Metastatic pheochromocytomas and paragangliomas (mPPGLs) are rare neuroendocrine tumours with limited therapeutic options. Peptide receptor radionuclide therapy (PRRT) using somatostatin receptor (SSTR) antagonists (e.g. [177Lu]Lu-DOTA-JR11) may achieve higher tumour and organ absorbed doses compared with standard SSTR agonist therapy (e.g. [177Lu]Lu-DOTA-TOC). This study aimed to perform an intra-patient comparison of tumour and organ dosimetry between [177Lu]Lu-DOTA-TOC and [177Lu]Lu-DOTA-JR11 in patients with mPPGLs refractory to conventional therapies. Secondary endpoints included safety and exploratory clinical efficacy of [177Lu]Lu-DOTA-JR11. In this retrospective pilot study, 6 patients with mPPGLs received 1–2 cycles of [177Lu]Lu-DOTA-TOC ( 7.4 GBq/cycle), followed by 1–2 cycles of [177Lu]Lu-DOTA-JR11 (2 GBq/m2 × body surface area) at an interval of 10–12 weeks. Endpoints included estimation of tumour and organ absorbed doses, assessment of safety according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and symptoms, and evaluation of progression-free survival (PFS) before and after [177Lu]Lu-DOTA-JR11 therapy. Intra-patient comparison showed that the median tumour absorbed dose per cycle was 1.3-fold higher (range 0.9–3.5) with [177Lu]Lu-DOTA-JR11 than with [177Lu]Lu-DOTA-TOC. This was associated with longer PFS after [177Lu]Lu-DOTA-JR11 (12.5 months; range 6 – >20) versus PFS before inclusion (3.5 months; range 1–9). The most severe adverse event was grade 3 lymphopenia in one patient. No thrombocytopenia, neutropenia, creatinine elevation or alanine aminotransferase elevation was observed. [177Lu]Lu-DOTA-JR11 resulted in higher tumour absorbed doses than [177Lu]Lu-DOTA-TOC and was associated with longer post-treatment PFS than PFS before inclusion in this small cohort. Treatment was well tolerated, supporting further prospective evaluation in patients with mPPGLs.

INTRODUCTION:Myocardial perfusion imaging (MPI) is widely used to assess coronary artery disease (CAD). U.S. studies have reported increasing normal MPI findings over time. However, European data are limited. This study examined temporal trends in pre-test probability (PTP) and MPI findings at a large Swiss centre. METHODS AND RESULTS:In this retrospective study, 45 686 MPI scans were analysed. Clinical data included demographics, symptoms, risk factors, MPI results, and coronary artery calcium score (CACS). Endpoints were defined as abnormal MPI (Summed Stress Score ≥4), small ischaemia (Summed Difference Score ≥2), and relevant ischaemia (≥10% ischaemia). PTP was calculated using the 2013/2019 ESC chronic coronary syndrome (CCS) guidelines, and risk factor-weighted clinical likelihood (RF-CL) from the 2024 guidelines. Normal MPI results increased significantly over time (53% (2000) → 66% (2024), P < 0.001), irrespective of unchanged PTP/RF-CL, modality, type of stress, symptoms and risk factors. Small ischaemia decreased (37.6% → 34.2%), while relevant ischaemia increased (11.0% → 13.2%, P < 0.001 each) slightly. SSS and SRS decreased significantly, whereas SDS remained unchanged. CACS and the prevalence of zero CACS remained unchanged over time. ESC PTP models overestimated the prevalence of abnormal MPI and small ischaemia. Only RF-CL predicted relevant ischaemia correctly in very low-risk patients. CONCLUSION:The rate of normal MPI results increased over time, but the trend was less pronounced than previously published. Possible explanations include referral of healthier patients (unchanged CACS despite increasing age), less typical angina, a lower prevalence of established CAD, and more female patients.

