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Background: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [ 123 I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [ 123 I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [ 123 I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals., Methods: We searched the PubMed database for studies performing a head-to-head comparison between [ 123 I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([ 11 C]C-HED), 18 F-18F-3,4-dihydroxyphenylalanine ([ 18 F]DOPA) [ 124 I]mIBG and Meta-[18F]fluorobenzylguanidine ([ 18 F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA)., Results: Ten studies were selected: two regarding [ 11 C]C-HED, four [ 18 F]DOPA, one [ 124 I]mIBG, and three [ 18 F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [ 18 F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies., Conclusions: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination., (© 2023. The Author(s).)

Purpose: The proPSMA trial at ten Australian centers demonstrated increased sensitivity and specificity for PSMA PET/CT compared to conventional imaging regarding metastatic status in primary high-risk prostate cancer patients. A cost-effectiveness analysis showed benefits of PSMA PET/CT over conventional imaging for the Australian setting. However, comparable data for other countries are lacking. Therefore, we aimed to verify the cost-effectiveness of PSMA PET/CT in several European countries as well as the USA., Methods: Clinical data on diagnostic accuracy were derived from the proPSMA trial. Costs for PSMA PET/CT and conventional imaging were taken from reimbursements of national health systems and individual billing information of selected centers in Belgium, Germany, Italy, the Netherlands, and the USA. For comparability, scan duration and the decision tree of the analysis were adopted from the Australian cost-effectiveness study., Results: In contrast to the Australian setting, PSMA PET/CT was primarily associated with increased costs in the studied centers in Europe and the USA. Mainly, the scan duration had an impact on the cost-effectiveness. However, costs for an accurate diagnosis using PSMA PET/CT seemed reasonably low compared to the potential consequential costs of an inaccurate diagnosis., Conclusion: We assume that the use of PSMA PET/CT is appropriate from a health economic perspective, but this will need to be verified by a prospective evaluation of patients at initial diagnosis., (© 2023. The Author(s).)

Positron emission tomography (PET) has been widely used in paediatric oncology. 2-Deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) is the most commonly used radiopharmaceutical for PET imaging. For oncological brain imaging, different amino acid PET radiopharmaceuticals have been introduced in the last years. The purpose of this document is to provide imaging specialists and clinicians guidelines for indication, acquisition, and interpretation of [ 18 F]FDG and radiolabelled amino acid PET in paediatric patients affected by brain gliomas. There is no high level of evidence for all recommendations suggested in this paper. These recommendations represent instead the consensus opinion of experienced leaders in the field. Further studies are needed to reach evidence-based recommendations for the applications of [ 18 F]FDG and radiolabelled amino acid PET in paediatric neuro-oncology. These recommendations are not intended to be a substitute for national and international legal or regulatory provisions and should be considered in the context of good practice in nuclear medicine. The present guidelines/standards were developed collaboratively by the EANM and SNMMI with the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group and the Response Assessment in Paediatric Neuro-Oncology (RAPNO) working group. They summarize also the views of the Neuroimaging and Oncology and Theranostics Committees of the EANM and reflect recommendations for which the EANM and other societies cannot be held responsible., (© 2022. The Author(s).)

These joint practice guidelines, or procedure standards, were developed collaboratively by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the working group for Response Assessment in Neurooncology with PET (PET-RANO). Brain PET imaging is being increasingly used to supplement MRI in the clinical management of glioma. The aim of these standards/guidelines is to assist nuclear medicine practitioners in recommending, performing, interpreting and reporting the results of brain PET imaging in patients with glioma to achieve a high-quality imaging standard for PET using FDG and the radiolabelled amino acids MET, FET and FDOPA. This will help promote the appropriate use of PET imaging and contribute to evidence-based medicine that may improve the diagnostic impact of this technique in neurooncological practice. The present document replaces a former version of the guidelines published in 2006 (Vander Borght et al. Eur J Nucl Med Mol Imaging. 33:1374-80, 2006), and supplements a recent evidence-based recommendation by the PET-RANO working group and EANO on the clinical use of PET imaging in patients with glioma (Albert et al. Neuro Oncol. 18:1199-208, 2016). The information provided should be taken in the context of local conditions and regulations.

