Introduction Recent study results of our group demonstrated that [¹⁸F]PSMA-1007 (PSMA) PET/CT outperforms PSA response in predicting overall survival in metastatic castration-resistant prostate cancer (mCRPC) patients. However, its health economic implications for guiding treatment decisions remained unclear. This post-hoc analysis explores the potential impact of PSMA PET/CT on treatment decisions and patient-level costs, highlighting its relevance for future health economic evaluations. Methods Time from therapy initiation to therapy discontinuation and the reasons for discontinuation were studied. A swimmer plot visualised individual patient timelines and censored events. Hospital-perspective cost estimates were determined per patient. Results Among 60 patients, 53 discontinued therapy: 28 due to disease progression, 7 due to toxicity, and 18 after completing chemotherapy cycles. Seven patients remained on-treatment at the time of analysis. Costs varied by treatment duration and medication: monthly hospital costs were €1,826 for abiraterone, €3,652 for enzalutamide and €3,190 for chemotherapy. The cost of PSMA PET/CT was estimated at €1,286 and requires contextual evaluation within rapidly changing treatment pathways. Discussion PSMA PET/CT helps inform treatment decisions, but its cost is considerable relative to the cost of conventional therapy. Whether the use of PSMA PET/CT translates into avoidance of ineffective therapy or in therapy-related cost savings should be studied in formal cost-effectiveness analysis. Cost savings are less evident where conventional treatment costs are low compared with novel (but costly) targeted therapy options. Standardised imaging protocols, multicentre data and population registries are essential to strengthen the evidence base and enable future health economic evaluation.

Objective: Post-treatment surveillance after locally treated colorectal liver metastases involves CEA measurement and contrast-enhanced CT (CECT) scans. However, reactive tissue around ablated lesions can appear similar to viable tumor tissue on CECT, complicating the detection of local tumor progression (LTP). Therefore, a new imaging protocol was initiated, which incorporates [¹⁸F]FDG-PET/CT to complement CECT. This study evaluated the diagnostic accuracy of [¹⁸F]FDG-PET/CECT for early detection of disease progression after resection or thermal ablation, compared to CECT alone. Materials and methods: The study analyzed a prospective cohort of patients undergoing thermal ablation or resection, who received CECT and [¹⁸F]FDG-PET/CT scans 3–5 months post-treatment. Disease progression was confirmed by histology, consensus during a multidisciplinary team meeting or after extended follow-up. Diagnostic accuracy of [¹⁸F]FDG-PET/CECT was compared to standard practice (CEA serum levels and CECT). Results: The final analysis included 64 patients with 154 lesions. 37 patients underwent ablation, 14 patients underwent resection, and 13 patients underwent combination therapy, resulting in 93 (60%) lesions being treated with thermal ablation and 61 (40%) lesions with resection. Disease progression was found in 66% of patients, with LTP detected in 25% of treated lesions. Compared to CECT, [¹⁸F]FDG-PET/CECT had a higher diagnostic accuracy for detecting local progression after thermal ablation (AUC 0.97 vs. 0.73, p = 0.001) and hepatic resection (AUC 0.96 vs. 0.69, p = 0.03), and for detection of extrahepatic disease (AUC 0.91 vs. 0.79, p = 0.03). CEA serum levels had low diagnostic accuracy for detecting disease progression (AUC 0.60). Conclusion: [¹⁸F]FDG-PET/CECT improves diagnostic accuracy in the early follow-up of patients with locally treated colorectal liver metastases. Key Points: Question : Interpreting CECT scans after local treatment of colorectal liver metastases can be challenging because reactive tissue around treated lesions can appear similar to viable tumor tissue. Findings : [¹⁸F]FDG-PET/CECT improves the diagnostic accuracy of detecting local tumor progression after thermal ablation and resection of colorectal liver metastases. Clinical relevance : [¹⁸F]FDG-PET/CECT should be considered during follow-up after local treatment of colorectal liver metastases to identify and treat local tumor progression earlier.

