/kg) in 15 patients and a standard activity (5.3 MBq/kg) in 5 patients. Activity range was chosen according to 2015 EANM guidelines. To determine if the scans with low radiotracer activity were “diagnostic” such as those with standard activity, two expert nuclear medicine physicians, unaware of the administered activity, independently reviewed the scans and expressed a final qualitative judgment in terms of “diagnostic”/“non-diagnostic” scan. Furthermore, we compared the effective dose of a low injected activity PET/CT to the standard one and to a Bone SPECT performed with standard injected activity of Tc99m-diphosphonates. Results Reviewers classified 19 of 20 scans as “diagnostic”. Only one of them was classified as “non diagnostic” due to condylar arthrosis that disturbed the correct evaluation of condylar radiotracer uptake. The effective dose of a 18F–Fluoride PET/CT, in patient of 70 kg, is about 3.5 mSv in scans performed with 2.9 MBq/kg [0.017 mSv/MBq × 2.9 MBq/kg × 70 kg] and about 6.3 mSv in ones performed with 5.3 MBq/kg [0.017 mSv/MBq × 5.3 MBq/kg × 70 kg]. The effective dose of 99mTc-MDP bone SPECT is about 3.2 mSv [0.0043 mSv/MBq × 740 MBq of 99mTc-MDP]. Discussion 18F–NaF PET/CT performed with a low radiotracer activity allows a good assessment of UCH similar to that performed with an ordinary activity. The effective radiation dose of a low-injected activity PET/CT is significantly lower than an ordinary-injected activity and is not significantly higher than the most used Bone SPECT. Moreover PET/CT is performed in 1.5 h while Bone SPECT requires at least 3.5 h. Conclusions The 18F–Fluoride PET/CT procedure could be performed with 2.9 MBq/Kg (minimum 185 MBq, recommended at least 200 MBq) of 18F–NaF to minimize the effective radiation dose received, maintaining the quality of the scan. Further studies including a larger number of patients and clinical follow-up are needed to confirm our preliminary findings.

Multiple myeloma is a plasma cell dyscrasia producing bone lytic lesions. In recent years, a wide spectrum of therapeutic approaches are available to treat the disease: an accurate therapy assessment has, therefore, become of utmost importance.In this field, imaging is becoming a cornerstone, especially in association with clinical parameters. Among imaging procedures, FDG PET/CT is recognized to provide reliable information, achieved in a very safe and fast procedure.The literature has produced very concordant results from different groups assessing the value of FDG PET/CT as a prognostic factor in general and in therapy assessment, but some issues remain regarding a standardization of image interpretation especially in borderline cases.So far, no data regarding nor other imaging compounds and the use of hybrid tomographs PET/MR are available to define therapy assessment in PET.

The objective of this study is to compare the most recent systems for the staging of multiple myeloma (MM), the Durie-Salmon PLUS system and the International Staging System, according to patients' survival rates and response to therapy. Another objective is to verify whether patterns of bone marrow alteration on MRI (i.e., focal, diffuse, or variegated patterns) can provide prognostic information for patients with MM.We retrospectively enrolled 85 patients with MM who were monitored for a minimum of 6 years and who underwent contrast-enhanced spinal and pelvic MRI at 1.5 T and whole-body FDG PET/CT at the time of diagnosis. Patients underwent MM staging performed using both staging systems and were divided into groups on the basis of their MRI patterns. These patient groups were then compared in terms of survival, response to therapy, and duration of response.Both staging systems showed great capability in differentiating patients with a worse prognosis from patients with a better outcome, with the capability of both systems found to be statistically significant, albeit less statistically significant for the Durie-Salmon PLUS system (p = 0.010 vs p = 0.046, respectively). Patients with a focal pattern on MRI had a worse survival rate than did the patients with other MRI patterns (p = 0.032).These data indicate that both the International Staging System and the Durie-Salmon PLUS system have great potential for characterizing and stratifying MM to determine the survival outcome and therapy response of patients. Observation of a focal pattern on MRI seems to be associated with poorer survival.

