Systematic literature reviews (SLRs) are fundamental for aggregating published evidence, identifying knowledge gaps and informing health economic evaluations, especially in the field of novel diagnostics where randomised controlled trials are commonly absent [1]. The global publishing output within the field of novel diagnostics is increasing rapidly owing to increasing efforts towards precision medicine. Simultaneously, the global publishing output within the field of health economics is increasing rapidly owing to increasing efforts towards value-based healthcare and present budget constraints. The number of publications focussing on the health economic impact of diagnostics almost doubled from 86,244 in 2010 to 152,404 in 2025 (PubMed search using MeSH terms ‘Diagnostic Techniques and Procedures’ and ‘Health Care Economics and Organizations’). Consequently, the workload of performing SLRs is increasing as the number of articles that requires screening grows larger. The average time to complete an SLR is over 15 months, while the proportion of truly relevant articles for data extraction may be as low as 1% of the total search results [2]. The high workload may reduce researchers’ willingness to conduct an SLR or may lead to search strategies that are too narrow when prioritising time constraints over review quality. Moreover, it may render an SLR outdated by the time it is published.

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.

To plan optimal management in a patient with breast cancer (BC), accurate baseline staging and early detection and staging of recurrence are necessary.1-3 Representatives from the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) recently published the joint European-American guidelines on the role of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) in no special type (NST) BC, endorsed by several other imaging and clinical societies: the American College of Radiology (ACR), European Society of Surgical Oncology, European Society for Radiotherapy and Oncology (ESTRO), European Society of Breast Imaging, European Society of Radiology, and European Society of Breast Cancer Specialists (EUSOMA).1 Considering the low [18F]FDG-avidity in invasive lobular carcinoma (ILC), the EANM-SNMMI guidelines focused on NST BC. Guidelines from clinical societies such as the American National Comprehensive Cancer Network (NCCN),4 European Society for Medical Oncology (ESMO),5-7 and Advanced Breast Cancer (ABC) international consensus guidelines8 also evaluate imaging techniques, but they include all histological subtypes of BC. There is a lack of consistency in the optimal utilization of [18F]FDG-PET/CT among published guidelines. This manuscript summarizes available evidence, emphasizes the value of [18F]FDG-PET/CT for staging and restaging of patients with BC, and highlights agreements and discrepancies among international guidelines.

Purpose
Prostate-specific membrane antigen (PSMA) expression has been observed in a subset of soft tissue sarcomas, mainly in the neovascular endothelial cells. This feasibility study aimed to evaluate PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma, providing important insights for potential future exploration of PSMA-targeted radioligand therapy.

Methods
This prospective single-center study included adult patients with metastatic soft tissue sarcoma, with measurable disease (lesion diameter > 1 cm), available biopsy/resection material, ECOG/WHO performance status of 0–2 and either no prior systemic treatment, progressive disease during/after treatment, or stable disease/partial response with the last dose > 8 weeks prior. Immunohistochemical PSMA staining was performed on previously obtained biopsy or resection material. In case of high PSMA expression, a [18F]-JK-PSMA-7 PET/CT scan evaluated tracer uptake, with adequate uptake defined as SUVmax > 8.

Results
Of 25 included patients, 11 (44%) had high PSMA expression: 4/11 leiomyosarcomas, 3/4 dedifferentiated liposarcomas, 2/5 undifferentiated pleomorphic sarcomas, 1/2 myxofibrosarcomas and 1/1 malignant peripheral nerve sheath tumour. Five of 11 patients agreed to a [18F]-JK-PSMA-7 PET/CT, of which 3 had lesions that showed adequate tracer uptake (SUVmax 10.7–16.7). However, uptake across all metastatic lesions was highly heterogeneous (median SUVmax = 3.8; range 0.5–16.7), indicating that these patients are unlikely to benefit sufficiently from PSMA-targeted therapy. The study was therefore terminated prematurely.

Conclusion
PSMA expression and PSMA tracer uptake in metastatic soft tissue sarcoma were highly heterogeneous. A deeper understanding of PSMA biology and improved patient selection criteria are essential for future application of PSMA-targeted radioligand therapy in this disease.