INTRODUCTION: Treatment with bevacizumab achieves both tumour stabilisation or regression and preservation or improvement of hearing. However, the efficacy of bevacizumab varies between patients and within patients. Side effects due to bevacizumab treatment are also common. It would be of value to predict therapeutic response prior to initiating therapy to prevent unnecessary exposure in patients unlikely to benefit. METHODS AND ANALYSIS: We aim to recruit 25 patients with NF2-related schwannomatosis (NF2) with bilateral vestibular schwannomas. Patients will receive an intravenous injection of 37 MBq [89Zr]bevacizumab followed by positron emission tomography (PET)/CT imaging 4 days later. After clinical evaluation at baseline, patients undergo bevacizumab treatment and are followed up at 3 and 6 months. The primary objective is to examine associations between pretreatment [89Zr]bevacizumab uptake on PET/CT and changes in multiple hearing outcomes and radiological characteristics of the target tumour following treatment. Secondary outcome measures include vestibular functioning, patient reported outcome measures, cranial nerve functionality, peripheral neurology, non-target schwannoma response and renal function. Given the explorative nature of the study, associations between PET-derived metrics and clinical and radiological outcomes will be examined without formal hypothesis testing, using generalised estimating equations to account for within-patient correlation. Pairwise associations will be summarised in an association matrix with multiplicity addressed using an all-resolutions inference approach, and findings will be considered hypothesis generating. ETHICS AND DISSEMINATION: This study was submitted via the Clinical Trials Information System reviewed and approved by the Medical Research Ethics Committee Leiden-The Hague-Delft Delft. The study findings will be disseminated through publication in peer-reviewed scientific journals and by presentation at national and international conferences. TRIAL REGISTRATION NUMBER: The trial is registered at ClinicalTrials.gov Protocol Registration and Results System under the registration ID: NCT05685836.

Purpose: Radiolabelled fibroblast activation protein inhibitors (FAPI) are promising molecular imaging tracers for the diagnosis and staging of pancreatobiliary cancer. To enable treatment response assessment with [⁶⁸Ga]Ga-FAPI-46, the day-to-day variability of its uptake must be defined. This study aimed to determine the repeatability of semi-quantitative [⁶⁸Ga]Ga-FAPI-46 PET/CT measurements in pancreatobiliary cancers. Methods: Patients with pathologically confirmed pancreatobiliary cancer (pancreatic ductal adenocarcinoma (PDAC) or cholangiocarcinoma (CCA)) were included. Patients underwent two [⁶⁸Ga]Ga-FAPI-46 PET/CT scans, within 7 days, without any treatment before or between scans. Static long axial field-of-view (LAFOV) PET/CT scans were performed 60 min post-injection of [⁶⁸Ga]Ga-FAPI-46 (EARL2-compliant reconstruction). Suspected malignant lesions were semi-automatically delineated (local background-adjusted 50% isocontour of the peak standardised uptake value (SUV)) and semi-quantitative measurements were extracted (SUV_mean, SUV_peak and SUV_max). Tumour-to-background ratios (TBR) were also calculated. Repeatability was assessed using the repeatability coefficient (RC) and the intraclass correlation coefficient (ICC). Results: Twelve patients were included (seven PDAC, three perihilar CCA and two intrahepatic CCA). The median injected dose was 216 MBq (interquartile range (IQR) 167–266 MBq) and the median uptake time was 60 min (range 60–68). In total, 70 FAPI-positive lesions were delineated. The RCs of SUV_mean, SUV_peak and SUV_max were 23.7%, 23.9% and 29.8%, respectively. For the blood pool adjusted TBR_mean, TBR_peak and TBR_max, the RC’s were 21.6%, 20.8% and 28.0%, respectively. All ICCs were above 0.98. Conclusion: Semi-quantitative measurements of [⁶⁸Ga]Ga-FAPI-46 PET/CT have an excellent repeatability and can potentially be used in future studies to assess treatment response in pancreatobiliary cancers.