Purpose: To evaluate the relationship between aortic inflammation as assessed by18F–fluorodeoxyglucose-positron emission tomography (18F–FDG-PET) and features of plaque vulnerability as assessed by frequency domain-optical coherence tomography (FD-OCT). Methods: We enrolled 30 consecutive non-ST-segment elevation acute coronary syndrome patients undergoing percutaneous coronary intervention. All patients underwent three-vessel OCT before intervention and18F–FDG-PET before discharge. Univariable and C-reactive protein (CRP)-adjusted linear regression analyses were performed between features of vulnerability [namely:lipid-rich plaques with and without macrophages and thin cap fibroatheromas (TCFA)] and18F–FDG uptake in both ascending (AA) and descending aorta (DA) [measured either as averaged mean and maximum target-to-blood ratio (TBR) or as active slices (TBRmax ≥ 1.6)]. Results: Mean age was 62 years, and 26 patients were male. On univariable linear regression analysis TBRmeanand TBRmaxin DA was associated with the number of lipid-rich plaques (β = 4.22; 95%CI 0.05–8.39; p = 0.047 and β = 3.72; 95%CI 1.14–6.30; p = 0.006, respectively). TBRmaxin DA was also associated with the number of lipid-rich plaques containing macrophages (β = 2.40; 95%CI 0.07–4.72; p = 0.044). A significant CRP adjusted linear association between the TBRmaxin DA and the number of lipid-rich plaques was observed (CRP-adjusted β = 3.58; 95%CI -0.91-6.25; p = 0.01). TBRmaxin DA showed a trend towards significant CRP-adjusted association with number of lipid-rich plaques with macrophages (CRP-adjusted β = 2.30; 95%CI -0.11-4.71; p = 0.06). We also observed a CRP-adjusted (β = 2.34; 95%CI 0.22–4.47; p = 0.031) linear association between the number of active slices in DA and the number of lipid-rich plaques. No relation was found between FDG uptake in the aorta and the number of TCFAs. Conclusions: In patients with first NSTEACS, 18F–FDG uptake in DA is correlated with the number of OCT detected lipid-rich plaques with or without macrophages. This association may be independent from CRP values.

When an intense intestinal FDG accumulation occurs, especially if focal, it can be referred to either physiological intestinal activity or bowel disease, thus leading to a radical change in patient's prognosis. Within a year, we recommended a colonoscopy to 103 of 7365 patients who were subjected to a total body FDG PET/CT. In a case-series study, we re-evaluated the patients and their lesions if already investigated with colonoscopy and biopsy. Only 18 patients were included in our study, but in none of them biopsy was negative and 3 adenocarcinomas, 8 adenomas, 5 inflammatory patterns, 1 hyperplastic polyp and 1 eosinophilic infiltrate were diagnosed. In 16 patients, no suspicion was present and diagnosis was absolutely incidental. Besides, among the three major groups (adenocarcinomas, adenomas and phlogosis), SUVmax values were significantly different. Adenocarcinomas are linked with high SUVmax values (ranging from 8.3 to 20.2) and large size (ranging from 26 to 43 mm). PET/CT sensitivity is low in detecting adenomas, being 71.4% if they are larger than 6 mm and 50% if SUVmax is lower than 4.9. SUVmax values in inflammatory lesions can range from 5.7 to 12. Colorectal cancer is still the second leading cause of cancer death, for this reason in many countries screening programs have been approved and colonoscopy is considered the golden standard. PET/CT cannot be considered as a screening test, but if it incidentally reveals intestinal abnormalities, this data cannot be underestimated and colonoscopy is highly recommended.

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.

Liver nodules are common findings in medical practice, both in patients with and in those without chronic liver disease. These lesions have to be interpreted according to clinical history and biochemical findings. Conventional imaging (US, CT and MRI) is still the gold standard for evaluating liver nodules, while diagnostic flowcharts do not currently include PET/CT. Since the 1990s many studies have been conducted to assess a possible role for FDG PET or PET/CT in several liver pathologies. According to the literature, FDG PET (and later PET/CT) could be useful in detecting, staging and grading hepatocellular carcinoma, often leading to a change in therapy, and may even detect intrahepatic cholangiocarcinoma with adequate sensitivity. Moreover, FDG can allow more accurate staging of hepatic involvement deriving from other tumors (often underestimated by conventional imaging) and, therefore, more appropriate therapy in affected patients. Finally, FDG PET can also be used to evaluate 90Y microsphere therapy response. Other conditions (e.g., primary hepatic lymphoma when conventional imaging is inconclusive) may benefit from the use of FDG PET/CT, while benign lesions (e.g., focal nodular hyperplasia) show low FDG avidity. As regards non-FDG tracers, choline and acetate (ACE) have been evaluated in comparison with FDG and found to show good efficacy in detecting and staging well- or moderately differentiated HCC. However, their sensitivity in poorly differentiated HCC is very low, suggesting that dual-tracer investigation (FDG and choline/FDG and ACE) could be useful when non-invasive grading is required. Despite promising results, PET evaluation of liver nodules still seems to be far from routine application, mostly because of cost-related issues.

