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The Food and Drug Administration and the European Medicines Agency have recently approved chimeric antigen receptor-engineered (CAR) T cells to treat several refractory/relapsed B-cell lymphomas. This comprehensive review aims to demonstrate the pivotal role that [ 18 F]-FDG PET/computed tomographic (CT) imaging can play to enhance the care of patients treated with CAR T-cell therapy. To this end, this review deciphers evidence showing the diagnostic, prognostic, predictive, and theragnostic value of [ 18 F]-FDG PET/CT-derived parameters., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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: To compare the diagnostic performance of 68 Ga-PSMA PET/TC with PRI-MUS (prostate risk identification using micro-ultrasound) in the primary diagnosis of prostate cancer (PCa)., Methods: From September till December 2018, we prospectively enrolled 25 candidates to 68 Ga-PSMA PET/TRUS (transrectal ultrasound) fusion biopsy and compared them with PRI-MUS. This included patients with persistently elevated PSA and/or PHI (prostate health index) suspicious for PCa, negative digital rectal examination, with either negative or contraindication to mpMRI, and at least one negative biopsy. The diagnostic performance of the two modalities was calculated based on pathology results., Results: Overall, 20 patients were addressed to 68 Ga-PSMA PET/TRUS fusion biopsy. Mean SUVmax and SUVratio for PCa lesions resulted significantly higher than in benign lesions (p = 0.041 and 0.011, respectively). Using optimal cut-off points, 68 Ga-PSMA PET/CT demonstrated an overall accuracy of 83% for SUVmax ≥ 5.4 and 94% for SUVratio ≥ 2.2 in the detection of clinically significant PCa (GS ≥ 7). On counterpart, PRI-MUS results were: score 3 in nine patients (45%), score 4 in ten patients (50%), and one patient with score 5. PRI-MUS score 4 and 5 demonstrated an overall accuracy of 61% in detecting clinically significant PCa., Conclusion: In this highly-selected patient population, in comparison to PRI-MUS, 68 Ga-PSMA PET/CT shows a higher diagnostic performance.

Response assessment in malignant lymphoma has progressively evolved in the last 20 years, leading to continuous adaptations to clinical requirements and technology improvements. The latest challenge in treatment evaluation is represented by immunomodulatory drugs, capable of stimulating response to cancer by unleashing the immune system of the host. Despite the consolidated consensus on the use of Deauville score and Lugano criteria for the assessment of first-line therapeutic regimens, during other lines of treatment and, particularly, during the course of immunotherapy, response parameters and clinical evidence appear less clear., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: aim is outcome of 11C-Choline-PET guided SBRT on lymph node metastases., Materials and Methods: patients with 1 - 4 lymph node metastases detected by 11C-choline-PET were treated with SBRT. Toxicity, treated metastases control and Progression Free Survival were computed., Results: twenty-six patients, 38 lymph node metastases were irradiated. No grade ≥ 2 toxicity. Median PSA-nadir after RT was 1.02 ng/mL. Post-treatment 11C-Choline-PET showed metabolic complete response in 17 metastases (44,7%), partial response in 9 metastases (38%)., Conclusion: SBRT is effective and safe for lymph node metastases. PET is important in identification of gross tumor and evaluation of the response.