Background Accurate quantification of iodine uptake is essential for performing pre-treatment dosimetry of ¹³¹I therapy after redifferentiation of radioiodine-refractory thyroid cancer. Standardized procedures for ¹²⁴I PET/CT-based dosimetry are currently lacking. We aim to evaluate the relation between ¹⁸F and ¹²⁴I imaging for two different PET/CT scanners, the effect of bias correction on recovery across scanners and investigate the impact of clinically-encountered background (BG)-to-lesion ratios on recovery correction. Methods Cylindrical and NEMA body phantoms were scanned following vendor-recommended ¹²⁴I acquisition using clinically representative activity concentrations (5.6–5.7 kBq/mL in cylindrical phantom, 45.1–59.2 kBq/mL in NEMA spheres) and BG-to-sphere ratios (∼1:125 to 1:infinity) using two digital PET/CT scanners (Philips Vereos and GE Healthcare Omni). Additionally, BG-to-sphere ratio ∼1:10 was acquired to compare ¹²⁴I to the EARL ¹⁸F standards 1 (EARL1). Calibration accuracy and recovery coefficients (RC_max, RC_mean) were compared between scanners with and without bias correction. Results ¹²⁴I recovery was ∼20% higher for the Omni compared to the Vereos, showing calibration accuracies of 1.12–1.15 vs. 0.94, and RC_mean reaching 0.86 vs. 0.69. After bias correction, RC_mean was comparable between scanners ('1%) but below the lower limits of EARL1. A single fit for recovery correction (R² = 0.97) was obtained for different BG-to-sphere ratios for both scanners as RC_mean was comparable (p ' 0.4). Conclusion Vendor-recommended ¹²⁴I acquisition and reconstruction leads to differences in quantification but can be compensated using a bias correction. Recovery correction is minimally affected by different BG-to-lesion ratios, suggesting that one RC curve is sufficient, simplifying ¹²⁴I calibration procedures in studies requiring ¹²⁴I quantification.

Introduction: The ESMO and ECIO-ESOI consensus guidelines vary in their recommendations regarding the use of ¹⁸F-Fluorodeoxyglucose ([¹⁸F]FDG) PET/CT in the follow-up after thermal ablation in patients with colorectal liver metastases. This is partly because studies providing data on long-term benefits of [¹⁸F]FDG PET/CT are lacking. Therefore, a simulation model was developed to examine how follow-up with [¹⁸F]FDG PET/CT impacts treatment planning, health and cost outcomes. Methods: For an illustrative Dutch cohort, lifetime health and cost outcomes were simulated to assess the cost-effectiveness of performing a single additional [¹⁸F]FDG PET/CT. Patients followed a standard surveillance schedule consisting of three-monthly serum CEA and contrast-enhanced CT, plus [¹⁸F]FDG PET/CT 3–4 months after thermal ablation. Therapy could be repeated downstream the care pathway. Quality-of-life and survival estimates were based on disease stage and age. Costs were determined from a healthcare perspective incorporating costs related to diagnostics and treatments. The Consolidated Health Economic Evaluation Reporting Standards were followed. Results: Health benefits of additional [¹⁸F]FDG PET/CT were negligible, incremental QALYs < 0.001, whereas costs increased by €1,277, mainly due to the additional imaging. This lack of health benefits can be explained by the small subset of simulated patients (<5 %) in whom [¹⁸F]FDG PET/CT affected treatment planning. Discussion: Additional [¹⁸F]FDG PET/CT 3–4 months after thermal ablation is unlikely to be cost-effective. More research is needed to determine if using [¹⁸F]FDG PET/CT in subgroups of patients, or at alternative time points, is cost-effective. This requires collecting more (extensive) follow-up data across multiple centres to reflect heterogeneity between hospitals’ clinical practices.