Purpose: We present the results of an investigation of the role of FDG PET in response evaluation of bulky masses in paediatric patients with Hodgkin's lymphoma (HL) enrolled in the Italian AIEOP-LH2004 trial., Methods: We analysed data derived from 703 patients (388 male, 315 female; mean age 13 years) with HL and enrolled in 41 different Italian centres from March 2004 to September 2012, all treated with the AIEOP-LH2004 protocol. The cohort comprised 309 patients with a bulky mass, of whom 263 were evaluated with FDG PET at baseline and after four cycles of chemotherapy. Responses were determined according to combined functional and morphological criteria. Patients were followed up for a mean period of 43 months and for each child we calculated time-to-progression (TTP) and relapse rates considering clinical monitoring, and instrumental and histological data as the reference standard. Statistical analyses were performed for FDG PET and morphological responses with respect to TTP. Multivariate analysis was used to define independent predictive factors., Results: Overall, response evaluation revealed 238 PET-negative patients (90.5%) and 25 PET-positive patients (9.5%), with a significant difference in TTP between these groups (mean TTP: 32.67 months for negative scans, 23.8 months for positive scans; p < 0.0001, log-rank test). In the same cohort, computed tomography showed a complete response (CR) in 85 patients (32.3%), progressive disease (PD) in 6 patients (2.3%), and a partial response (PR) in 165 patients (62.7%), with a significant difference in TTP between patients with CR and patients with PD (31.1 months and 7.9 months, respectively; p < 0.001, log-rank test). Similarly, there was a significant difference in relapse rates between PET-positive and PET-negative patients (p = 0000). In patients with PR, there was also a significant difference in TTP between PET-positive and PET-negative patients (24.6 months and 34.9 months, respectively; p < 0.0001). In the multivariate analysis with correction for multiple testing, only the PET result was an independent predictive factor in both the entire cohort of patients and the subgroup showing PR on CT (p < 0.01)., Conclusion: After four cycles of chemotherapy, FDG PET response assessment in paediatric HL patients with a bulky mass is a good predictor of TTP and disease outcome. Moreover, in patients with a PR on CT, PET was able to differentiate those with a longer TTP. In paediatric HL patients with a bulky mass and in patients with a PR on CT, response on FDG PET was an independent predictive factor.

This paper follows the immunotherapy symposium held during the European Association of Nuclear Medicine (EANM) 2017 Annual Congress. The biological basis of the immune checkpoint inhibitors and the drugs most frequently used for the treatment of solid tumours are reviewed. The issues of pseudoprogression (frequency, timeline), hyperprogression and immune-related side effects are discussed, as well as their implications for patient management. A review of the recent literature on the use of FDG PET for assessment of immunotherapy is presented, and recommendations are provided for assessing tumour response and reporting immune-related side effects with FDG PET based on published data and experts' experience. Representative clinical cases are also discussed.

Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on 123 I-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with 18 F-FDG, 18 F-DOPA and 68 Ga-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.

The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types. However, not all patients respond to immune checkpoint inhibitors, hence, specific biomarkers are necessary to guide and monitor therapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials, but, to date, no consensus has been reached on whether PD-L1 expression is an ideal marker for response and patient selection; approximately 20-25% of patients will respond to immunotherapy with checkpoint inhibitors despite a negative PD-L1 staining. On the other hand, major issues concern the evaluation of objective response in patients treated with immunotherapy. Pure morphological criteria as commonly used in solid tumors (i.e. RECIST) are not sufficient because change in size is not an early and reliable marker of tumor response to biological therapies. Thus, the scientific community has required a continuous adaptation of immune-related response criteria (irRC) to overcome the problem. In this context, metabolic information and antibody-based imaging with positron emission tomography (PET) have been investigated, providing a powerful approach for an optimal stratification of patients at staging and during the evaluation of the response to therapy. In the present review we provide an overview on the clinical characteristics of patient selection when using imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors.