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.

Purpose
The value of integrating clinical variables, radiomics, and tumor-derived cell-free DNA (cfDNA) for the prediction of survival and response to chemoradiation of patients with resectable esophageal adenocarcinoma is not yet known. Our aim was to investigate if radiomics and cfDNA metrics combined with clinical variables can improve personalized predictions.

Methods and Materials
A cohort of 111 patients with resectable esophageal adenocarcinoma from 2 centers treated with neoadjuvant chemoradiation therapy was used for exploratory retrospective analyses. Models combining the clinical variables of the SOURCE survival model with radiomic features and cfDNA were built using elastic net regression and internally validated using 5-fold cross-validation. Model performance for overall survival (OS) and time to progression (TTP) were evaluated with the C-index and the area under the curve for pathologic complete response.

Results
The best-performing baseline models for OS and TTP were based on the combination of SOURCE-cfDNA that reached a C-index of 0.55 and 0.59 compared with 0.44 to 0.45 with SOURCE alone. The addition of restaging positron emission tomography radiomics to SOURCE was the most promising addition for predicting OS (C-index: 0.65) and TTP (C-index: 0.60). Baseline risk stratification was achieved for OS and TTP by combining SOURCE with radiomics or cfDNA, log-rank P < .01. The best-performing combination model for the prediction of pathologic complete response reached an area under the curve of 0.61 compared with 0.47 with SOURCE variables alone.

Conclusions
The addition of radiomics and cfDNA can improve the performance of an established survival model. External validity needs to be further assessed in future studies together with the optimization of radiomic pipelines.

Objective
Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with varying survival outcomes. This study investigated whether baseline PSMA PET/CT parameters are associated with survival and treatment response.

Methods
Sixty mCRPC patients underwent [18F]PSMA-1007 PET/CT before treatment with androgen receptor-targeted agents (ARTAs) or chemotherapy. Intensity-based parameters, volumetric parameters, metastatic sites and DmaxVox (distance between the two outermost voxels) from baseline PSMA PET/CT were collected, as well as age, Gleason score and laboratory parameters. Cox regression analysis evaluated their prognostic value for overall survival (OS). Additionally, a preliminary lesion-level analysis was done (n = 241 lesions) with lesion location and twelve radiomic features selected from previous literature. Logistic regression evaluated their association with PSMA PET/CT-based lesion progression after 3–4 months of treatment.

Results
Total tumour volume (PSMA-TV) (HR = 1.41 per doubling [1.17–1.70]), total lesion uptake (TL-PSMA) (HR = 1.40 per doubling [1.16–1.69]) and DmaxVox (HR = 1.31 per 10 cm increase [1.07–1.62]) were prognostic for OS, each independent of baseline PSA level (HR = 0.82 per doubling [0.68–0.98]), haemoglobin level (HR = 0.68 per mmol/L increase [0.49–0.95]) and line of treatment. On lesion-level, location (prostate vs bone OR = 0.23 [0.06–0.83]) and SUVmean (OR = 1.72 per doubling [1.08–2.75]) were independent prognostic markers for lesion progression, morphological and texture-based radiomic features were not.

Conclusion
Baseline PSMA PET/CT scans have prognostic value in mCRPC patients and can potentially aid in treatment decision-making. DmaxVox can serve as a simpler alternative to PSMA-TV when automated segmentation software is not available. When combined with PSMA-TV, lower PSA levels indicated worse OS, which may be a marker of tumour dedifferentiation. Further research is needed to validate these models in larger patient cohorts.

Purpose
This study evaluates the semi-quantitative single-photon emission computed tomography (SPECT) parameters of prone SPECT using [99mTc]Tc-sestamibi and compares them with Molecular Breast Imaging (MBI)-derived semi-quantitative parameters for the potential use of response prediction in women with locally advanced breast cancer (LABC).