Introduction and objectives: Gatekeeper strategies using risk factor-weighted clinical likelihood (RF-CL), alone or combined with coronary artery calcium score-weighted clinical likelihood (CACS-CL), may reduce the number of normal scans, radiation exposure, and health care costs.Methods: Three diagnostic algorithms based on RF-CL and CACS-CL were evaluated in 1792 patients (mean age 65 ± 11 years; 43% female) referred for rubidium-82 (^82Rb) positron emission tomography (PET). Algorithm 1 deferred testing if RF-CL ≤ 5%. Algorithm 2 reclassified patients with RF-CL > 5%-15% using CACS-CL and deferred testing if either RF-CL or CACS-CL was ≤ 5%. Algorithm 3 deferred testing if CACS-CL ≤ 5%. Missed diagnoses, normal scans, radiation exposure, and costs were compared with the current reference standard (CACS + PET). Endpoints were defined as small ischemia (summed difference score [SDS] ≥ 2) and relevant ischemia (≥ 10% of the myocardium).Results: Median RF-CL and CACS-CL were 11% [6-19] and 12% [3-28], respectively. Algorithm 1 reduced radiation exposure and costs by 22.0% while maintaining high gatekeeper performance (sensitivity/negative predictive value [NPV]: 92.7%/98.2%). Algorithm 2 deferred the largest proportion of patients (36.4%) but missed small ischemia in 2.0%. Algorithm 3 demonstrated the best overall gatekeeper performance, reducing radiation exposure by 28.7% and costs by 29.7% without compromising diagnostic accuracy (sensitivity/NPV: 93.2%/98.4% for small ischemia and 97.0%/99.7% for relevant ischemia).Conclusions: Refining RF-CL in all patients and deferring testing when CACS-CL ≤ 5% provided the most effective gatekeeper strategy in patients with suspected chronic coronary syndromes.

Brown adipose tissue (BAT) can increase whole-body energy expenditure (EE) and is associated with metabolic health, making it a promising pharmacologic target. In rodents, BAT activation by norepinephrine is mainly mediated by beta3-adrenergic receptor (AR) stimulation. However, recent evidence suggests that, in humans, the beta2-AR may be more important for the activation of BAT than the beta3-AR. We investigated in 12 healthy volunteers whether the specific beta2-AR agonist fenoterol activates human BAT comparable to the natural stimulus, cold exposure. Both interventions robustly increased EE, but only cold exposure activated BAT as assessed by FDG uptake. RNA sequencing (RNA-seq) analysis of human BAT revealed that the expression of beta3-AR, but not of beta2-AR, correlates with the expression of UCP1, the hallmark of thermogenic brown adipocytes. Our data indicate that the beta2-AR is not the main activating receptor of human BAT and suggest that beta2-AR agonism increases EE in tissues other than BAT.

Somatostatin receptor PET imaging is integral to the management of patients with neuroendocrine tumours (NETs), yet standardised criteria for therapy response assessment with the use of this modality are not available. This Policy Review reports the development of the European Neuroendocrine Tumor Society somatostatin receptor PET response assessment framework, established through a structured modified Delphi process coordinated by the European Neuroendocrine Tumor Society. 34 international experts from nuclear medicine, radiology, oncology, endocrinology, surgery, and related disciplines participated in four iterative rounds evaluating 76 statements, with consensus defined as at least 75% agreement. The framework proposes response categorisation based primarily on volumetric changes in somatostatin receptor-expressing target lesions, complemented by assessment of new lesions, rather than reliance on standardised uptake value-based metrics. Partial response is defined by at least 40% reduction in target lesion volume without new lesions, whereas progressive disease is defined by at least 40% volume increase of target lesions or the emergence of new lesions. Complete response requires absence of pathological tracer uptake, and a category of unconfirmed progressive disease is introduced for equivocal cases warranting short-interval reassessment. Although not yet validated against survival outcomes, this expert-derived framework (SSTR-PeRForm) provides a pragmatic foundation for harmonising somatostatin receptor PET-based response assessment in clinical trials and routine practice and represents a key step towards outcome-based validation.

