Background: Current diagnosis of Transthyretin-related Amyloidosis (ATTR) using bone scintigraphy is primarily based on visual scoring and semi-quantitative indices. With the introduction of new potential life-prolonging drugs for ATTR, a more precise quantification of myocardial amyloid burden is desirable for improved response prediction and therapy monitoring. Methods: At first, quantification experiments using an anthropomorphic thorax phantom were performed. Second, 32 patients underwent both planar whole body [^99mTc]- 3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD)-scintigraphy and quantitative Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) of the thorax. SPECT/CT standardized myocardial uptake values SUVpeak and SUVpeak normalized to bone uptake (nSUVpeak) were determined. Results: Phantom measurements showed a strong linear relationship between the activity in the myocardial insert and the measured activity (r = 0.9998, p = 0.01), but the measured activity was systematically underestimated by approximately 30%. Receiver operating characteristics (ROC) analysis revealed a 100% sensitivity and specificity at a cut-off of 3.1 for SUVpeak for the differentiation of both patient groups. Conclusion: SUV quantification of ATTR amyloid burden is feasible using novel SPECT/CT technology. With a SUVpeak cut-off of 3.1, patients with Perugini grade 2 and 3 could be clearly separated from those with Perugini grade 0 and 1. Besides ATTR diagnostics, quantification of amyloid deposits could potentially be used for therapy monitoring and prognostication in patients with cardiac ATTR.

Background: Large-scale data on the diagnostic performance of functional imaging in metastatic pheochromocytoma/paraganglioma (PPGL) are scarce. Objective: To analyze the diagnostic accuracy of functional imaging for the assessment of metastases during long-term follow-up (FU). Design: Retrospective cohort study, 1991–2025. Setting: Referral center. Outcomes: Sensitivity and specificity of ¹²³MIBG-, ¹⁸F-DOPA-, ⁶⁸GaDOTA-based and ¹⁸FDG PET/CT. Patients: Patients with metastatic PPGL and without PPGL, ≥1 functional imaging prior to first diagnosis and/or during FU and FU ≥ 3 months. Results: 59 ¹²³MIBG-, 101 ¹⁸F-DOPA-, 11 ¹⁸FDG- and 74 ⁶⁸GaDOTA-based PET/CT were performed in 57 patients with metastatic PPGL and 37 ¹²³MIBG-, 323 ¹⁸F-DOPA-, 259 ¹⁸FDG- and 641 ⁶⁸GaDOTA-based imaging in 527 patients without PPGL. FU was 11.6 ± 11.4 and 5.1 ± 4.7 years, respectively. Sensitivity for the detection of all metastases (total cohort) by patient-based analysis was comparable between ¹⁸F-DOPA (77%), both ⁶⁸GaDOTA-based tracers combined (67%) and ¹²³MIBG (72%); lesion-based analysis was better for ¹⁸F-DOPA (94%) than for ⁶⁸GaDOTA (85%) and ¹²³MIBG (67%). Specificity (patient- and lesion-based) of ¹⁸F-DOPA vs. ⁶⁸GaDOTA (96–99%) was comparable and better than ¹²³MIBG (73%) and ¹⁸FDG (75%). Conclusions: Sensitivity of ¹⁸F-DOPA was superior to ⁶⁸GaDOTA for the detection of all and bone metastases in the total cohort and in patients with PCC, that of ⁶⁸GaDOTA was better for bone metastases with PGL, specificity was comparable and for both was better than for ¹⁸FDG and ¹²³MIBG. Given the beneficial pharmaceutical properties and favorable diagnostic performance, ¹⁸F-DOPA may be a good alternative to ⁶⁸GaDOTA-based tracers for the functional imaging of metastatic PPGL.

BACKGROUND: Increasing evidence from preclinical models has linked the actions of brown adipose tissue (BAT) with protection against atherosclerosis and cardiovascular disease, in part due to its salutary effects on systemic lipid composition. However, human data on the role of BAT in atherosclerosis are scarce. METHODS: In this cross-sectional study, we examined 65 individuals with obesity and analyzed cold-induced BAT activity and vascular inflammation in the aorta using ¹⁸ F-fluorodeoxyglucose positron emission tomography combined with computed tomography in combination with systemic lipidomics and proteomics analyses. RESULTS: We identified 21 subjects with cold-induced BAT (BAT positive), whereas 44 individuals had no significant BAT activity (BAT negative) after cold exposure. Both groups had similar age, sex distribution, body mass index, and classical cardiovascular risk profile. However, BAT-positive individuals had significantly less arterial inflammation as evidenced by lower ¹⁸ F-fluorodeoxyglucose uptake in the ascending aorta and the aortic arch. Notably, BAT volume, SUV _mean (mean standardized uptake value), and cold-induced thermogenesis correlated negatively with aortic inflammation, suggesting an atheroprotective role of BAT. Using unbiased lipidomics and proteomics analyses in plasma, we found that anti-inflammatory and potentially antiatherogenic circulating factors, such as cytochrome P450 oxylipin products and the serpin family member SERPINB12 (serpin family B member 12), were increased in BAT positive, whereas proatherogenic and prothrombotic factors, including acute phase protein ORM2 (orosomucoid 2), APOD (apolipoprotein D), FGA (fibrinogen A), and FGB (fibrinogen B), were significantly lower in individuals with active BAT. Likewise, the circulating concentrations of inflammatory markers, such as IL-6 (interleukin-6), were reduced in BAT positive versus BAT negative. CONCLUSIONS: Together, these data link human BAT function with protection against arterial inflammation and a potentially antiatherogenic and anti-inflammatory circulating profile. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT02381483 and NCT03168009.