Purpose: Cu-ATSM is a very promising PET radiopharmaceutical for tumor imaging of hypoxia. One of the advantages of this compound compared with other hypoxia-avid tracers is the high tumor-to-background signal offered, which guaranties facilitated tumor delineation. This study analyzes optimal semiquantitative and quantitative parameters obtained by Cu-ATSM PET/CT in the same cohort of patients with special focus on their correlation to disease outcome., Patients and Methods: A prospective recruitment of 18 consecutive patients (M:F, 13:5; mean age, 60.7 years) with locally advanced non-small cell lung cancer (n = 7) or head and neck cancer (HNC) was performed. Each participant received 105 to 500 MBq of tracer according to body size and was scanned in a 3-dimensional mode PET/CT 60 minutes after tracer injection. PET images were reconstructed and visualized on a GE Advanced 4.6 workstation for the definition of semiquantitative and quantitative parameters: SUVmax, SUVratio-to-muscle, hypoxic tumor volume (HTV), and hypoxic burden (HB = HTV × SUVmean). These data were subsequently correlated to disease outcome, expressed in terms of progression-free survival calculated on a follow-up period with a median of 14.6 months., Results: All patients showed a moderately to highly increased uptake of Cu-ATSM in tumor lesions, with a mean SUVmax of 5.2 (range, 1.9-8.3) and mean SUVratio of 4.4 (range, 1.6-6.8). In addition, a broad range of HTV and HB was defined as mean values of 99.3 cm (range, 2.5-453.7 cm) and 301 (4.2-1134), respectively. Receiver operating characteristic analysis identified as reference cutoffs with respect to disease outcome with the following values: SUVmax >2.5 (AUC, 0.57; sensitivity, 88.9%; specificity, 50%), SUVratio ≤4.4 (AUC, 0.60; sensitivity, 50; specificity, 83.3%), HTV >160.7 cm (AUC, 0.61; sensitivity, 55.6%; specificity, 75%), and HB >160.7 (AUC, 0.67; sensitivity, 58.3%; specificity, 83.3%). In our cohort, HB showed a statistically significant difference in terms of mean values on the analysis of variance test with respect to disease progression (P = 0.04). On univariate analysis, Cox regression confirmed these findings and showed a significant correlation to progression-free survival for HB (P = 0.05) and HTV (P = 0.02)., Conclusions: In our cohort, the definition of optimal semiquantitative and quantitative parameters on Cu-ATSM PET/CT seems feasible and in line with previously published data. However, when considering the prognostic role with respect to disease outcome, the more robust parameters are represented by HTV and HB.

The overexpression of somatostatin receptors on the tumor cell surface of neuroendocrine tumors (NETs) detected by multimodal functional imaging modalities such as SPECT and PET tracers constitutes a therapeutic option using targeting radiolabeled compounds. We will introduce the theranostic concept in general, explain in more detail its development in NETs, and discuss available SPECT and PET tracers regarding their potential for diagnostic imaging, visualization of target expression, and treatment tailoring. Moreover, we will discuss the currently available peptide receptor radionuclide therapy principles and compare them to previously published studies. Finally, we will discuss which new concepts will most likely influence the theranostic treatment approach in NETs in the future.

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.

Carbon-11 methionine ((11)C-Methionine) is a radio-labeled amino acid currently utilized in Positron Emission Tomography (PET) for imaging primary and metastatic brain tumors. Its clinical use relies mostly on oncologic applications, but the tracer has the potential to investigate other non-malignant conditions. So far, very limited evidence concerns the use of (11)C-Methionine in patients suffering from seizure; however, the tracer can find a proper utilization in this setting especially as a diagnostic complement to (18)F-Fluorodeoxyglucose ((18)F-FDG). Herein we report the case of a 57-year-old patient presenting with epileptic crises secondary to a brain metastasis from bladder carcinoma, who was investigated in our institution with (11)C-Methionine PET. The scan documented the disease recurrence in the left parietal lobe associated with a diffused tracer uptake in the surrounding cerebral circumvolutions, derived from the comitial status. After surgical removal of the metastatic lesion, the patient experienced a complete recovery of symptoms and no further onset of secondary seizure., (Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.)

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.

Background: The purpose of our study was to analyze the role of [(11)C]choline-positron emission tomography/computed tomography (cho-PET/CT) in the management of patients with prostate cancer referred for radiotherapy., Patients and Methods: Inclusion criteria for this retrospective study were (1) presence of prostate cancer, (2) referral for first radiotherapy course (for primary or recurrent tumor) between February 2007 and July 2010, and (3) performance of cho-PET/CT. All cho-PET/CT scans were classified according to whether they were positive in the prostate/prostate bed (T), pelvic lymph nodes (N), and distant metastases (M) or negative. Therapeutic strategy based on the cho-PET/CT evaluation was compared with the strategy that would have been proposed had cho-PET/CT imaging not been available, following international and national prostate cancer guidelines., Results: Eighty-two cho-PET/CT scans performed in 74 patients were analyzed. Cho-PET/CT was positive in 49 studies (60%): T only in 22 (45% of all positive studies); N only in 4 (8%); T in combination with N in 3 (6%); and M in combination with T or N, or both, in 16 (33%). Treatment after positive cho-PET/CT examination included radiotherapy ± androgen deprivation (29 patients), surgery ± radiotherapy (6 patients), androgen deprivation only (8 patients), and other treatment (6 patients). In 22 cases, cho-PET/CT (27%) altered the treatment approach compared with the treatment that would have been adopted in the absence of cho-PET/CT analysis., Conclusion: Cho-PET/CT is valuable in defining the extent of disease and supporting therapeutic decisions in the management of prostate cancer. The therapeutic strategy turned out to be influenced by cho-PET/CT imaging in about one third of the patients included in this study., (Copyright © 2014 Elsevier Inc. All rights reserved.)