Background Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is the leading theranostic strategy for metastatic castration-resistant prostate cancer (mCRPC). Randomised trials have shown survival benefit with [177Lu]Lu-PSMA-617, but prospective multicentre real-world data for the widely used alternative ligand [177Lu]Lu-PSMA-I&T remain scarce. In this study, we evaluated the safety and clinical activity of [177Lu]Lu-PSMA-I&T in routine practice. Methods This prospective, multicentre, Swiss registry enrolled consecutive men older than 18 years with histologically confirmed prostate adenocarcinoma undergoing intravenous [177Lu]Lu-PSMA-I&T therapy (7 GBq every 6 weeks for up to six cycles). Eligible patients had Eastern Cooperative Oncology Group performance status of 2 or less and PSMA-positive mCRPC with progressive disease after androgen receptor pathway inhibitor therapy or chemotherapy, or both, unless deemed unfit. The primary outcome was safety, assessed by treatment-emergent adverse events graded according to Common Terminology Criteria for Adverse Events (version 5.0). Assessments were performed at predefined timepoints before each treatment cycle and during the post-therapy follow-up. Secondary outcomes included the best prostate-specific antigen (PSA) response and PSA decline of 50% or more (PSA50) response according to the Prostate Cancer Working Group 3 criteria. All patients who underwent at least one treatment cycle were included in the final analysis of the observational registry. This study is registered at ClinicalTrials.gov, NCT06830408. Findings Between May 25, 2020, and June 4, 2024, 333 patients with mCRPC received [177Lu]Lu-PSMA-I&T therapy and were included in the analysis. The median follow-up was 12·0 months (IQR 6·5–20·0). Grade 3 treatment-emergent haematological toxicities included anaemia in 26 (8·8%; 95% CI 5·8–12·6) of 295, thrombocytopenia in nine (3·1%; 1·4–5·7) of 295, leukopenia in five (1·7%; 0·6–3·9) of 295, lymphopenia in 54 (21·1%; 16·3–26·6) of 256, and neutropenia in one (0·4%; 0·0–2·2) of 256. No grade 3 or worse renal toxicity or grade 4–5 treatment-emergent adverse events were observed. Best PSA response was achieved in 198 (64·3%; 95% CI 58·7–69·6) of 308 patients and PSA50 in 137 (44·5%; 38·8–50·2). Interpretation [177Lu]Lu-PSMA-I&T showed clinically meaningful activity with a favourable safety profile in heavily pretreated mCRPC. These findings provide prospective evidence supporting the safety and activity of PSMA-targeted radioligand therapy with [177Lu]Lu-PSMA-I&T in routine clinical practice. Funding Swiss Hadron Foundation.

Introducción y objetivos: La utilización de la probabilidad clínica ponderada por factores de riesgo (RF-CL) y su combinación con la puntuación de calcio arterial coronario (CACS-CL) podrían reducir las exploraciones normales, la exposición a radiación y los costes.Métodos: Se estudiaron 3 algoritmos diagnósticos que utilizan la RF-CL y CACS-CL en 1.792 pacientes (65 ± 11 años, 43% mujeres) derivados para realización de tomografía por emisión de positrones (PET) con rubidio-82 (82Rb). Algoritmo 1: aplazar la prueba si RF-CL ≤ 5%; algoritmo 2: reclasificar con CACS-CL si RF-CL > 5-15% y aplazar si RF-CL o CACS-CL ≤ 5%, y algoritmo 3: aplazar si CACS-CL ≤ 5%. Se compararon los diagnósticos perdidos, las exploraciones normales, la exposición a radiación y los costes frente al estándar de referencia actual (CACS + PET). Los parámetros de evaluación fueron la isquemia pequeña (suma de la puntuación diferencial [SPD] ≥ 2) y la relevante (≥ 10% del miocardio).Resultados: La mediana de la RF-CL y CACS-CL fue del 11 [6-19] y del 12% [3-28], respectivamente. El algoritmo 1 redujo la exposición a radiación y costes en un 22,0%, manteniendo una alta precisión en el rendimiento del cribado (sensibilidad/valor predictivo negativo [VPN] del 92,7/98,2%). El algoritmo 2 aplazó la mayor proporción de pacientes (36,4%), pero pasó por alto la isquemia leve en el 2,0%. El algoritmo 3 demostró el mejor rendimiento reduciendo la exposición a radiación y los costes en un 28,7 y 29,7%, respectivamente, sin comprometer la precisión (sensibilidad/VPN del 93,2/98,4% para la isquemia leve y del 97,0/99,7% para la relevante).Conclusiones: El refinamiento de la RF-CL en todos los pacientes y el aplazamiento si la CACS-CL ≤ 5% proporcionaron el mejor rendimiento de cribado ante la sospecha de síndrome coronario crónico.

