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.

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 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: 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
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: In this pilot study, we investigated the feasibility of response prediction using digital [ 18 F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial. METHODS: Rectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and [ 18 F]FDG PET/CT before, 2 weeks into, and 6-8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P  ≤ 0.2, promising predictive features for response were selected. RESULTS: Nineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline [T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy], early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Δ maximum standardized uptake value, Δ peak standardized uptake value corrected for lean body mass), were promising features. CONCLUSION: Both multiparametric MRI and [ 18 F]FDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT.

Objective Since the end of 2019, the coronavirus disease 2019 (COVID-19) virus has infected millions of people, of whom a significant group suffers from sequelae from COVID-19, termed long COVID. As more and more patients emerge with long COVID who have symptoms of fatigue, myalgia and joint pain, we must examine potential biomarkers to find quantifiable parameters to define the underlying mechanisms and enable response monitoring. The aim of this study is to investigate the potential added value of [ ¹⁸F]FDG-PET/computed tomography (CT) for this group of long COVID patients. Methods For this proof of concept study, we evaluated [ ¹⁸F]FDG-PET/CT scans of long COVID patients and controls. Two analyses were performed: semi-quantitative analysis using target-to-background ratios (TBRs) in 24 targets and total vascular score (TVS) assessed by two independent nuclear medicine physicians. Mann-Whitney U-test was performed to find significant differences between the two groups. Results Thirteen patients were included in the long COVID group and 25 patients were included in the control group. No significant differences (P < 0.05) were found between the long COVID group and the control group in the TBR or TVS assessment. Conclusion As we found no quantitative difference in the TBR or TVS between long COVID patients and controls, we are unable to prove that [ ¹⁸F]FDG is of added value for long COVID patients with symptoms of myalgia or joint pain. Prospective cohort studies are necessary to understand the underlying mechanisms of long COVID.

Background: Accuracy and precision assessment in radiomic features is important for the determination of their potential to characterize cancer lesions. In this regard, simulation of different imaging conditions using specialized phantoms is increasingly being investigated. In this study, the design and evaluation of a modular multimodality imaging phantom to simulate heterogeneous uptake and enhancement patterns for radiomics quantification in hybrid imaging is presented. Methods: A modular multimodality imaging phantom was constructed that could simulate different patterns of heterogeneous uptake and enhancement patterns in positron emission tomography (PET), single-photon emission computed tomography (SPECT), computed tomography (CT), and magnetic resonance (MR) imaging. The phantom was designed to be used as an insert in the standard NEMA-NU2 IEC body phantom casing. The entire phantom insert is composed of three segments, each containing three separately fillable compartments. The fillable compartments between segments had different sizes in order to simulate heterogeneous patterns at different spatial scales. The compartments were separately filled with different ratios of 99mTc-pertechnetate, 18F-fluorodeoxyglucose ([18F]FDG), iodine- and gadolinium-based contrast agents for SPECT, PET, CT, and T1-weighted MR imaging respectively. Image acquisition was performed using standard oncological protocols on all modalities and repeated five times for repeatability assessment. A total of 93 radiomic features were calculated. Variability was assessed by determining the coefficient of quartile variation (CQV) of the features. Comparison of feature repeatability at different modalities and spatial scales was performed using Kruskal-Wallis-, Mann-Whitney U-, one-way ANOVA- and independent t-tests. Results: Heterogeneous uptake and enhancement could be simulated on all four imaging modalities. Radiomic features in SPECT were significantly less stable than in all other modalities. Features in PET were significantly less stable than in MR and CT. A total of 20 features, particularly in the gray-level co-occurrence matrix (GLCM) and gray-level run-length matrix (GLRLM) class, were found to be relatively stable in all four modalities for all three spatial scales of heterogeneous patterns (with CQV < 10%). Conclusion: The phantom was suitable for simulating heterogeneous uptake and enhancement patterns in [18F]FDG-PET, 99mTc-SPECT, CT, and T1-weighted MR images. The results of this work indicate that the phantom might be useful for the further development and optimization of imaging protocols for radiomic quantification in hybrid imaging modalities.

Background: Central necrosis can be detected on [¹⁸F]FDG PET/CT as a region with little to no tracer uptake. Currently, there is no consensus regarding the inclusion of regions of central necrosis during volume of interest (VOI) delineation for radiomic analysis. The aim of this study was to assess how central necrosis affects radiomic analysis in PET. Methods: Forty-three patients, either with non-small cell lung carcinomas (NSCLC, n = 12) or with pheochromocytomas or paragangliomas (PPGL, n = 31), were included retrospectively. VOIs were delineated with and without central necrosis. From all VOIs, 105 radiomic features were extracted. Differences in radiomic features between delineation methods were assessed using a paired t-test with Benjamini-Hochberg multiple testing correction. In the PPGL cohort, performances of the radiomic models to predict the noradrenergic biochemical profile were assessed by comparing the areas under the receiver operating characteristic curve (AUC) for both delineation methods. Results: At least 65% of the features showed significant differences between VOI_vital-tumour and VOI_gross-tumour (65%, 79% and 82% for the NSCLC, PPGL and combined cohort, respectively). The AUCs of the radiomic models were not significantly different between delineation methods. Conclusion: In both tumour types, almost two-third of the features were affected, demonstrating that the impact of whether or not to include central necrosis in the VOI on the radiomic feature values is significant. Nevertheless, predictive performances of both delineation methods were comparable. We recommend that radiomic studies should report whether or not central necrosis was included during delineation.