Procedures
Patients with proven LABC with a tumor ≥ 2 cm on mammography and an indication for MBI using [99mTc]Tc-sestamibi were prospectively enrolled. All patients underwent a prone SPECT/CT at 5 min (early exam) and an additional scan at 90 min (delayed exam) after injection of 600 MBq [99mTc]Tc-sestamibi to compose wash-out rates (WOR). All patients underwent MBI after early SPECT/CT. Volumes of interest of the primary tumor were drawn semi-automatically on early and delayed SPECT images. Semi-quantitative analysis included maximum and mean standardized uptake values (SUVmax, SUVmean,), functional tumor volume (FTVSPECT), total lesion mitochondrial uptake (TLMU), tumor-to-background ratios (TBRmax and TBRmean), WOR and coefficient of variation (COVSPECT). Subsequently, the FTVSPECT, TBRSPECT and COVSPECT were compared to FTVMBI, TBRMBI and COVMBI.

Results
Eighteen patients were included. Early SUVmax, and TBRmax showed significantly higher interquartile range (IQR) compared to SUVmean and TBRmean, respectively 2.22 (2.33) g/mL, 6.86 (8.69), 1.29 (1.39) g/mL and 3.99 (5.07) (median (IQR), p < 0.05). WOR showed a large IQR (62.28), indicating that there is WOR variation among the LABC patients. FTV showed no difference between MBI and early SPECT semi-quantitative parameter (p = 0.46).

Conclusions
In LABC patients it is feasible to obtain semi-quantitative parameters from prone SPECT/CT. The FTV derived from early prone SPECT/CT is comparable with MBI-based FTV. Studies with comprehensive clinical parameters are needed to establish the clinical relevance of these semi-quantitative parameters, including WOR, for response prediction before its use in clinical routine.

Objective: This single-centre retrospective study aims to determine the incidence of therapy-induced surgical benefit in patients with non-metastatic gastrointestinal stromal tumour (GIST) treated with neoadjuvant tyrosine kinase inhibitors (TKI) and evaluate whether this can be predicted by radiological response criteria. Methods: Thirty-nine non-metastatic GIST patients were treated with neoadjuvant TKI treatment, followed by curative-intended surgery, and monitored using contrast-enhanced computed tomography (CE-CT). Surgical benefit was independently assessed by two surgical oncologists and was defined by de-escalation of surgical strategy or reduced surgical complexity. Radiological response between baseline and the last preoperative scan was determined through RECIST 1.1, Choi and volumetric criteria. Results: In this patient cohort, median neoadjuvant treatment interval was 8.3 (IQR, 3.9–10.6) months. Surgical benefit was gained in 22/39 patients. When comparing radiological criteria to findings on surgical benefit, accuracy, sensitivity, and specificity for RECIST 1.1 (90 %, 100.0 % and 82 %), Choi (64 %, 24 %, and 96 %) and volumetry (95 %, 100.0 %, and 91 %) were calculated. In 30/39 patients, temporal changes in tumour size over the course of treatment was assessed. Tumour volume reduced significantly in the surgical-benefit group compared to the non-benefit group (72 % vs. 25 %, p < 0.01) within three months. 14/19 surgical-benefit patients had an initial volume reduction above 66 %, after which volume reduced slightly with a median 3.1 % (IQR, 2.1–7.8 %) reduction. Conclusion: Surgical benefit after neoadjuvant treatment was achieved in 56 % of patients and was most accurately reflected by size-based response criteria. In patients with therapy-induced surgical benefit, nearly all treatment-induced volume reductions were achieved within three months.