Purpose: We evaluated the relationship between 11 C-methionine PET ( 11 C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery., Methods: A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative 11 C-METH PET were analysed. Semiquantitative evaluation of the 11 C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV). Imaging findings were correlated with disease outcome in terms of progression-free survival (PFS), and compared with other clinical biological data, including IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation. The patients were monitored for a mean period of 16.7 months (median 13 months)., Results: In all patients, the tumour was identified on 11 C-METH PET. Significant differences in SUVmax, SUVratio and MTV were observed in relation to tumour grade (p < 0.001). IDH1 mutation was found in 49 patients, 1p/19q codeletion in 58 patients and MGMT promoter methylation in 74 patients. SUVmax and SUVratio were significantly inversely correlated with the presence of IDH1 mutation (p < 0.001). Using the 2016 WHO classification, SUVmax and SUVratio were significantly higher in patients with primary glioblastoma (IDH1-negative) than in those with other diffuse gliomas (p < 0.001). Relapse or progression was documented in 48 patients (median PFS 8.7 months). Cox regression analysis showed that SUVmax and SUVratio, tumour grade, tumour type on 2016 WHO classification, IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation were significantly associated with PFS. None of these factors was found to be an independent prognostic factor in multivariate analysis., Conclusion: 11 C-METH PET parameters are significantly correlated with histological grade and IDH1 mutation status in patients with glioma. Grade, pathological classification, molecular biomarkers, SUVmax and SUVratio were prognostic factors for PFS in this cohort of patients. The trial was registered with ClinicalTrials.gov (registration: NCT02518061).

Purpose: Eliciting antitumor T-cell response by targeting the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a novel therapeutic strategy in non-small cell lung cancer (NSCLC). The identification of predictors for sensitivity or resistance to these agents is, therefore, needed. Herein, we investigate the correlation of metabolic information on FDG-PET with tissue expression of immune-checkpoints and other markers of tumor-related immunity in resected NSCLC patients., Materials and Methods: All patients referred to our institution for upfront surgical resection of NSCLC, who were investigated with FDG-PET prior to surgery, were consecutively included in the study. From January 2010 to May 2014, 55 patients (stage IA-IIIB; M:F = 42:13; mean age 68.9 years) were investigated. Sampled surgical tumor specimens were analyzed by immunohistochemistry (IHC) for CD68-TAMs (tumor-associated macrophages), CD8-TILs (tumor infiltrating lymphocytes), PD-1-TILs, and PD-L1 tumor expression. Immunoreactivity was evaluated, and scores were compared with imaging findings. FDG-PET images were analyzed to define semi-quantitative parameters: SUVmax and SUVmean. Metabolic information on FDG-PET was correlated with tissue markers expression and disease-free survival (DFS) considering a median follow-up of 16.2 months., Results: Thirty-six adenocarcinomas (ADC), 18 squamous cell carcinomas (SCC), and one sarcomatoid carcinoma were analyzed. All tumors resulted positive at FDG-PET: median SUVmax 11.3 (range: 2.3-32.5) and SUVmean 6.4 (range: 1.5-13) both resulted significantly higher in SCC compared to other NSCLC histotypes (p = 0.007 and 0.048, respectively). IHC demonstrated a median immunoreactive surface covered by CD68-TAMs of 5.41 % (range: 0.84-14.01 %), CD8-TILs of 2.9 % (range: 0.11-11.92 %), PD-1 of 0.65 % (range: 0.02-5.87 %), and PD-L1 of 0.7 % (range: 0.03-10.29 %). We found a statistically significant correlation between SUVmax and SUVmean with the expression of CD8 TILs (rho = 0.31; p = 0.027) and PD-1 (rho = 0.33; p = 0.017 and rho = 0.36; p = 0.009, respectively). The other tissue markers correlated as follows: CD8 TILs and PD-1 (rho = 0.45; p = 0.001), CD8 TILs and PD-L1 (rho = 0.41; p = 0.003), CD68-TAMs and PD-L1 (rho = 0.30; p = 0.027), PD-1 and PD-L1 (rho = 0.26; p = 0.059). With respect to patients' outcome, SUVmax, SUVmean, and disease stage showed a statistically significant correlation with DFS (p = 0.002, 0.004, and <0.001, respectively)., Conclusions: The present study shows a direct association between metabolic parameters on FDG-PET and the expression of tumor-related immunity markers, suggesting a potential role for FDG-PET to characterize the tumor microenvironment and select NSCLC patients candidate to checkpoint inhibitors.