Purpose: This study aims to systematically review and perform a meta-analysis to compare the diagnostic performance of fibroblast activation protein inhibitors (FAPI) radiopharmaceuticals and 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) in gynaecological cancers. Methods: A comprehensive search of PubMed/MEDLINE and EMBASE was conducted and updated to October 25, 2024, to identify clinical studies evaluating FAPI and [¹⁸F]FDG PET/CT or PET/MR in patients with gynaecological cancer. Quality was assessed using the QUADAS-2 tool (Quality Assessment of Diagnostic Accuracy Studies). Per-lesion pooled estimates of sensitivity, specificity, positive predictive value, and negative predictive value were calculated with 95% confidence intervals. Results: Ten studies were included for qualitative assessment and five studies focusing on ovarian cancer were included in the meta-analysis. The detection rates of primary cervical cancer ranged from 96 to 100% for both radiopharmaceuticals. For the primary tumour in ovarian cancer, the pooled sensitivities of ⁶⁸Ga-FAPI and [¹⁸F]FDG were 95% and 92%, and the pooled specificities were 81% for both radiopharmaceuticals. Nodal metastases detection was higher with ⁶⁸Ga-FAPI compared with [¹⁸F]FDG in cervical cancer. Similarly, in ovarian cancer the estimated pooled sensitivities of ⁶⁸Ga-FAPI and [¹⁸F]FDG were 97% and 88%, and the pooled specificities were 83% and 41%, respectively. At peritoneal metastases analysis in ovarian cancer, the pooled sensitivities of ⁶⁸Ga-FAPI and [¹⁸F]FDG were 97% and 70%, and the pooled specificities were 93% and 88%, respectively. At the visual assessment of peritoneal cancer scores, such as peritoneal cancer index, ⁶⁸Ga-FAPI detected a greater tumour burden compared with [¹⁸F]FDG. A comparative analysis of the PET semiquantitative parameters was also performed. Conclusion: Despite limited literature data, radiopharmaceuticals based on FAPIs are a promising alternative to [¹⁸F]FDG for imaging gynaecological cancers, in particular for the detection of nodal metastases in cervical and ovarian cancers, as well as for detecting peritoneal metastases in ovarian cancers. Larger prospective studies are needed to confirm these results and promote the inclusion of FAPI radiopharmaceuticals in clinical practice. Clinical trial number: Not applicable.

Purpose: Nipple discharge is the third most common breast-related complaint. It is recommended to exclude malignancy in pathologic nipple discharge (PND). Mammography and ultrasound are the first-line conventional diagnostic (CD) imaging. Although magnetic resonance is often used as a complementary modality, molecular breast imaging (MBI) with Tc-99m sestamibi may be a suitable alternative. Considering the lack of information on this subject and its clinical importance, this study aimed to evaluate the role of MBI in ruling out malignancy in patients with PND and negative/indeterminate CD. Patients and Methods: Retrospective cohort single-center study including all patients with PND evaluated by CD and MBI between 2012 and 2020. Pathology was considered the gold standard. Follow-up was used when pathology was not available. Results: Of the 96 cases of PND included, 78 were benign, and 18 (20%) corresponded to breast cancer (BC). Although CD and MBI were concordant in the BIRADS classification in 81% (78/96), half of BC were detected by MBI only. BC was located directly behind the nipple in a minority of patients (11%), meaning that MBI could significantly prevent futile central ductal excision. MBI presented higher sensitivity (83% vs. 33%) and negative predictive value (96% vs. 86%) than CD alone, with similar specificity (89% vs. 92%) and positive predictive value (63% vs. 50%). The area under the curve of MBI and CD was 0,86 (P-value<0.001 [95% CI: 0.75-0.97]) and 0.63 (P-value=0.091 [95% CI: 0.47-0.79]), respectively. Conclusions: MBI showed good diagnostic accuracy for detecting BC in patients with PND with negative/indeterminate findings on CD imaging.