PURPOSE: This study aims to evaluate the role of (11)C-choline PET/CT in patients with biochemical relapse after radical prostatectomy (RP) showing prostate-specific antigen (PSA) values lower than 0.5 ng/mL. METHODS: We performed (11)C-choline PET/CT in 71 consecutive patients previously treated with RP showing PSA values lower than 0.5 ng/mL. (11)C-Choline PET/CT was performed following standard procedure. (11)C-Choline PET/CT-positive findings were validated by transrectal ultrasonography + biopsy, repeated (11)C-choline PET/CT, other conventional imaging modality, and histology. RESULTS: (11)C-Choline PET/CT was true positive in 15/71 (21.1%). (11)C-Choline uptake was observed in pelvic lymph nodes (7/71; 9.9%), in the prostatic bed (7/71; 9.9%), and in bone (1/71; 1.4%). Mean PSA, PSA doubling time (PSAdt), and PSA velocity (PSAvel) values ± SD in (11)C-choline PET/CT-positive patients was 0.37 ± 0.1 ng/mL, 3.4 ± 2.1 months, and 0.05 ± 0.1 ng/mL/yr, respectively. (11)C-Choline PET/CT was false negative in 2 patients and false positive in 1 patient. Among all variables, only PSAdt and the ongoing hormonal treatment were statistically significant in the prediction of a positive (11)C-choline PET/CT at multivariate analysis. CONCLUSIONS: (11)C-Choline PET/CT could be used early after biochemical failure even if PSA values are very low, preferentially in hormonal resistant patients showing fast PSA kinetics. An early detection of the site of relapse could lead to a personalized and tailored treatment.

About 40% of all patients undergoing radical treatment for localized prostate cancer (PCa) develop biochemical relapse (BCR) during lifetime but only 10-20% of them will show clinically detectable recurrences. Prostatic bed, pelvic or retroperitoneal lymph nodes (LN) and bones (especially the spine) are the sites where we must focus our attention in the early phase of PSA relapse. Time to PSA relapse, PSA kinetics, pathological Gleason score and pathological stage are the main factors related to the likelihood of local vs. distant relapse. Before an extensive diagnostic work-up in patients with BCR, is mandatory to understand if there is a therapeutic consequence or not for the patient. Current imaging techniques have some potential but many limits are yet encountered in the diagnosis of disease relapse. Transrectal ultrasound (TRUS) and Multiparametric Magnetic Resonance Imaging (MRI) have low accuracy in the detection of the recurrence. Today, Choline PET/CT may visualize the site of recurrence earlier, with better accuracy than conventional imaging, in a single step and even in the presence of low PSA level. In recent years, the new radiotracer (18)F-FACBC has been proposed as a possible alternative radiopharmaceutical to detect PCa relapse. From a clinical point of view, first clinical studies showed very promising and reproducible results with an improvement in sensitivity is about 20-25% with respect to Choline PET/CT, rendering the FACBC the possible radiotracer of the future for PCa. In conclusion, many improvements have been recently achieved in imaging techniques for PCa restaging, essentially in Nuclear Medicine and MRI, but negative results remain in many cases. Low sensitivity, costs, availability of technologies and confirmation of the results remain the major limitations in most cases.

Purpose The aims of the study were (a) to evaluate the diagnostic role, by means of positive detection rate (PDR), of 18F-choline (CH) positron emission tomography (PET)/CT in patients with prostate cancer treated with radiotherapy, with curative intent, and suspicion of relapse during follow-up, (b) to correlate the PDR with trigger prostate-specific antigen (PSA), (c) to investigate the possible influence of androgen deprivation therapy (ADT) at the time of scan on PDR and (d) to assess distribution of metastatic spread.