Peptide Receptor Radionuclide Therapy (PRRT) with [177Lu]Lu-DOTA-TOC or [177Lu]Lu-DOTA-TATE provides limited response durability in neuroendocrine tumours (NETs). The somatostatin receptor subtype 2 (SSTR2) antagonist [177Lu]Lu-DOTA-JR11 may deliver higher tumour absorbed doses and enhanced efficacy. This study compared median progression-free survival (PFS) and disease control rate (DCR) after [177Lu]Lu-DOTA-JR11 rechallenge versus prior [177Lu]Lu-DOTA-TOC in the same patients with early-progressing metastatic NET. In this retrospective, single-centre compassionate-use study, 15 consecutive patients with metastatic NET who progressed ≤ 12 months after standard [177Lu]Lu-DOTA-TOC therapy (2–4 cycles; 5.6–7.5 GBq/cycle) received rechallenge PRRT: 1–2 cycles [177Lu]Lu-DOTA-TOC followed by 1–2 cycles [177Lu]Lu-DOTA-JR11 (2 GBq/m² body surface area; 2.8–4.8 GBq/cycle) at 10 ± 1 week intervals. Endpoints included comparison of median PFS, DCR, safety (CTCAE v5.0), and absorbed doses. Median PFS was 11 months (12-month DCR 20

Background/Purpose: Rectal neuroendocrine tumors (NETs) with distant metastases are uncommon, and evidence supporting the effectiveness of peptide receptor radionuclide therapy (PRRT) in this population remains limited, particularly in Asian cohorts. This study aimed to evaluate the clinical role and real-world outcomes of PRRT in Japanese patients with somatostatin receptor-positive metastatic rectal NETs. Methods: We retrospectively analyzed 20 patients with metastatic rectal NETs who underwent PRRT at the University Hospital Basel (Switzerland) and Yokohama City University Hospital (Japan) between April 2015 and May 2023. The primary endpoint was progression-free survival (PFS), and secondary endpoints included disease control rate (DCR), overall response rate (ORR), overall survival (OS), and adverse events (AEs). Exploratory subgroup analyses were performed according to clinical characteristics, including changes in serum neuron-specific enolase (NSE). Results: The median PFS was 18.9 months (95% CI, 13.5-24.3), and the median OS was 30.3 months (95% CI, 18.9-41.7). The DCR was 80.0%, and the ORR was 15.0%. Treatment responses included partial response in 3 patients, stable disease in 13, progressive disease in 3, and not evaluable in 1. The most common AEs were lymphopenia and anemia, and no secondary malignancies were observed. No clinical factors were significantly associated with PFS; however, higher baseline NSE levels showed a trend toward shorter PFS. Patients with post-treatment declines in NSE showed more favorable treatment responses. Conclusions: PRRT may provide durable disease control with a favorable safety profile in Japanese patients with metastatic rectal NETs. However, these findings should be interpreted with caution given the small sample size and heterogeneous patient population. Baseline NSE elevation and early post-treatment declines may serve as potential prognostic indicators. These results are hypothesis-generating and warrant validation in larger, multicenter studies.