Obesity is linked to increased risk of cardiovascular disease, type 2 diabetes, and overall mortality. Bariatric surgery effectively achieves long-term weight loss, especially in clinically severe obesity. Postoperative weight loss is associated with increased N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, without signs of cardiac dysfunction. We investigated longitudinal changes in NT-proBNP levels following different bariatric procedures and examined their associations with metabolic alterations. This retrospective study was conducted in a large university hospital in central Europe using data from 2005 to 2016. We analyzed preoperative and postoperative laboratory results from 508 patients undergoing three different bariatric procedures. Follow-up records were available for 347 (68.3%) patients at month 3, 260 (51.2%) at month 6, 152 (29.9%) at month 9, 183 (36.0%) at month 12, 166 (32.7%) at month 18, and 127 (25.0%) at month 24 postsurgery. NT-proBNP levels rose shortly after bariatric surgery and remained elevated, with no significant differences between surgical types. Women exhibited significantly higher postoperative NT-proBNP concentrations than men. The increase in NT-proBNP correlated with improved insulin resistance but not with other metabolic parameters. We found no evidence supporting reduced renal clearance as a cause for elevated natriuretic peptides. Our data suggest a link between the NT-proBNP increase and reduced hyperinsulinemia following bariatric surgery, offering new insights into mechanisms underlying this frequent postoperative finding.

Context: Cold-induced activation of thermogenesis modulates energy metabolism, but the role of humoral mediators is not completely understood.Objective: To investigate the role of parathyroid and thyroid hormones in acute and adaptive response to cold in humans.Design: Cross-sectional study examining acute response to ice-water swimming and to experimental non-shivering thermogenesis (NST) induction in individuals acclimatized and non-acclimatized to cold. Seasonal variation in energy metabolism of ice-water swimmers and associations between circulating PTH and molecular components of thermogenic program in brown adipose tissue (BAT) of neck-surgery patients were evaluated.Setting: Clinical Research Center.Patients, Participants: Ice-water swimmers (winter swim n=15, NST-induction n=6), non-acclimatized volunteers (NST-induction, n=11, elective neck surgery n = 36).Main Outcomes and Results: In ice-water swimmers, PTH and TSH increased in response to 15min winter swim, while activation of NST failed to regulate PTH and lowered TSH. In non-acclimatized men, NST-induction decreased PTH and TSH. Positive correlation between systemic levels of PTH and whole-body metabolic preference for lipids as well as BAT 18F-FDG uptake was found across the two populations. Moreover, NST-cooling protocol-induced changes in metabolic preference for lipids correlated positively with changes in PTH. Finally, variability in circulating PTH correlated positively with UCP1/UCP1, PPARGC1A and DIO2 in BAT from neck surgery patients.Conclusions: Regulation of PTH and thyroid hormones during cold exposure in humans depends on the cold acclimatization level and/or cold stimulus intensity. Role of PTH in NST is substantiated by its positive relationships with whole-body metabolic preference for lipids, BAT volume and UCP1 content.

BACKGROUND: [¹⁷⁷Lu]Lu-prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) has demonstrated clinical efficacy in metastatic androgen pathway modulator-naïve (mAPMN) and metastatic castration-resistant prostate cancer (mCRPC), however treatment responses remain heterogeneous. PURPOSE: To evaluate the prognostic value of PSMA PET-derived imaging biomarkers and genomic alterations in relation to biochemical response and clinical outcomes in systemic therapy-naïve patients with mAPMN PCa receiving [¹⁷⁷Lu]Lu-PSMA RLT as first-line systemic therapy. METHODS: Systemic therapy-naïve patients with mAPMN PCa treated exclusively with [¹⁷⁷Lu]Lu-PSMA-RLT were retrospectively analyzed. Standardized uptake value (SUV) parameters (SUVmax, SUVmean, SUVpeak) and PSMA total tumor volume (PSMA-TTV) were derived from baseline and post-treatment [68Ga]Ga-PSMA-11 PET scans, with imaging response defined as a ≥30% reduction. Prostate-specific antigen (PSA) response, PSA-PFS and androgen deprivation therapy (ADT)-free survival were assessed. Available germline and somatic genomic alterations were analyzed for associations with outcomes. RESULTS: 26 patients were analyzed. Reductions ≥30% in SUVmax and PSMA-TTV were associated with prolonged PSA-PFS (27.1 vs. 9.4 months, p=0.01; 27.1 vs. 5.5 months, p< 0.001, respectively) and ADT-free survival (39.0 vs. 19.9 months, p=0.03; 23.9 vs. 13.8 months, p=0.028, respectively). In multivariable analysis, ΔPSMA-TTV ≥30% was independently associated with prolonged PSA-PFS (HR 0.23, 95% CI 0.08-0.68; p=0.008). Of 17 genomically profiled patients, nine had somatic alterations, most frequently involving TP53, MYC, NF1. Patients with altered DNA damage repair (DDR) pathway had lower baseline PSA (0.78 vs. 12.3 ng/mL; p=0.03) and SUVpeak (7.9 vs. 16.7; p=0.03). No other associations with genetic alteration status were observed. CONCLUSIONS: In systemic therapy-naïve patients with mAPMN PCa, reductions of ≥30% in SUVmax and PSMA-TTV following PSMA-RLT were associated with favorable outcomes, with ΔPSMA-TTV independently associated with prolonged PSA-PFS. PSMA PET-derived parameters may support treatment response assessment, whereas no prognostic association with genomic alterations was identified in this cohort.