PURPOSE: Acute infective endocarditis is a potentially life-threatening disease. Its outcome strongly depends on systemic embolization and extracardiac infections. When present, these conditions usually lead to a more aggressive therapeutic approach. However, the diagnosis of peripheral septic embolism is very challenging. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT has proven to be accurate for the detection of inflammatory diseases and occult infections. The aim of this study was to assess the added value of (18)F-FDG PET/CT in the detection of extracardiac embolisms in the evaluation of patients with suspected valvular endocarditis (VE). METHODS: Seventy-one patients with suspected infective endocarditis, enrolled between June 2010 and December 2012, underwent (18)F-FDG PET/CT with the standard procedure on a dedicated PET/CT scanner. Extracardiac findings were subsequently evaluated with other imaging procedures. RESULTS: Of the 71 patients with suspicion of infective endocarditis, we found unexpected extracardiac findings in 17 patients (24 \%) without any clinical suspicion. Extracardiac findings were subsequently evaluated with other imaging procedures. CONCLUSION: PET/CT detected unexpected extra sites of infection in 24 \% of cases, leading to changes in therapeutic management in a very relevant percentage of patients. These findings may have important therapeutic implications.

PURPOSE: This study aimed to prospectively investigate F-FDG PET/CT role for the assessment of sarcoidosis activity and extension in comparison with thoracic high-resolution CT (HRCT) and to evaluate the potential clinical impact of PET/CT findings. Secondary aim was to investigate the changes in cardiac FDG uptake related to the specific preparation before PET/CT. METHODS: We prospectively enrolled biopsy proven sarcoidosis patients consecutively referred for F-FDG PET/CT since January 2010. PET/CT was performed after a fat meal followed by 12-hour fasting and compared with thoracic HRCT results obtained in supine position and clinical follow-up. The impact on the clinical management was recorded.Patterns of cardiac FDG uptake of the study group were compared with a historical population in which PET/CT was performed following standard preparation. RESULTS: A total of 28 patients were enrolled, and 35 PET/CT scans were reviewed. On a scan basis, PET/CT was concordant with HRCT in 16 (45.7%), detecting active disease in 10/16 and no signs of activity in 4/16. PET/CT data had a direct impact on management in 4/16.In 19 (54.3%) discordant scans, PET/CT finding was positive in 14 and negative in 5. PET/CT findings influenced the clinical management in 18/19 cases.Considering all scans, PET/CT information influenced the clinical management of 22 (63%) of 35.Our data suggest that cardiac FDG uptake may vary regardless of the preparation before PET/CT. CONCLUSIONS: F-FDG PET/CT was useful to assess sarcoidosis activity and extension and provided valuable information for the clinical management in a single-step examination. Additional data are needed to better ascertain the optimal patient preparation before image acquisition to improve sensitivity of heart lesions.

Purpose The aim of this study is to explore the feasibility of 11C-Choline PET in the assessment of the degree of inflammation in the Chlamydia muridarum genital infection model. Procedures Forty female Balb/c mice received 2.5 mg of medroxyprogesterone acetate i.m. 9 and 2 days prior to the infection: 21 mice were infected by C. muridarum into the vaginal vault, 12 mice were treated with inactivated chlamydiae, and 7 mice were SPG buffer-treated as negative controls. Three healthy control mice were not treated with progesterone. Mice in each category were randomly subdivided in two groups: (1) sacrificed at 5, 10, 15, and 20 days for histological analysis and (2) undergoing 11C-Choline PET at days 5, 10, and 20 post-infection (20 MBq of 11C-Choline, uptake time of 10 min, acquisition through a small-animal PET tomograph for 15 min). Results Infected animals showed a significantly higher standardized uptake value than both controls and animals inoculated with heat-inactivated chlamydiae in each PET scan (P