Purpose: To assess the diagnostic performance of (18)F-DOPA PET/CT and fused (18)F-DOPA PET/MRI in detecting striatal involvement in children with gliomas., Methods: This retrospective study included 28 paediatric patients referred to our institution for the presence of primary, residual or recurrent glioma (12 boys, 16 girls; mean age 10.7 years) and investigated with (18)F-DOPA PET/CT and brain MRI. Fused (18)F-DOPA PET/MR images were obtained and compared with PET/CT and MRI images. Accuracy, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for striatal involvement were calculated for each diagnostic tool. Univariate and multivariate logistic analyses were applied to evaluate the associations between (18)F-DOPA PET/CT and fused (18)F-DOPA PET/MRI diagnostic results and tumour uptake outside the striatum, grade, dimension and site of striatal involvement (ventral and/or dorsal)., Results: Accuracy, sensitivity, specificity, PPV, and NPV were 100 % for MRI, 93 %, 89 %, 100 %, 100 % and 82 % for (18)F-DOPA PET/MRI, and 75 %, 74 %, 78 %, 88 % and 58 % for (18)F-DOPA PET/CT, respectively. (18)F-DOPA PET/MRI showed a trend towards higher accuracy compared with (18)F-DOPA PET/CT (p = 0.06). MRI showed significantly higher accuracy compared with (18)F-DOPA PET/CT (p = 0.01), but there was no significant difference between MRI and (18)F-DOPA PET/MRI. Both univariate and multivariate logistic analyses showed a significant association (OR 8.0 and 7.7, respectively) between the tumour-to-normal striatal uptake (T/S) ratio and the diagnostic ability of (18)F-DOPA PET/CT (p = 0.03). A strong significant association was also found between involvement of the dorsal striatum and the (18)F-DOPA PET/CT results (p = 0.001), with a perfect prediction of involvement of the dorsal striatum by (18)F-DOPA PET/MRI., Conclusion: Physiological striatal (18)F-DOPA uptake does not appear to be a main limitation in the evaluation of basal ganglia involvement.(18)F-DOPA PET/CT correctly detected involvement of the dorsal striatum in lesions with a T/S ratio >1, but appeared to be less suitable for evaluation of the ventral striatum. The use of fused (18)F-DOPA PET/MRI further improves the accuracy and is essential for evaluation of the ventral striatum.

Purpose: In recent decades, the use of radiopharmaceuticals in the assessment of hepatocellular carcinoma (HCC) has become established, and new findings indicate that radiolabelled choline has considerable potential in this setting. Therefore, in this study we aimed to assess the diagnostic role of (11)C-choline positron emission tomography (PET)/CT, compared with conventional imaging with CT/MRI, in patients with HCC., Methods: The study population comprised 45 patients (male to female ratio = 37:8, median age 70.5 years) referred to our institution owing to HCC: 27 at initial diagnosis and 18 for restaging after recurrence. In all cases we performed whole-body (11)C-choline PET/CT and compared its findings with contrast-enhanced CT (n = 35) or MRI (n = 29) or both (n = 15) for a total of 50 paired scans. The reference standard was either histological proof (21 patients) or a multidisciplinary consensus. Diagnostic accuracy was then determined in a scan-based (SBA) and a lesion-based analysis (LBA)., Results: On SBA the sensitivity and specificity for PET were 88 and 90 %, respectively, whereas for CT/MRI they were 90 and 73 %, respectively (p > 0.05). On LBA the overall sensitivity and specificity were 78 and 86 %, respectively, for PET vs 65 and 55 % for CT/MRI. Overall we investigated 168 disease sites, of which 100 were in the liver and 68 were extrahepatic. When considering only liver lesions, (11)C-choline PET and CT/MRI showed an accuracy of 66 and 85 %, respectively, while for extrahepatic lesions PET showed an accuracy of 99 %, while the accuracy of CT/MRI was 32 %. In both cases, there was a statistically significant difference in accuracy between the two modalities (p < 0.01). Combination of the PET results with those of CT/MRI resulted in the highest diagnostic accuracy in both analyses, at 92 % for SBA and 96 % for LBA. In 11 patients (24 %) the PET findings modified the therapeutic strategy, the modification proving appropriate in 10 of them., Conclusion: (11)C-Choline PET showed good accuracy in investigating patients with HCC and prompted a change in treatment planning in almost one fourth of patients. The main strength of (11)C-choline PET/CT resides in its ability to detect extrahepatic HCC localizations, but the combination with conventional imaging modalities allowed for the highest diagnostic accuracy.

