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We report the case of a 69-year-old woman who underwent 18F-FDG PET/CT due to prolonged fever. One month before, the patient was diagnosed with COVID-19 infection. The 18F-FDG PET/CT showed several subcutaneous nodules with 18F-FDG uptake on the thorax and upper extremities and bilateral lung infiltrates due to organizing pneumonitis. Clinical examination revealed multiple tender nodules on thorax, arms, and legs, consistent with erythema nodosum (EN) induced by COVID-19 infection. The woman was treated with prednisone with a good effect on EN. To our knowledge, this is the first report on EN secondary to COVID-19 infection diagnosed on 18F-FDG PET/CT.

The fragmentation patterns of whole genome sequenced cell-free DNA are promising features for tumor-agnostic cancer detection. However, systematic biases challenge their cross-cohort generalization. We introduce LIONHEART, an open source cancer detection method specifically optimized to generalize across datasets. The method correlates bias-corrected cfDNA fragment coverage across the genome with the locations of accessible chromatin regions from 898 cell and tissue type features. We use these correlations to detect changes in the cell-free DNA cell type composition caused by cancer. We test LIONHEART on nine datasets and fourteen cancer types (1106 non-cancer controls, 1449 cancers) obtained from different studies and show that it can distinguish cancer samples from non-cancer controls across cohorts with ROC AUC scores ranging from 0.62-0.95 (mean = 0.83, std = 0.12). We further validate the method on an external dataset, achieving a ROC AUC of 0.917. Fragmentation patterns of cell-free DNA are a promising biomarker source, however, correlations with different cancer types are heterogenous. Here, the authors develop LIONHEART to enable detection of 14+ cancer types from whole genome sequenced cell-free DNA.

Background Circular RNAs (circRNAs) constitute a largely unexplored source for biomarker discovery in prostate cancer (PC). Here, we characterize the biomarker potential of circRNAs in PC, where the need for novel diagnostic and prognostic tools to facilitate more personalized management is pressing. Methods We profiled the transcriptomic landscape of circRNAs in PC by total RNA sequencing of 31 adjacent-normal and 143 tumor samples from localized (radical prostatectomy (RP)) and metastatic PC patients (cohort 1, training). Diagnostic and prognostic potential was evaluated in cohort 1, and 39 top circRNA candidates were selected for validation in two additional PC cohorts (cohort 2, n = 111; RP cohort 3, n = 191) by NanoString-based expression analysis. Biochemical recurrence (BCR)-free survival was assessed using Kaplan-Meier, univariate, and multivariate Cox regression analyses. The circRNA candidates were further detected in extracellular vesicle (EV)-enriched plasma samples from PC patients and controls (cohort 4, n = 54). Results Expression of circABCC4, circFAT3, circATRNL1, and circITGA7 was highly cancer-specific (area under the curve 0.71–0.86), while low circITGA7 expression was significantly ( P < 0.05) associated with BCR in univariate analysis in two RP cohorts. Moreover, we successfully trained and validated a novel 5-circRNA prognostic signature (circKMD1A/circTULP4/circZNF532/circSUMF1/circMKLN1) significantly associated with BCR beyond routine clinicopathological variables (RP cohort 1: P = 0.02, hazard ratio = 2.1; RP cohort 3: P < 0.001, hazard ratio = 2.1). Lastly, we provide proof-of-principle for detection of candidate circRNAs in EV-enriched plasma samples from PC patients. Conclusions circRNAs hold great biomarker potential in PC and display both high cancer specificity and association to disease progression.

Background/Objectives: Type 2 Diabetes Mellitus (T2DM) represents a significant global health burden, frequently leading to severe complications such as peripheral neuropathy and both micro- and macrovascular dysfunctions. These complications are integral to the pathology of diabetic foot ulcers (DFUs) and are associated with an elevated risk of lower limb amputations. This study investigated lower extremity skeletal muscle perfusion in patients with T2DM and DFUs using [15O]H2O PET imaging, in comparison to healthy controls. Methods: A total of 10 healthy controls and 26 patients with T2DM and DFUs were enrolled. Resting skeletal muscle perfusion was quantified using [15O]H2O PET. Regional perfusion was assessed in multiple lower leg and foot muscle groups. Distal blood pressure was measured, and foot/leg perfusion ratios were calculated. Results: Patients with T2DM and DFUs exhibited a 58% higher median global foot resting perfusion compared to healthy controls. At the individual muscle level, median perfusion in the flexor hallucis brevis was elevated by up to 210% in the ulcerated foot compared to controls. No significant differences in perfusion were observed in the non-ulcerated foot. The foot/leg perfusion ratio was up to 58% higher in the ulcerated limb of T2DM patients compared to the controls. Conclusions: This study demonstrates localized alterations in skeletal muscle perfusion in patients with T2DM and DFUs, characterized by elevated resting foot perfusion in muscles adjacent to ulcerations. Understanding these perfusion dynamics may contribute to refined DFU management strategies. However, further research is needed to validate the clinical utility of [15O]H2O PET imaging in guiding interventions and predicting treatment outcomes for DFUs.