Conventional anatomical imaging with CT and MRI has limitations in the evaluation of prostate cancer. PET is a powerful imaging technique, which can be directed toward molecular targets as diverse as glucose metabolism, density of prostate-specific membrane antigen receptors, and skeletal osteoblastic activity. Although 2-deoxy-2- 18 F-FDG-PET is the mainstay of molecular imaging, FDG has limitations in typically indolent prostate cancer. Yet, there are many useful and emerging PET tracers beyond FDG, which provide added value. These include radiotracers interrogating prostate cancer via molecular mechanisms related to the biology of choline, acetate, amino acids, bombesin, and dihydrotestosterone, among others. Choline is used for cell membrane synthesis and its metabolism is upregulated in prostate cancer. 11 C-choline and 18 F-choline are in wide clinical use outside the United States, and they have proven most beneficial for detection of recurrent prostate cancer. 11 C-acetate is an indirect biomarker of fatty acid synthesis, which is also upregulated in prostate cancer. Imaging of prostate cancer with 11 C-acetate is overall similar to the choline radiotracers yet is not as widely used. Upregulation of amino acid transport in prostate cancer provides the biologic basis for amino acid–based radiotracers. Most recent progress has been made with the nonnatural alicyclic amino acid analogue radiotracer anti -1-amino-3- 18 F-fluorocyclobutane-1-carboxylic acid (FACBC or fluciclovine) also proven most useful for the detection of recurrent prostate cancer. Other emerging PET radiotracers for prostate cancer include the bombesin group directed to the gastrin-releasing peptide receptor, 16β- 18 F-fluoro-5α-dihydrotestosterone (FDHT) that binds to the androgen receptor, and those targeting the vasoactive intestinal polypeptide receptor 1 (VPAC-1) and urokinase plasminogen activator receptor (uPAR), which are also overexpressed in prostate cancer.

Because no effective cures are available for cutaneous malignant melanoma, early diagnosis and accurate staging are of the utmost importance in increasing patient survival. Fluorodeoxyglucose positron emission tomography (PET)/computed tomography is a functional imaging technique that has contributed to ameliorating surveillance of patients with melanoma. New PET probes are under evaluation, and many have been tried in in vivo imaging protocols based on the use of small animal PET and animal models of cutaneous melanoma. Those compounds are targeted to a-melanocyte-stimulating hormone receptor and to the intracellular biosynthesis of melanin, and all of them showed promising results.

To verify the potential role and feasibility of carbidopa premedication in pediatric patients undergoing ¹⁸F-DOPA (Fluorine-18 fluorodihydroxyphenylalanine) PET scanning. MATERIALS AND METHODS: For this limited study, 5 patients (M:F=3:2; mean age 4.8 years) with a positive history for neuroblastoma who had been referred to our institution for instrumental monitoring during clinical follow-up were enrolled. In all cases, two consecutive ¹⁸F-DOPA PET scans, the first without carbidopa and the second with carbidopa premedication, were scheduled: patients received 4 MBq/kg of radiotracer and a dose of 2 mg/kg of carbidopa. Dedicated VOIs were drawn on the basal ganglia, pancreas, liver, and renal cortex. These regions were semiquantitatively analyzed at both the first and at the second ¹⁸F-DOPA scan, and mean SUV(max) values were compared using the t-test. RESULTS: On a visual basis, a clear reduction in the abdominal accumulation of (18)F-DOPA was observed in all cases after carbidopa premedication. This reduction related both to the biliary structures and the excretory system, and was accompanied by a generalized increase in soft tissue uptake. The semiquantitative analysis documented an absolute increase in SUV(max) after carbidopa premedication in the basal ganglia (3.4±1.3 vs. 2.1±0.8) and liver parenchyma (2.2±0.5 vs. 1.5±0.5), whereas SUV(max) decreased in the renal cortex (1.7±0.8 vs. 3.7±1.0) and the pancreas (2.3±0.6 vs. 3.5±0.5). The changes in SUV(max) were statistically significant for the pancreas and liver parenchyma (p=0.022 and 0.045, respectively), but not for the basal ganglia and renal cortex (p=0.143 and 0.15, respectively). CONCLUSIONS: Carbidopa premedication in the pediatric population appears feasible and seems to influence ¹⁸F-DOPA distribution in the liver and pancreas in a manner similar to that reported in adults. Larger series are however needed to properly define the clinical role of carbidopa premedication in children.