This study investigated whether radiomic features extracted from pretreatment [18F]FDG PET could improve the prediction of both histopathologic tumor response and survival in patients with locally advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed by surgery compared with conventional PET parameters and histopathologic features. Methods: The medical records of all consecutive patients with LACC referred between July 2010 and July 2016 were reviewed. [18F]FDG PET/CT was performed before neoadjuvant chemoradiotherapy. Radiomic features were extracted from the primary tumor volumes delineated semiautomatically on the PET images and reduced by factor analysis. A receiver-operating-characteristic analysis was performed, and conventional and radiomic features were dichotomized with Liu’s method according to pathologic response (pR) and cancer-specific death. According to the study protocol, only areas under the curve of more than 0.70 were selected for further analysis, including logistic regression analysis for response prediction and Cox regression analysis for survival prediction. Results: A total of 195 patients fulfilled the inclusion criteria. At pathologic evaluation after surgery, 131 patients (67.2%) had no or microscopic (≤3 mm) residual tumor (pR0 or pR1, respectively); 64 patients (32.8%) had macroscopic residual tumor (>3 mm, pR2). With a median follow-up of 76.0 mo (95% CI, 70.7–78.7 mo), 31.3% of patients had recurrence or progression and 20.0% died of the disease. Among conventional PET parameters, SUVmean significantly differed between pathologic responders and nonresponders. Among radiomic features, 1 shape and 3 textural features significantly differed between pathologic responders and nonresponders. Three radiomic features significantly differed between presence and absence of recurrence or progression and between presence and absence of cancer-specific death. Areas under the curve were less than 0.70 for all parameters; thus, univariate and multivariate regression analyses were not performed. Conclusion: In a large series of patients with LACC treated with neoadjuvant chemoradiotherapy followed by surgery, PET radiomic features could not predict histopathologic tumor response and survival. It is crucial to further explore the biologic mechanism underlying imaging-derived parameters and plan a large, prospective, multicenter study with standardized protocols for all phases of the process of radiomic analysis to validate radiomics before its use in clinical routine.

Background and Objective
This systematic literature review addresses model-based cost-effectiveness studies for therapy response monitoring with positron emission tomography (PET) generally combined with low-dose computed tomography (CT) for various cancer types. Given the known heterogeneity in therapy response events, studies should consider patient-level modelling rather than cohort-based modelling because of its flexibility in handling these events and the time to events. This review aims to identify the modelling methods used and includes a systematic assessment of the assumptions made in the current literature.

Methods
This study was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Information sources included electronic bibliographic databases, reference lists of review articles and contact with experts in the fields of nuclear medicine, health technology assessment and health economics. Eligibility criteria included peer-reviewed scientific publications and published grey literature. Literature searches, screening and critical appraisal were conducted by two reviewers independently. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) were used to assess the methodological quality. The Bias in Economic Evaluation (ECOBIAS) checklist was used to determine the risk of bias in the included publications.

Results
The search results included 2959 publications. The number of publications included for data extraction and synthesis was ten, representing eight unique studies. These studies addressed patients with lymphoma, advanced head and neck cancers, brain tumours, non-small cell lung cancer and cervical cancer. All studies addressed response to chemotherapy. No study evaluated response to immunotherapy. Most studies positioned PET/CT as an add-on modality and one study positioned PET/CT as a replacement for conventional imaging (X-ray and contrast-enhanced CT). Three studies reported decision-tree structures, four studies reported cohort-level state-transition models and one study reported a partitioned survival model. No patient-level models were reported. The simulation horizons adopted ranged from 1 year to lifetime. Most studies reported a probabilistic analysis, whereas two studies reported a deterministic analysis only. Two studies conducted a value of information analysis. Multiple studies did not adequately discuss model-specific aspects of bias. Most importantly and regularly observed were a high risk of structural assumptions bias, limited simulation horizon bias and wrong model bias.

Conclusions
Model-based cost-effectiveness analysis for therapy response monitoring with PET/CT was based on cohorts of patients instead of individual patients in the current literature. Therefore, the heterogeneity in therapy response events was commonly not addressed appropriately. Further research should include more advanced and patient-level modelling approaches to accurately represent the complex context of clinical practice and, therefore, to be meaningful to support decision making.

Registration
This review is registered in PROSPERO, the international prospective register of systematic reviews funded by the National Institute for Health Research, with CRD42023402581.

Background
In metastatic castration-resistant prostate cancer (mCRPC), using serum prostate-specific antigen (PSA) levels to evaluate treatment response is not always accurate. This study aimed to assess the efficacy of PSMA PET/CT at specific time points for evaluating treatment response and predicting survival in mCRPC patients, compared to PSA.