Background [ 15 O]H 2 O PET/CT allows noninvasive quantification of tissue perfusion and can potentially play a future role in the diagnosis and treatment of peripheral artery disease. We aimed to evaluate the reliability of dynamic [ 15 O]H 2 O PET imaging for measuring lower extremity skeletal muscle perfusion. Ten healthy participants underwent same-day test–retest study with six dynamic [ 15 O]H 2 O PET scans of lower legs and feet. Manual volume-of-interests were drawn in skeletal muscles, and PET time activity curves were extracted. K 1 values (mL/min/100 mL) were estimated using a single-tissue compartment model (1TCM), autoradiography (ARG), and parametric imaging with blood input functions obtained from separate heart scans. Results Resting perfusion values in the muscle groups of the lower legs ranged from 1.18 to 5.38 mL/min/100 mL (ARG method). In the muscle groups of the feet, perfusion values ranged from 0.41 to 3.41 mL/min/100 mL (ARG method). Test–retest scans demonstrated a strong correlation and good repeatability for skeletal muscle perfusion with an intraclass correlation coefficient (ICC) of 0.88 and 0.87 and a repeatability coefficient of 34% and 53% for lower legs and feet, respectively. An excellent correlation was demonstrated when comparing volume-of-interest-based methods (1TCM and ARG) (lower legs: ICC = 0.96, feet: ICC = 0.99). Parametric images were in excellent agreement with the volume-of-interest-based ARG method (lower legs: ICC = 0.97, feet: ICC = 0.98). Conclusion Parametric images and volume-of-interest-based methods demonstrated comparable resting perfusion values in the lower legs and feet of healthy individuals. The largest variation was seen between individuals, whereas a smaller variation was seen between muscle groups. Repeated measurements of resting blood flow yielded a strong overall correlation for all methods.

Background/Objectives: The SENTIREC-endo study identified a safe sentinel lymph node mapping algorithm combined with PET-positive node dissection, matching radical pelvic and paraaortic lymphadenectomy in high-risk endometrial cancer. The present study evaluated the diagnostic accuracy of FDG-PET/CT for lymph node metastases in the same population based on location, size, and Standardised Uptake Value (SUV), in addition to assessing interrater agreement across three Danish centres. Methods: This prospective multicentre study included women with high-risk endometrial cancer from the Danish SENTIREC study database (2017–2023). All patients underwent preoperative FDG-PET/CT. Diagnostic accuracy was evaluated against a pathology-confirmed reference standard. Interrater agreement was evaluated between trained specialists in Nuclear Medicine. Results: Among 227 patients, 52 patients (23%) had lymph node metastases. FDG-PET/CT identified lymph node metastases with 56% sensitivity (95% CI: 42–68) and 91% specificity (95% CI: 86–94). Positive and negative predictive values were 64% and 87%, respectively. Specificity for paraaortic nodes was high (97%), though sensitivity remained limited (56%). Lymph node size and SUVmax had moderate diagnostic value (AUC-ROC ~0.7). Interrater proportion of agreement was 95% and Cohen’s Kappa κ = 0.84 (95% CI: 0.73–0.94), the latter of which was ‘almost perfect’. Conclusions: FDG-PET/CT had limited sensitivity in lymph node staging in high-risk EC, and the diagnostic accuracy of FDG-PET/CT remains complementary to the sentinel node procedure. Due to its high specificity and strong interrater reliability, FDG-PET/CT is recommended for clinical implementation in combination with the sensitive sentinel node biopsy for the targeted dissection of PET-positive lymph nodes, particularly in paraaortic regions.

PurposeTumour blood flow (TBF) is a crucial determinant of cancer growth. Recently, we validated Rubidium-82 (82Rb) positron emission tomography (PET) for TBF measurement in prostate cancer (PCa) and found TBF and cancer aggressiveness positively correlated. The aims of the present study were to determine the ability of TBF for separating significant from insignificant PCa and to examine the relation to underlying Na+/K+-ATPase density, which is relevant as 82Rb is transported intracellularly via the Na+/K+-ATPase.MethodsOne hundred and two patients were included for pelvic 82Rb PET scan prior to magnetic resonance imaging (MRI)-guided prostate biopsy. Findings constituted 100 PCa lesions (86 patients) and 25 benign lesions (16 patients). Tumours were defined on MRI and transferred to 82Rb PET for TBF measurement. Immunohistochemical Na+/K+-ATPase staining was subsequently performed on biopsies.ResultsTBF was the superior predictor (rho = 0.68, p < 0.0001, inflammatory lesions excluded) of MRI-guided biopsy grade group (GG) over lowest apparent diffusion coefficient (ADC) value (rho = −0.23, p = 0.01), independent of ADC value and tumour volume (p < 0.0001). PET could separate GG-2-5 from GG-1 and benign lesions with an area under the curve (AUC), sensitivity, and specificity of 0.79, 96%, and 59%, respectively. For separating GG-3-5 from GG-1-2 and benign lesions the AUC, sensitivity, and specificity were 0.82, 95%, and 63%, respectively. Na+/K+-ATPase density per PCa cell profile was 38% lower compared with that of the benign prostate cell profiles. Neither cell density nor Na+/K+-ATPase density determined tumour 82Rb uptake.ConclusionTBF is an independent predictor of PCa aggressiveness and deserves more attention, as it may be valuable in separating clinically significant from insignificant PCa.