Purpose: Quantitative analyses on FDG PET for response assessment are increasingly used in clinical studies, particularly with respect to tumours in which radiological assessment is challenging and complete metabolic response is rarely achieved after treatment. A typical example is malignant pleural mesothelioma (MPM), an aggressive tumour originating from mesothelial cells of the pleura. We present our results concerning the use of semiquantitative and quantitative parameters, evaluated at the baseline and interim PET examinations, for the prediction of treatment response and disease outcome in patients with MPM., Methods: We retrospectively analysed data derived from 131 patients (88 men, 43 women; mean age 66 years) with MPM who were referred to our institution for treatment between May 2004 and July 2013. Patients were investigated using FDG PET at baseline and after two cycles of pemetrexed-based chemotherapy. Responses were determined using modified RECIST criteria based on the best CT response after treatment. Disease control rate, progression-free survival (PFS) and overall survival (OS) were calculated for the whole population and were correlated with semiquantitative and quantitative parameters evaluated at the baseline and interim PET examinations; these included SUVmax, total lesion glycolysis (TLG), percentage change in SUVmax (ΔSUVmax) and percentage change in TLG (ΔTLG)., Results: Disease control was achieved in 84.7 % of the patients, and median PFS and OS for the entire cohort were 7.2 and 14.3 months, respectively. The log-rank test showed a statistically significant difference in PFS between patients with radiological progression and those with partial response (PR) or stable disease (SD) (1.8 vs. 8.6 months, p < 0.001). Baseline SUVmax and TLG showed a statistically significant correlation with PFS and OS (p < 0.001). In the entire population, both ΔSUVmax and ΔTLG were correlated with disease control based on best CT response (p < 0.001). ΔSUVmax was significantly correlated with PFS in the entire population (p = 0.02) and with both PFS and OS in patients not undergoing talc pleurodesis (n = 65; p < 0.01 for PFS, p = 0.03 for OS), and in patients without pleurodesis presenting a SD and/or PR at CT after two cycles., Conclusion: These results confirm the role of FDG PET in the assessment of disease prognosis and treatment efficacy in MPM patients receiving first-line pemetrexed-based chemotherapy. In particular, metabolic response evaluated using ΔSUVmax can be used to predict outcome in MPM patients not undergoing talc pleurodesis who achieve SD and/or PR at the interim CT evaluation.

We are getting used to referring to instrumentally detectable biological features in medical language as "imaging biomarkers". These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context.

Purpose: The first aim of the review (aim 1) was to obtain the diagnostic performance values of (18)F-FDG PET for the detection and staging of liver metastases in patients with colorectal cancer (CRC), the second aim (aim 2) was to compare PET and conventional imaging modalities, and the third aim (aim 3) was to evaluate the impact of PET on patient management. The incidence of extrahepatic disease (EHD) detected by PET is also reviewed., Methods: A comprehensive search was performed on PubMed/MEDLINE for studies evaluating PET and PET/CT in CRC patients with liver metastases up to June 2014. For inclusion PET had to have been performed prior to surgery, there had to be at least 18 patients in the study, and the reported data had to allow calculation of 2 × 2 contingency tables (for aim 1). A total of 18 studies were eligible for at least one of the three intended subanalyses including a total of 1,059 patients. Pooled sensitivity, specificity and accuracy and the corresponding 95 % confidence intervals were derived from the contingency tables on a patient basis (patient-based analysis, PBA) and a lesion basis (lesion-based analysis, LBA) for eight studies., Results: Pooled sensitivity and specificity of PET on PBA were both 93 %. Corresponding values for LBA were 60 % and 79 %, respectively. Areas under the summary ROC were 0.97 for PBA and 0.67 for LBA. Regarding aim 2, PET had a slightly lower sensitivity than MRI and CT on PBA (93 %, 100 % and 98 %, respectively) and LBA (66 %, 89 % and 79 %, respectively) but appeared to be more specific than MRI and CT (86 %, 81 % and 67 %, respectively). PET findings resulted in changes in the management of a mean of 24 % of patients. The mean incidence of PET-based EHD was 32 %., Conclusion: This meta-analysis suggests that FDG PET/CT is highly accurate for the detection of liver metastases on a patient basis but less accurate on a lesion basis. Compared to MRI, PET is less sensitive but more specific and affects the management of about one-quarter of patients.