CONTEXT:Insulinomas are the main cause of endogenous hyperinsulinemic hypoglycemia (EHH) in adults, with surgery as the only cure. Pancreas-preserving surgery is preferred, making precise preoperative localization crucial. GLP-1R-targeted imaging, such as [68Ga]Ga-DOTA-exendin-4 PET/CT, outperforms other imaging procedures for insulinoma localization. OBJECTIVE:To investigate the performance and clinical impact of [68Ga]Ga-DOTA-exendin-4 PET/CT for the detection of insulinomas in patients with EHH and prior negative or inconclusive conventional imaging. METHODS:In this retrospective, real-world, dual-center imaging study, 101 patients with biochemically proven EHH and/or a positive Whipple's triad underwent [68Ga]Ga-DOTA-exendin-4 PET/CT at two tertiary centers between April 2017 and March 2024. Among these, 58 patients with prior negative or inconclusive conventional imaging constituted the primary analysis cohort. Endpoints: Insulinoma detection rate and sensitivity by [68Ga]Ga-DOTA-exendin-4 PET/CT after negative or inconclusive conventional imaging and impact on clinical management. RESULTS:Among the 58 patients with prior negative or inconclusive conventional imaging, [68Ga]Ga-DOTA-exendin-4 PET/CT was positive in 42 patients, corresponding to a detection rate of 72% (95% CI, 59-83%). Thirty patients subsequently underwent PET/CT-guided surgery. Overall, 32 patients had histological verification (including two PET/CT-negative cases), corresponding to a sensitivity of 93.8% (95% CI, 79-99%). CONCLUSION:In real-world clinical practice, [68Ga]Ga-DOTA-exendin-4 PET/CT provides a high detection rate of 72% for localizing insulinomas, including one case of diffuse nesidioblastosis in patients with EHH and prior negative or inconclusive conventional imaging, thereby enabling PET/CT-guided surgical approaches. These findings underscore the substantial clinical impact of GLP-1R-targeted PET/CT on patient management and prognosis.GLP-1 receptor.

The goal of this phase 0 study was to determine the absorbed doses in tumors and relevant organs after a test injection of [161Tb]Tb-DOTA-LM3 and [177Lu]Lu-DOTATOC in the same cohort of patients with grade 1 and 2 somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Methods: In this randomized, crossover, prospective, single-center, open-label phase 0 study, 8 patients received 1 GBq of [161Tb]Tb-DOTA-LM3 and 1 GBq of [177Lu]Lu-DOTATOC, with a 4-wk interval between injections. Quantitative SPECT/CT imaging was performed 3, 24, 72, and 168 h after administration of each radiopharmaceutical to calculate tumor and organ absorbed doses (3-dimensional dosimetry using a Monte Carlo-based ordered-subset expectation maximization algorithm). Results: After injection of 1 GBq of [161Tb]Tb-DOTA-LM3, SPECT/CT revealed excellent image quality with intense tumor uptake in all patients and a median of the mean effective tumor half-life of 103 h (range, 56-152 h) for [161Tb]Tb-DOTA-LM3 and 83 h (range, 30-122 h) for [177Lu]Lu-DOTATOC (P = 0.012). The medians of the mean tumor absorbed doses of [161Tb]Tb-DOTA-LM3 and [177Lu]Lu-DOTATOC were 36.6 Gy/GBq (range, 15-196 Gy/GBq) and 7.0 Gy/GBq (range, 2.4-14.2 Gy/GBq), respectively (P = 0.008). The median kidney and bone marrow absorbed doses were 2.4 Gy/GBq (range, 1.8-3.1 Gy/GBq) and 0.31 Gy/GBq (range, 0.24-0.48 Gy/GBq) for [161Tb]Tb-DOTA-LM3 and 0.6 Gy/GBq (range, 0.4-0.8 Gy/GBq) and 0.04 Gy/GBq (range, 0.03-0.06 Gy/GBq) for [177Lu]Lu-DOTATOC, respectively (both P = 0.008). According to Common Terminology Criteria for Adverse Events version 5.0, grade 1-3 treatment-emergent adverse events occurred in 6 of 8 patients after administration of 1 GBq of [161Tb]Tb-DOTA-LM3. Conclusion: [161Tb]Tb-DOTA-LM3 showed a 7.6-fold-higher median tumor absorbed dose than that of [177Lu]Lu-DOTATOC. The tumor-to-bone marrow absorbed dose ratio was in the same range for [161Tb]Tb-DOTA-LM3 as for [177Lu]Lu-DOTATOC. The administration of 1 GBq of [161Tb]Tb-DOTA-LM3 was safe for all patients, without relevant adverse events.