PURPOSE: In recent years, (68)Ga-DOTA-peptides positron emission tomography (PET)/CT has been increasingly used to study patients with neuroendocrine tumours (NET). However, performing specialized examinations in the appropriate contest is mandatory for both medical and economic reasons. The aim of the study is to evaluate the potential usefulness of (68)Ga-DOTA-NOC PET/CT in patients with suspected NET. METHODS: Among the patients undergoing (68)Ga-DOTA-NOC PET/CT at our centre, we reviewed those studied for suspected NET based on the presence of either clinical signs/symptoms or imaging or raised biochemical markers or a combination of these conditions. PET/CT results were compared with clinical and imaging follow-up of at least 1 year or pathology. RESULTS: Overall 131 suspected NET cases were included. The most common condition considered suspicious for NET was the increase of blood markers (66), followed by inconclusive findings at conventional imaging (CI, 41), clinical signs/symptoms (10), equivocal (18)F-fluorodeoxyglucose (FDG) PET (7) or somatostatin receptor scintigraphy (SRS, 4), or a combination of the above (3). PET/CT results were true-positive in 17 cases, true-negative in 112 and false-negative in 2 (overall sensitivity 89.5 %, specificity 100 %). Interestingly, increased blood markers and clinical signs/symptoms were associated with the lowest frequency of true-positive findings (1/66 and 1/10, respectively), while CI findings were confirmed in one third of the cases (13/41). Overall, the incidence of NET in the studied population was 14.5 % (19/131). CONCLUSION: Our data confirm the good accuracy (98 %) of (68)Ga-DOTA-NOC PET/CT in NET lesion detection. However, our results also suggest that (68)Ga-DOTA-NOC PET/CT may not be routinely recommended in patients with a suspicion of NET based on the mere detection of increased blood markers or clinical symptoms. Positive CI alone or in association with clinical/biochemical findings is on the contrary associated with a higher probability of true-positive findings.

Lung cancer (LC) still represents one of the most common tumours in both women and men. PET/CT is a whole-body non-invasive imaging procedure that has been increasingly used for the assessment of LC patients. In particular, PET/CT added value to CT is mainly related to a more accurate staging of nodal and metastatic sites and to the evaluation of the response to therapy. Although the most common PET tracer for LC evaluation is 18F-FDG, new tracers have been proposed for the evaluation of lung neuroendocrine tumours (68Ga-DOTA-peptides, 18F-DOPA) and for the assessment of central nervous system metastasis (11C-methionine). This review focuses on the main clinical applications and accuracy of PET/CT for the detection of non-small cells lung cancer (NSCLC), broncho-alveolar carcinoma (BAC), small cells lung cancer (SCLC), lung neuroendocrine tumours (NET) and solitary pulmonary nodules (SPN).

PURPOSE: (18)F-Dopa positron emission tomography (PET)/CT has proved a valuable tool for the assessment of neuroendocrine tumours. So far no data are available on (18)F-dopa utilization in neuroblastoma (NB). Our aim was to evaluate the role of (18)F-dopa PET/CT in NB and compare its diagnostic value with that of (123)I-metaiodobenzylguanidine (MIBG) scintigraphy in patients affected by stage 3-4 NB. METHODS: We prospectively evaluated 28 paired (123)I-MIBG and (18)F-dopa PET/CT scans in 19 patients: 4 at the time of the NB diagnosis and 15 when NB relapse was suspected. For both imaging modalities we performed a scan-based and a lesion-based analysis and calculated sensitivity, specificity and accuracy. The standard of reference was based on clinical, imaging and histological data. RESULTS: NB localizations were confirmed in 17 of 19 patients. (18)F-Dopa PET/CT and (123)I-MIBG scintigraphy properly detected disease in 16 (94%) and 11 (65%), respectively. On scan-based analysis, (18)F-dopa PET/CT showed a sensitivity and accuracy of 95 and 96%, respectively, while (123)I-MIBG scanning showed a sensitivity and accuracy of 68 and 64%, respectively (p < 0.05). No significant difference in terms of specificity was found. In 9 of 28 paired scans (32%) PET/CT results influenced the patient management. We identified 156 NB localizations, 141 of which were correctly detected by (18)F-dopa PET/CT and 88 by MIBG. On lesion-based analysis, (18)F-dopa PET/CT showed a sensitivity and accuracy of 90% whereas (123)I-MIBG scintigraphy showed a sensitivity and accuracy of 56 and 57%, respectively (p < 0.001). No significant difference in terms of specificity was found. CONCLUSION: In our NB population (18)F-dopa PET/CT displayed higher overall accuracy than (123)I-MIBG scintigraphy. Consequently, we suggest (18)F-dopa PET/CT as a new opportunity for NB assessment.