Methods
Sixty mCRPC patients underwent [18F]PSMA-1007 PET/CT at baseline and for treatment response evaluation of either androgen receptor-targeted agents (after 3 months) or chemotherapy (after completion), and were retrospectively analysed. Visual assessment categorised overall response and response of the worst responding lesion as partial response, stable disease, or progressive disease, using the EAU/EANM criteria. Additionally, percentage changes in SUVmax, total tumour volume and total lesion uptake (tumour volume * SUVmean) were calculated. PSA response was defined according to the PCWG3 criteria. Cox regression analysis identified predictors of overall survival.

Results
PSMA PET/CT and PSA response were discordant in 47 % of patients, and PSMA PET/CT response was worse in 89 % of these cases. Overall response on PSMA PET/CT independently predicted overall survival (progression versus non-progression: HR = 4.05, p < 0.001), outperforming PSA response (progression versus non-progression: HR = 2.53, p = 0.010) and other PSMA PET/CT parameters. Among patients with a PSA decline of > 50 %, 31 % showed progressive disease on PSMA PET/CT, correlating with higher mortality risk (progression versus non-progression: HR = 4.38, p = 0.008). No flare in PSMA uptake was observed in this cohort.

Conclusions
PSMA PET/CT for assessing treatment response at predefined time points was superior to PSA-based response for predicting overall survival in mCRPC patients treated with androgen receptor-targeted agents and chemotherapy. PSMA PET/CT showed the ability to detect disease progression earlier than PSA levels, which can affect treatment decisions and has the potential to improve patient outcomes. We recommend further research to validate these findings in larger patient cohorts, to extend the number of treatments, and to evaluate cost-effectiveness and impact on patient outcomes.

Background and aims
Immune checkpoint inhibitors (ICIs) revolutionized cancer treatment. However, ICIs may increase the immune response to non-tumor cells, possibly resulting in increased arterial inflammation, raising the risk of atherosclerotic events. Nevertheless, malignancies may induce a pro-inflammatory state and the association between ICIs and arterial inflammation remains to be clarified. This study aims to assess differences in increase in arterial inflammation between patients with advanced melanoma treated with ICIs compared to a control group without ICIs.

Methods
Patients with advanced melanoma who underwent [18F]FDG PET/CT scans at baseline, 6 months (T1) and 18 months (T2) were included in this retrospective observational study. Arterial inflammation was evaluated in eight segments by calculating the target-to-background ratio (TBR). The primary study outcome was the difference in increase in mean TBRmax between patients treated with and without ICIs.

Results
We included 132 patients of whom 72.7 % were treated with ICIs. After exclusion for the use of anti-inflammatory medication, patients treated with ICIs showed a significant increase in mean TBRmax between baseline and T1 from 1.29 ± 0.12 to 1.33 ± 0.13 (p = 0.017), while in the control group, no change in mean TBRmax (1.30 ± 0.12 to 1.28 ± 0.10, p = 0.22) was observed (p = 0.027). During longer follow-up, mean TBRmax remained stable in both groups. Arterial inflammation increased significantly after ICI therapy in patients without active inflammation (p < 0.001) and in patients without calcifications (p = 0.013).

Conclusions
A significant increase in arterial inflammation as measured on [18F]FDG PET/CT was observed in patients with advanced melanoma treated with ICIs only in the first six months after initiation of therapy, whereas no changes were observed in the control group. Moreover, arterial inflammation was mainly increased in patients without pre-existing inflammatory activity and with non-calcified lesions.