123Iodine-metaiodobenzylguanidine (123I-MIBG) scintigraphy is currently the tracer of choice for neuroblastoma (NB). It has high diagnostic accuracy and prognostic value for the assessment of patients after chemotherapy. A positive 123I-MIBG scan is also used for the basis of targeted radionuclide therapy with 131I-MIBG. I-123 MIBG scan however has some limitations which should be taken into account. Moreover the reasons for false negative MIBG results have not been entirely elucidated. Meticulous correlation with radiological examinations and recognition of the normal distribution pattern of 123I-MIBG in children is vital to obtain optimal results. With its technical superiorities, positron emission tomography/computed tomography (PET/CT) can be successfully introduced into the diagnostic workup of NB. Different PET tracers have been offered for imaging in patients with NB, and the efficacy of this modality has been compared with that of 123I-MIBG scan. Our review aims to analyze the present role of PET/CT imaging and radiopharmaceuticals in NB.

The major application for PET imaging in clinical practice is represented by cancer imaging and (18)F-FDG is the most widely employed positron emitter compound. However, some diseases cannot be properly evaluated with this tracer and thus there is the necessity to develop more specific compounds. The last decades were a continuous factory for new radiopharmaceuticals leading to an endless list of PET tracers; however, just some of them guard diagnostic relevance in routine medical practice. This chapter describes a selected list of non-FDG PET tracers, basing on their introduction into and impact on clinical practice.

Background: The principal aim of this study was to identify the lowest nodule diameter and the SUV(max) capable of characterizing lung nodules in pediatric patients with bone sarcoma., Procedure: Eighteen consecutive bone sarcoma patients (M/F = 11:7; mean age 14 years) with suspicious lung lesions at CT were enrolled. Overall, 63 lung nodules with a mean diameter of 3.35 mm (range 1.2-39.8 mm) were investigated. (18) F-FDG PET was performed according to standard procedure using a hybrid PET/CT system and results were compared with histology and/or clinical/radiological follow-up. For each lesion, we evaluated SUV(max) , SUV(ratio) to the mediastinal blood pool and maximum nodule diameter., Results: Of the 63 nodules, 32 proved to be benign and 31 malignant. On a visual basis, (18) F-FDG PET had an accuracy of 88.9%, a sensitivity of 90.3%, a specificity of 87.5%, a PPV of 87.5%, and a NPV of 90.3%. ROC curve analysis of SUV(max) for all nodules showed a value around 1 (>1.09) to be capable of differentiating metastases from benign lesions: sensitivity and specificity were 90.3% and 93.8%, respectively (accuracy 92.1%). Similar analysis revealed a cut-off value around 1 (>0.83) for SUV(ratio) (sensitivity and specificity were 90.3% and 90.6%, respectively) and a cut-off value of ca. 6 mm (>5.8 mm) for nodule diameter (sensitivity and specificity of 90.3% and 81.3%, respectively)., Conclusions: (18) F-FDG PET/CT is an accurate modality for the metabolic characterization of lung nodules in the pediatric population with bone sarcoma, and a SUV(max) (or SUV(ratio) ) >1 is capable of discriminating malignant from benign lesions., (Copyright © 2012 Wiley Periodicals, Inc.)

Aim: 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.