BACKGROUND: In patients with nonischemic cardiomyopathy and no late gadolinium enhancement (LGE) on cardiac magnetic resonance, risk prediction for the occurrence of sustained ventricular arrhythmias (VA) is challenging. Global and regional sympathetic denervation has been associated with VA in patients with ischemic cardiomyopathy. Its prognostic relevance in nonischemic cardiomyopathy is unknown. METHODS: Consecutive patients from the Leiden Nonischemic Cardiomyopathy Study who underwent programmed electrical stimulation, LGE-cardiac magnetic resonance, and 123-iodine meta-iodobenzylguanidine imaging between 2011 and 2019 were included. The presence of LGE and global and regional sympathetic denervation on 123-iodine meta-iodobenzylguanidine were evaluated, and patients were followed for the occurrence of VA. Global denervation was assessed using the heart-to-mediastinum ratio. Regional denervation was evaluated by calculating the number of denervated segments (DS), the ratio of DS, the summed defect score, and the weighted denervation size. RESULTS: Of 75 included patients (median age 63 years [25th-75th interquartile range (IQR) 54-68], 79% male, left ventricular ejection fraction 36% [IQR, 27-44], 37% inducible for VA), 35 had no LGE. During 4.5±1.6 years of mean follow-up, VA occurred in 8 of 35 (23%) patients without LGE and in 18 of 40 (45%) patients with LGE. Among patients without LGE, those with VA had greater regional sympathetic denervation (median number of DS 8 [IQR, 7-10] versus 2 [IQR, 1-5], P=0.004; median ratio of DS 0.5 [IQR, 0.5-0.7] versus 0.2 [IQR, 0.1-0.4], P=0.007; median defect score 36 [IQR, 30-41] versus 18 [IQR, 14-24], P=0.01; median weighted denervation size 47 [IQR, 38-54] versus 22 [IQR, 14-30]; P=0.01). In bivariate analysis, the number of DS (hazard ratio, 1.25 [95% CI, 1.06-1.46]; P=0.006) was associated with the occurrence of VA in patients without LGE. Denervation of ≥7 segments identified patients without LGE at risk for VA (area under the curve, 0.83; sensitivity, 88%; specificity, 89%). Among patients with LGE, the innervation state was not associated with VA during follow-up. CONCLUSIONS: In patients with nonischemic cardiomyopathy without LGE the extent of regional denervation may contribute to risk stratification for VA.

The appropriate use criteria (AUC) documents are intended to aid medical practitioners in the appropriate use of imaging technology in specific clinical scenarios based on rigorous appraisal of the available published evidence. The purpose of this document is to summarize the appropriate use of PET/CT with ¹⁸F-FDG in the initial staging of malignant disease. A multidisciplinary expert panel convened to appraise an independently performed systematic review and develop the AUC for initial staging of head and neck cancer, lung cancer, breast cancer, esophageal cancer, colorectal cancer, pancreatic cancer, melanoma, lymphoma, myeloma, and sarcoma with an appropriateness score for each clinical scenario established by using a modified Delphi process (Table 1). The full document including the methodology details, discussion of evidence, appendices, and the supplemental material can be accessed at https://snmmi.org/Web/Clinical-Practice/Appropriate-Use-Criteria/Articles/Appropriate_Use_Criteria_for_18F-FDG_PET_CT_for_Initial_Staging_of_Malignant_Disease.

Background: Prior studies show that short-term treatment using tyrosine kinase inhibitors (TKIs) can reinduce radioiodine uptake and warrant ¹³¹I therapy in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). We aim to evaluate the potential of standard-of-care TKI lenvatinib to reinduce clinically meaningful radioiodine retention. Methods: Nine RAI-R DTC patients starting lenvatinib treatment for progressive advanced or metastatic disease, were included and underwent rhTSH-stimulated ¹²⁴I dosimetric procedures at baseline, week 6 (N=7) and week 12 (N=8). At all timepoints, the fraction of patients eligible for ¹³¹I therapy with a maximal activity of 7.4 GBq was assessed. Patients were considered eligible if at least one target lesion showed an expected mean absorbed dose ≥20 Gy. In total, 23 target lesions were segmented on¹²⁴I PET/CT images and their volumes estimated using low-dose CT images. Lesion size-specific recovery correction was applied to the measured mean activity concentration at each timepoint. Tumor dosimetry was performed using a mono-exponential fit and S-values from an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms (IDAC-Dose2.1). Mean absorbed lesion dose per administered activity (LDpA), 24h-uptake and residence time in target lesions were compared between time points. Results: By our definition, none of the patients were found eligible for ¹³¹I therapy at any timepoint. Lenvatinib-induced partial response was observed in 59% and 75% of target lesions at week 6 and 12, respectively. Median LDpA was 0.08 (IQR: 0.04-0.17), 0.18 (0.08-0.36) and 0.17 (0.09-0.37) Gy/GBq for week 0, 6 and 12, respectively (p=0.08). The 24h-uptake and residence time were comparable between timepoints (p>0.22). Conclusion: Redifferentiation of RAI-R DTC to reinduce radioiodine uptake to a level that warrants ¹³¹I therapy may not be established by short-term lenvatinib treatment. Multi-targeted TKIs may not be as potent as selective TKIs in reinducing clinically meaningful radioiodine retention.