Purpose: The aim of this study was to investigate the relationship between (123)I-metaiodobenzylguanidine (MIBG) scan semi-quantification and a new (18)F-DOPA positron emission tomography (PET)/CT score in patients with suspected or documented neuroblastoma (NB) relapse and to assess the association between these two parameters and progression-free survival (PFS)/overall survival (OS)., Methods: We analysed 24 NB patients who had undergone (123)I-MIBG and (18)F-DOPA PET/CT scans at the time of suspected relapse, after applying a proper scoring system for each scan. In time-to-event analyses, the score distributions were regarded as continuous and were categorized in tertiles and medians. We used Kaplan-Meier curves and Cox proportional hazard models for PFS and OS in order to estimate the independent prognostic impact of (123)I-MIBG and (18)F-DOPA PET/CT scans., Results: The (123)I-MIBG and (18)F-DOPA scores were highly and positively correlated (Spearman's rho = 0.8, p < 0.001). Over a median follow-up of 14 months (range 6-82), 12 cases of disease progression and 6 deaths occurred. Multivariate Cox models showed a higher risk of disease progression [hazard ratio (HR) 17.0, 95% confidence interval (CI) 2.7-109] in NB patients with (123)I-MIBG score > 3 (3rd tertile) and an even higher risk (HR:37.2, 95% CI 2.4-574) in those with (18)F-DOPA whole-body metabolic burden (WBMB) >7.5 (median), after adjustment for all main clinical/pathological factors considered. Kaplan-Meier analyses showed a significant association with OS (log-rank p = 0.01 and p = 0.03 for (123)I-MIBG and (18)F-DOPA WBMB, respectively)., Conclusion: Our results confirm the good agreement between (18)F-DOPA PET/CT and (123)I-MIBG scan in patients affected by NB relapse. In time-to-event analyses, (123)I-MIBG scan and (18)F-DOPA PET/CT scores were independently and significantly associated with disease progression.

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.

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.

Aim: To evaluate the role of postchemotherapy FDG PET and compare it with other predictive factors in paediatric Hodgkin's disease (HD)., Materials and Methods: In this retrospective study, 98 paediatric patients with HD (enrolled in eight Italian centres) were analysed. Their mean age was 13.8 years (range 5-19 years). A PET scan was performed at the end of chemotherapy and reported as positive or negative on the basis of visual and/or semiquantitative analysis. True outcome was defined as remission or disease on the basis of combined criteria (clinical, instrumental and/or histological) with a mean follow-up period of 25 months. Statistical analyses were performed for the postchemotherapy PET results and other potential predictive factors (age cut-off, stage, presence of bulky masses and therapeutic group) with respect to patient outcome and progression-free survival (PFS)., Results: Overall the patients had a mean PFS of 23.5 months (range 4-46 months): 87 achieved remission (88.8%) and 11 showed disease. Of the 98 patients, 17 were positive on postchemotherapy PET . Seven patients (41%) showed disease during follow-up, and relapse occurred in only four out of the 81 patients who were negative on PET (p = 0.0001). Kaplan-Meier analysis demonstrated significant correlations between PFS and the postchemotherapy PET result (p = 0.0001) and a cut-off age at diagnosis of 13.3 years (p = 0.0337), whereas disease stage (p = 0.7404), therapeutic group (p = 0.5240) and presence of bulky masses (p = 0.2208) were not significantly correlated with PFS. Multivariate analysis confirmed a statistically significant correlation with PFS only for the postchemotherapy PET findings (p = 0.0009)., Conclusion: In paediatric HD, age at diagnosis and postchemotherapy PET results are the main predictors of patient outcome and PFS, with FDG PET being the only independent predictive factor for PFS.

The technological advances in imaging and production of radiopharmaceuticals are driving an innovative way of evaluating the targets for antineoplastic therapies. Besides the use of imaging to better delineate the volume of external beam radiation therapy in oncology, modern imaging techniques are able to identify targets for highly specific medical therapies, using chemotherapeutic drugs and antiangiogenesis molecules. Moreover, radionuclide imaging is able to select targets for radionuclide therapy and to give the way to in vivo dose calculation to target tissues and to critical organs. This contribution reports the main studies published on matched pairs dosimetry with (124)I/(131)I- and (86)Y/(90)Y-labelled radiopharmaceuticals, with an emphasis on metaiodobenzylguanidine (MIBG) and monoclonal antibodies.