BackgroundBoth prostate-specific membrane antigen (PSMA) uptake and tumour blood flow (TBF) correlate with International Society of Urological Pathology (ISUP) Grade Group (GG) and hence prostate cancer (PCa) aggressiveness. The aim of the present study was to evaluate the potential synergistic benefit of combining the two physiologic parameters for separating significant PCa from insignificant findings.MethodsFrom previous studies of [82Rb]Rb positron emission tomography (PET) TBF in PCa, the 43 patients that underwent clinical [68Ga]Ga-PSMA-11 PET were selected for this retrospective study. Tumours were delineated on [68Ga]Ga-PSMA-11 PET or magnetic resonance imaging. ISUP GG was recorded from 52 lesions.Results[68Ga]Ga-PSMA-11 maximum standardized uptake value (SUVmax) and [82Rb]Rb SUVmax correlated moderately with ISUP GG (rho = 0.59 and rho = 0.56, both p < 0.001) and with each other (r = 0.65, p < 0.001). A combined model of [68Ga]Ga-PSMA-11 and [82Rb]Rb SUVmax separated ISUP GG > 2 from ISUP GG 1–2 and benign with an area-under-the-curve of 0.85, 96% sensitivity, 74% specificity, and 95% negative predictive value. The combined model performed significantly better than either tracer alone did (p < 0.001), primarily by reducing false negatives from five or six to one (p ≤ 0.025).ConclusionPSMA uptake and TBF provide complementary information about tumour aggressiveness. We suggest that a combined analysis of PSMA uptake and TBF could significantly improve the negative predictive value and allow non-invasive separation of significant from insignificant PCa.

A 76-year-old man with newly diagnosed high-risk prostate cancer was referred for primary staging with F-18-PSMA-1007 PET/CT. The PET/CT scan showed no lymph node or bone metastases, only localized disease within the prostate gland. Additionally, the F-18-PSMA PET/CT scan showed a PSMA-positive lesion correlating to a polyp located in the body of the stomach on the greater curvature. A prior F-18-FDG PET/CT showed low FDG uptake in the polyp, but this was not reported initially in the written report. The patient had no upper gastrointestinal symptoms. A gastroscopy with biopsies was performed, and the histopathology results showed chronic unspecific inflammation with no granulomas, dysplastic or malignant changes in three out of three biopsies. A repeated gastroscopy with biopsy showed an epithelioid variant of a gastrointestinal stromal tumor (Ki-67 index 2%). A laparoscopic tumor extirpation was planned after radiation treatment in combination with endocrine therapy of the localized prostate cancer. To our knowledge, this is one of very few reported cases of a PSMA-positive gastrointestinal stromal tumor (GIST), and can be added to the list of malignant pitfalls of PSMA PET/CT in prostate cancer patients.

Background Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and prolonged QRS duration where a biventricular pacemaker is implanted to achieve faster activation and more synchronous contraction of the left ventricle (LV). Despite the convincing effect of CRT, 30–40% of patients do not respond. Among the most important correctable causes of non-response to CRT is non-optimal LV lead position. Methods We will enroll 122 patients in this patient-blinded and assessor-blinded, randomized, clinical trial aiming to investigate if implanting the LV lead guided by electrical mapping towards the latest LV activation as compared with imaging-guided implantation, causes an excess increase in left ventricular (LV) ejection fraction (LVEF). The patients are randomly assigned to either the intervention group: preceded by cardiac computed tomography of the cardiac venous anatomy, the LV lead is placed according to the latest LV activation in the coronary sinus (CS) branches identified by systematic electrical mapping of the CS at implantation and post-implant optimization of the interventricular pacing delay; or patients are assigned to the control group: placement of the LV lead guided by cardiac imaging. The LV lead is targeted towards the latest mechanical LV activation as identified by echocardiography and outside myocardial scar as identified by myocardial perfusion (MP) imaging. The primary endpoint is change in LVEF at 6-month follow up (6MFU) as compared with baseline measured by two-dimensional echocardiography. Secondary endpoints include relative percentage reduction in LV end-systolic volume, all-cause mortality, hospitalization for heart failure, and a clinical combined endpoint of response to CRT at 6MFU defined as the patient being alive, not hospitalized for heart failure, and experiencing improvement in NYHA functional class or/and > 10% increase in 6-minute walk test. Discussion We assume an absolute increase in LVEF of 12% in the intervention group versus 8% in the control group. If an excess increase in LVEF can be achieved by LV lead implantation guided by electrical mapping, this study supports the conduct of larger trials investigating the impact of this strategy for LV-lead implantation on clinical outcomes in patients treated with CRT. Trial registration ClinicalTrials.gov, NCT02346097 . Registered on 12 January 2015. Patients were enrolled between 16 February 2015 and 13 December 2017.