BACKGROUND:The most common cause of endogenous hyperinsulinemic hypoglycemia in neonates [congenital hyperinsulinemic hypoglycemia (CHH)] is different monogenic forms of gene mutations. About 50% of the mutations are known. We present a new mutation within the short-chain L-3-hydroxyacyl-CoA dehydrogenase (HADH) gene causing CHH in 2 related patients. METHODS:The course of 2 consanguineous patients with CHH are presented with a follow-up of >30 years. NextSeq 500 sequencing was performed and confined on known genes with autosomal recessive inheritance, namely ABCC8 (MANE Select: NM_00352.6), HADH (MANE Select: NM_005327.7), and KCNJ11 (MANE Select: NM_00525.4). Acylcarnitine profiles were measured and 68Ga-DOTA exendin positron emission tomography/computer tomography was performed. RESULTS:CHH was diagnosed in both patients in the neonatal period. A therapy with diazoxid was initiated, which initially stabilized the disease in both children. With advancing age, more hypoglycemic events occurred with an increase in carbohydrate intake, leading to obesity in both patients. In addition to diazoxide, somatostatin analogues were successfully added in adulthood. A genetic analysis documented a new homozygote mutation in the HADH gene (HADH-variant c.796G > T). An acylcarnitine profile showed an increased plasma butyryl-carnitine, consistent with a dysfunction of the HADH enzyme. 68Gallium-DOTA-exendin showed an increased uptake in the whole pancreas in both patients. CONCLUSION:Clinical presentation, biochemical workup, and therapeutical response to diazoxide and somatostatin analogues are consistent with previous reports of HADH mutations. The overexpression of glucagon-like peptide 1 receptors in this context warrants further research.

AIMS:Patients with type 2 diabetes mellitus (T2DM) are at high risk for coronary artery disease (CAD) related events and are often asymptomatic. The role of cardiac imaging in screening asymptomatic T2DM patients remains controversial, as existing studies are limited by short follow-up periods. Therefore, study aim was to provide long-term (10 years) outcome data of T2DM patients screened with cardiac imaging. METHODS AND RESULTS:A total of 400 asymptomatic high-risk T2DM patients without history of CAD underwent screening with Single Photon Emission Computed Tomography (SPECT). Abnormal SPECT was defined as Summed Stress Score ≥ 4 or Summed Difference Score ≥ 2. Patients were followed for all-cause mortality and major adverse cardiovascular events (MACE, cardiovascular mortality + myocardial infarction).The mean age was 63 ± 8 years; 69% were male. Diabetic end-organ damage was present in 87% of patients. Baseline SPECT was abnormal in 22% of patients. Median follow-up was 11.1 (8.8, 12.8) years. Abnormal SPECT was associated with higher all-cause mortality [hazard ratio (HR) 1.614, P = 0.029] and MACE (HR 2.024, P = 0.009). A normal SPECT was associated with a significantly better prognosis (all-cause mortality 1.9 vs. 3.1%/year, P = 0.016; MACE 1.2 vs. 2.3%/year, P = 0.010). In the small subgroup of patients with abnormal SPECT, the treatment strategy (revascularization vs. conservative) had no effect on event-free survival. CONCLUSION:A normal SPECT was associated with an excellent long-term prognosis in high-risk T2DM patients. Hence, SPECT could serve as a valuable tool for advanced risk stratification in this population.

OBJECTIVE:The 72 h fasting test, gold standard for diagnosing endogenous hyperinsulinemic hypoglycemia (EHH), is cumbersome and costly. We evaluated exenatide, a GLP-1 receptor agonist, as a faster, less burdensome alternative diagnostic tool. DESIGN AND METHODS:In this prospective, placebo-controlled, double-blind, randomized cross-over, proof-of-principle study, 10 μg intravenous exenatide was compared to placebo in 14 patients with confirmed EHH in a fasting test. Fourteen matched controls received 10 μg exenatide unblinded. Clinical monitoring and measurements of glucose, insulin, C-peptide, and proinsulin were performed for 4 h. Follow-up for EHH patients included imaging and histology. RESULTS:Exenatide induced diagnostic hypoglycemia in 6 of 14 EHH patients (42%) compared to none with placebo (P = .005). In patients with EHH, glucose nadir occurred earlier after exenatide (67 min [95% CI 50-142] vs 210 min [95% CI 174-219], P < .0001) and at lower glucose levels (2.68 mmol/L [95% CI 2.26-3.02] vs 3.2 mmol/L [95% CI 2.92-3.77], P < .0001) compared to placebo. Proinsulin levels 120 min post-exenatide were higher in patients with EHH [69 pmol/L (95% CI 3.8-232)] compared to controls [9 pmol/L (95% CI 4.5-16.9), P = .0001]. Compared to the fasting test, exenatide significantly shortened time to hypoglycemia (1.38 h [95% CI .67-2.99] vs 12 h [95% CI 1.44-36.1], P = .032). Exenatide was well tolerated and preferred by patients over the fasting test. CONCLUSIONS:Exenatide is a promising, faster, less cumbersome, and less expensive diagnostic tool for EHH compared to the fasting test. Larger trials are warranted to confirm its diagnostic utility. Trial Registration  ClinicalTrials.gov (NCT04909333).