Purpose: Assessing renal perfusion in-vivo is challenging and quantitative information regarding renal hemodynamics is hardly incorporated in medical decision-making while abnormal renal hemodynamics might play a crucial role in the onset and progression of renal disease. Combining physiological stimuli with rubidium-82 positron emission tomography/computed tomography (⁸²Rb PET/CT) offers opportunities to test the kidney perfusion under various conditions. The aim of this study is: (1) to investigate the application of a one-tissue compartment model for measuring renal hemodynamics with dynamic ⁸²Rb PET/CT imaging, and (2) to evaluate whether dynamic PET/CT is sensitive to detect differences in renal hemodynamics in stress conditions compared to resting state. Methods: A one-tissue compartment model for the kidney was applied to cardiac ⁸²Rb PET/CT scans that were obtained for ischemia detection as part of clinical care. Retrospective data, collected from 17 patients undergoing dynamic myocardial ⁸²Rb PET/CT imaging in rest, were used to evaluate various CT-based volumes of interest (VOIs) of the kidney. Subsequently, retrospective data, collected from 10 patients (five impaired kidney functions and five controls) undergoing dynamic myocardial ⁸²Rb PET/CT imaging, were used to evaluate image-derived input functions (IDIFs), PET-based VOIs of the kidney, extraction fractions, and whether dynamic ⁸²Rb PET/CT can measure renal hemodynamics differences using the renal blood flow (RBF) values in rest and after exposure to adenosine pharmacological stress. Results: The delivery rate (K₁) values showed no significant (p = 0.14) difference between the mean standard deviation (SD) K₁ values using one CT-based VOI and the use of two, three, and four CT-based VOIs, respectively 2.01(0.32), 1.90(0.40), 1.93(0.39), and 1.94(0.40) mL/min/mL. The ratio between RBF in rest and RBF in pharmacological stress for the controls were overall significantly lower compared to the impaired kidney function group for both PET-based delineation methods (region growing and iso-contouring), with the smallest median interquartile range (IQR) of 0.40(0.28–0.66) and 0.96(0.62–1.15), respectively (p < 0.05). The K₁ of the impaired kidney function group were close to 1.0 mL/min/mL. Conclusions: This study demonstrated that obtaining renal K₁ and RBF values using ⁸²Rb PET/CT was feasible using a one-tissue compartment model. Applying iso-contouring as the PET-based VOI of the kidney and using AA as an IDIF is suggested for consideration in further studies. Dynamic ⁸²Rb PET/CT imaging showed significant differences in renal hemodynamics in rest compared to when exposed to adenosine. This indicates that dynamic ⁸²Rb PET/CT has potential to detect differences in renal hemodynamics in stress conditions compared to the resting state, and might be useful as a novel diagnostic tool for assessing renal perfusion.

Purpose
Tumor-targeted positron emission tomography (PET) and fluorescence-guided surgery (FGS) could address current challenges in pre- and intraoperative imaging of gastric cancer. Adequate selection of molecular imaging targets remains crucial for successful tumor visualization. This study evaluated the potential of integrin αvβ6, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM) and human epidermal growth factor receptor-2 (HER2) for molecular imaging of primary gastric cancer, as well as lymph node and distant metastases.

Methods
Expression of αvβ6, CEACAM5, EGFR, EpCAM and HER2 was determined using immunohistochemistry in human tissue specimens of primary gastric adenocarcinoma, healthy surrounding stomach, esophageal and duodenal tissue, tumor-positive and tumor-negative lymph nodes, and distant metastases, followed by quantification using the total immunostaining score (TIS).

Results
Positive biomarker expression in primary gastric tumors was observed in 86% for αvβ6, 72% for CEACAM5, 77% for EGFR, 93% for EpCAM and 71% for HER2. Tumor expression of CEACAM5, EGFR and EpCAM was higher compared to healthy stomach tissue expression, while this was not the case for αvβ6 and HER2. Tumor-positive lymph nodes could be distinguished from tumor-negative lymph nodes, with accuracy ranging from 82 to 93% between biomarkers. CEACAM5, EGFR and EpCAM were abundantly expressed on distant metastases, with expression in 88–95% of tissue specimens.

Conclusion
Our findings show that CEACAM5, EGFR and EpCAM are promising targets for molecular imaging of primary gastric cancer, as well as visualization of both lymph node and distant metastases. Further clinical evaluation of PET and FGS tracers targeting these antigens is warranted.