Interstitial lung diseases include different clinical entities with variable prognoses. Idiopathic pulmonary fibrosis (IPF), the most common, presents the most severe outcome (death within 3–5 y), whereas nonspecific interstitial pneumonia (NSIP) shows a more indolent progression. Preclinical evidence of somatostatin receptor (SSTR) expression on fibroblasts in vitro and in lung fibrosis murine models, coupled with the longer survival of mice with fibrotic lungs treated with agents blocking SSTR, supports the hypothesis of imaging fibroblast activity in vivo by visualization of SSTR with 68Ga-DOTANOC PET/CT. The aim of this study was to evaluate 68Ga-DOTANOC PET/CT in patients with IPF and NSIP. Methods: Seven IPF patients and 7 NSIP patients were included in the study. 68Ga-DOTANOC PET/CT and high-resolution CT (HRCT) were performed in all cases by following a standard procedure. PET/CT results were compared with disease sites and extent on HRCT. Results: In IPF, 68Ga-DOTANOC uptake was peripheral, subpleural, and directly correlated with pathologic areas on HRCT (subpleural/reticular fibrosis, honeycombing). NSIP patients showed fainter tracer uptake, whereas corresponding HRCT showed areas of ground-glass opacity and rare fibrotic changes. Only IPF patients showed a linear correlation between maximal SUV and disease extent quantified both automatically (Q) (IPF: P = 0.002, R = 0.93) and using the visual score (Spearman ρ = 0.46, P = 0.0001). Q directly correlated with percentage carbon monoxide diffusing capacity in IPF (P = 0.03, R = 0.79) and NSIP (P = 0.05, R = 0.94), whereas maximal SUV did not present any correlation with percentage carbon monoxide diffusing capacity. Conclusion: Our preliminary data show that 68Ga-DOTANOC PET/CT demonstrates SSTR overexpression in IPF patients; this may prove interesting for the evaluation of novel treatments with somatostatin analogs.

Apart from the historical and clinical relevance of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG), various other new tracers are gaining a remarkable place in functional imaging. Their contribution to clinical decision-making is irreplaceable in several disciplines. In this brief review we aimed to describe the main non-FDG PET tracers based on their clinical relevance and application for patient care.

Sarcomas are a heterogeneous group of tumors that generally present a poor prognosis. Recently, (18)F fluorodeoxyglucose (FDG-Positron emission tomography (PET)/computed tomography (CT) was introduced in clinical practice as a possible tool to improve the accuracy of staging these malignant diseases, assess the response to therapy, and as a new prognostic factor. Despite promising results presented in the recent literature, the role of PET imaging is not yet defined in the diagnostic flow chart of sarcomas. This article will describe the results reported in the literature on the use of FDG-PET/CT for the evaluation of patients with sarcoma. A short description of other PET tracers is also added.

The in vivo evaluation of three modified polyethylene glycol (PEG)-anilinoquinazoline derivatives labeled with (124)I, (18)F, and (11)C as potential positron emission tomography (PET) bioprobes for visualizing epidermal growth factor receptor (EGFR) in cancer using small animal PET. PROCEDURES: Xenograft mice with the human glioblastoma cell lines U138MG (lacking EGFR expression) and U87MG.wtEGFR (transfected with an overexpressing human wild-type EGFR gene) were used. Static and dynamic PET imaging was conducted for all three PEGylated compounds. Tumor necrosis, microvessel density, and EGFR levels were evaluated by histopathology and enzyme-linked immunosorbent assay. RESULTS: Nineteen animal models were generated (two U138MG, three U87MG, 14 with both U138MG and U87MG bilateral masses). In static images, a slight increase in tracer uptake was observed in tumors, but in general, there was no retention of tracer uptake over time and no difference in uptake between U138MG and U87MG masses. In addition, no significant uptake was demonstrated in dynamic scans of the (18)F-PEG tracer. No necrosis was present except in four animals. MVD was 9.6 and 48 microvessels/×400 field in the U138GM and U87GM masses, respectively (p = 0.00008). Similarly, the microvessel grades were generally higher in the U87GM group (p = 0.002). Total EGFR amount was higher in U87MG than U138MG masses (p = 0.001), but the ratio of activated (pY1068) to total EGFR did not differ (p = 0.95). CONCLUSIONS: PEGylated tracers labeled with (11)C, (124)I, and (18)F showed no significant difference in uptake between U138MG and U87MG glioblastoma xenograft mice. The tracer binding with EGFR could be influenced by activation of the tyrosine kinase portion of the receptor which was similar in U138MG and U87MG. Despite these results, these tracers should be investigated in animal models with mutant EGFR genes to determine whether aberrant receptor function plays a role in tumor uptake