This study reports on our experience with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in pediatric patients affected by Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). We studied 20 pediatric subjects (12 males, 8 females; mean age, 10 years; range, 6 months to 14 years) with malignant lymphoma (9 HD, 11 NHL) for a 4-year period of time. Overall, 45 PET scans were performed: 7 at disease presentation and 38 for evaluation of response to therapy or follow-up study. All PET results were compared with conventional imaging (CI), mainly computed tomography (CT) and/or magnetic resonance imaging (MRI), and supported by clinical follow-up and/or histologic data. In 18 of 20 patients, PET findings correctly identified the status of disease. Two (2) subjects (respectively, 1 HD and 1 NHL, both at follow-up) resulted falsely positive: 1 due to prominent thymic uptake, and the other due to nonspecific inflammation. Of 45 scans, PET findings were consistent with clinical follow-up and other CI data in 43 cases (16 true-positive and 27 true-negative results) and resulted falsely positive in the remaining 2 scans. On a lesion-by-lesion basis (overall, 153 lesions: 84 nodal and 69 extranodal), we found a concordance between CI and PET findings in 25 nodal (29.8%) and in 22 extranodal sites (32%). PET was more accurate than CI, as it identified active disease in 1 patient negative at CI and excluded relapse in 6 patients with inconclusive CI and in 2 patients with a falsely positive CI. Overall, PET sensitivity and specificity was 100% and 93% versus 94% sensitivity and 72.4% specificity for CI. This comparative study shows FDG PET to be more accurate than CI in evaluating children with lymphoma. Our data also confirms that (18)F-FDG PET may show false-positive findings.

Neuroendocrine tumours (NET) are relatively rare neoplasms affecting principally the gastroenteropancreatic tract, but with potential ubiquitary location, as the neural crest cells, origin of this group of tumours, are dispersed in various organs and tissues. After the discovery of somatostatin receptors (SSTR) over-expression in this group of neoplasms, NET management has significantly improved. This is witnessed by the development of new tracers in positron emission tomography (PET) imaging of NETs belonging to the family of radio-labelled somatostatin analogues, that significantly improved the accuracy of diagnosis and, more recently, opened the way to the innovative targeted radionuclide therapies. First introduced in clinical application in 2005, 68Ga-DOTANOC (one of the most used radio-labelled somatostatin analog for PET imaging) has revealed promising results in preliminary studies for the main clinical indications: staging NET; suspected NET of unknown primary; follow-up, restaging and, finally, for pre- and post-treatment evaluation of receptor radionuclide therapies. Due to its technically simple production, favourable biodistribution, biokinetics, dosimetry and high affinity for SSTR and thanks to the possibility of hybrid scans PET/computed tomography (CT) with better spatial resolution and localisation of the lesions, 68Ga-DOTANOC can advance as the new gold standard for imaging in neuroendocrine tumours.

The widespread use of several new non-cytotoxic drugs and the significant improvements in functional imaging highlights a number of difficulties in monitoring, interpreting and predicting treatment response in clinical practice. Certain guidelines for disease assessment after therapy are already available: the traditional Response Evaluation Criteria in Solid Tumours guidelines based on tumour size variations using conventional imaging technologies, the recent combined method developed by Choi and colleagues in gastrointestinal stromal tumour treated with tyrosine kinase inhibitors based on tumour density variations using computed tomography (CT), and the European Organization for Research and Treatment of Cancer criteria based on tumour glucose metabolism variations using fluorodeoxyglucose (FDG) positron emission tomography (PET). At the moment combined PET/CT response criteria are still not available. A number of new PET compounds other than FDG are also currently being developed to visualize specific cellular and molecular tumour pathways but their role in assessment and prediction of cancer treatment response has not yet been thoroughly investigated in a large series. However, in clinical practice many oncologists treat cancer patients with targeted therapies or chemotherapy and evaluate the response using conventional or functional imaging without appropriate and standardized guidelines. The aim of this study was to present a selection of clinical cases that illustrate the usefulness of new PET tracers and efficacy evaluation of new drugs. In the era of molecular imaging and molecular therapies, these cases highlight the urgency to develop new criteria for treatment assessment and the exigency of correctly interpreting the biological information obtained from new technologies, and introduce new concepts that require further investigation in clinical trials.