Purpose: The aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres (¹⁶⁶Ho-MS), when administered as adjuvant therapy after RFA of HCC 2–5 cm. The objective was to establish a treatment volume absorbed dose that results in an absorbed dose of ≥ 120 Gy on the hyperemic zone around the ablation necrosis (i.e., target volume). Methods: In this multicenter, prospective dose-escalation study in BCLC early stage HCC patients with lesions 2–5 cm, RFA was followed by (super-)selective infusion of ¹⁶⁶Ho-MS on day 5–10 after RFA. Dose distribution within the treatment volume was based on SPECT-CT. Cohorts of up to 10 patients were treated with an incremental dose (60 Gy, 90 Gy, 120 Gy) of ¹⁶⁶Ho-MS to the treatment volume. The primary endpoint was to obtain a target volume dose of ≥ 120 Gy in 9/10 patients within a cohort. Results: Twelve patients were treated (male 10; median age, 66.5 years (IQR, [64.3–71.7])) with a median tumor diameter of 2.7 cm (IQR, [2.1–4.0]). At a treatment volume absorbed dose of 90 Gy, the primary endpoint was met with a median absorbed target volume dose of 138 Gy (IQR, [127–145]). No local recurrences were found within 1-year follow-up. Conclusion: Adjuvant (super-)selective infusion of ¹⁶⁶Ho-MS after RFA for the treatment of HCC can be administered safely at a dose of 90 Gy to the treatment volume while reaching a dose of ≥ 120 Gy to the target volume and may be a favorable adjuvant therapy for HCC lesions 2–5 cm. Trial registration: Clinicaltrials.gov NCT03437382.

Purpose: We conducted a cost-effectiveness analysis in which we compared a preoperative [¹⁸F]Fluorocholine PET/CT-based one-stop-shop imaging strategy with current best practice in which [¹⁸F]Fluorocholine PET/CT is only recommended after negative or inconclusive [^99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT for patients suffering from primary hyperparathyroidism. We investigated whether the one-stop-shop strategy performs as well as current best practice but at lower costs. Methods: We developed a cohort-level state transition model to evaluate both imaging strategies respecting an intraoperative parathyroid hormone monitored treatment setting as well as a traditional treatment setting. The model reflects patients’ hospital journeys after biochemically diagnosed primary hyperparathyroidism. A cycle length of twelve months and a lifetime horizon were used. We conducted probabilistic analyses simulating 50,000 cohorts to assess joint parameter uncertainty. The incremental net monetary benefit and cost for each quality-adjusted life year were estimated. Furthermore, threshold analyses regarding the tariff of [¹⁸F]Fluorocholine PET/CT and the sensitivity of [^99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT were performed. Results: The simulated long-term health effects and costs were similar for both imaging strategies. Accordingly, there was no incremental net monetary benefit and the one-stop-shop strategy did not result in lower costs. These results applied to both treatment settings. The threshold analysis indicated that a tariff of €885 for [¹⁸F]Fluorocholine PET/CT was required to be cost-effective compared to current best practice. Conclusion: Both preoperative imaging strategies can be used interchangeably. Daily clinical practice grounds such as available local resources and patient preferences should inform policy-making on whether a hospital should implement the one-stop-shop imaging strategy.

Background: In the Netherlands, the COVID-19 pandemic resulted in a temporary halt of population screening for cancer and limited hospital capacity for non-COVID care. We aimed to investigate the impact of the pandemic on the in-hospital diagnostic pathway of breast cancer (BC) and colorectal cancer (CRC). Methods: 71,159 BC and 48,900 CRC patients were selected from the Netherlands Cancer Registry. Patients, diagnosed between January 2020 and July 2021, were divided into six periods and compared to the average of patients diagnosed in the same periods in 2017–2019. Diagnostic procedures performed were analysed using logistic regression. Lead time of the diagnostic pathway was analysed using Cox regression. Analyses were stratified for cancer type and corrected for age, sex (only CRC), stage and region. Results: For BC, less mammograms were performed during the first recovery period in 2020. More PET-CTs were performed during the first peak, first recovery and third peak period. For CRC, less ultrasounds and more CT scans and MRIs were performed during the first peak. Lead time decreased the most during the first peak by 2 days (BC) and 8 days (CRC). Significantly fewer patients, mainly in lower stages, were diagnosed with BC (−47%) and CRC (−36%) during the first peak. Conclusion: Significant impact of the COVID-19 pandemic was found on the diagnostic pathway, mainly during the first peak. In 2021, care returned to the same standards as before the pandemic. Long-term effects on patient outcomes are not known yet and will be the subject of future research.