e17063 Background: 177 Lu-PSMA-617 has been established as a radioligand therapy (RLT) for patients with metastatic castration-resistant prostate cancer (mCRPC), demonstrating improved overall survival (OS) compared to the standard of care and a more favorable toxicity profile than chemotherapy in previously conducted prospective studies. 177 Lu-PSMA-I&T has been used as an alternative radioligand, with assumed bioequivalence for RLT in mCRPC. However, no prospective data on its safety and efficacy are currently available. Methods: Prospective, multicenter Swiss registry study (EKNZ 2021-01271) involving mCRPC patients undergoing RLT with 177 Lu-PSMA-I&T. Safety was assessed through laboratory parameters and adverse events (AEs) graded per CTCAE v5.0, evaluated before each treatment cycle and at 12 weeks after therapy completion. Efficacy was measured by PSA changes (based on PCWG3 criteria and PSA 90 , defined as a 90% PSA reduction) and imaging responses, including SPECT/CT after each cycle and CT, MRI, or PSMA PET-CT at 8–12 weeks post-RLT, with follow-ups every 6 months or as clinically indicated. Descriptive and comparative statistics, along with multivariate and Kaplan-Meier analyses, were performed to evaluate therapy safety, response, progression-free survival, and overall survival. Results: A total of 333 consecutive mCRPC patients received a median of 4 cycles of 177 Lu-PSMA-I&T (range: 1–6 cycles) over a median duration of 5.6 months (range: 0.7–11.3 months), with a cumulative activity of 24 GBq (range: 7–48 GBq). Patient characteristics included Gleason score >8 (72%), metastases in lymph nodes (71%), bones (94%), and visceral organs (26%). Most patients had prior treatment with ARSi (88%) and taxane-based chemotherapy (87%). The median follow-up was 12 months. Therapy-related adverse events (AEs) of any grade were anemia (27%), leukopenia (15%), thrombopenia (22%), neutropenia (8%), and acute kidney injury (14%). Grade 3–4 AEs were observed in 8%, 2%, 3%, 0%, and 0% of patients, respectively. The best PSA response during RLT showed a partial response (PR) in 41% and stable disease (SD) in 27%, with PSA 90 achieved in 17%. At 12 weeks post-RLT, PSA responses included PR in 26% and SD in 11%. Median overall survival (OS) was 13 months (95% CI: 11.7–14.3), PSA progression-free survival (PFS) was 4.1 months (95% CI: 3.4–4.8), and imaging PFS was 6.5 months (95% CI: 5.4–7.6). Conclusions: The first prospective multicenter registry data demonstrated that 177 Lu-PSMA-I&T therapy is safe and effective in mCRPC. When comparing our real-world data to previously reported phase III studies, the toxicity profile appears similar to that of 177 Lu-PSMA-617, with comparable treatment efficacy. Clinical trial information: EKNZ 2021-01271 .

A high proportion of patients referred for coronary artery disease (CAD) testing with myocardial perfusion imaging (MPI) have normal test results. With decreasing prevalence of CAD and overestimation of pre-test probability (PTP) by existing models, normal tests results have continuously increased over time. This study aimed to evaluate temporal trends of normal scan results over 23 years in a large referral center in Switzerland. Data from all available MPI scans (Single Photon Emission Computed Tomography and Positron Emission Tomography) performed between 2000 and 2023 were extracted from the electronic medical record. An abnormal scan result was defined as Summed Stress Score (SSS) ≥4. PTP according to the 2019 ESC guidelines on chronic coronary syndromes was calculated. Temporal trends of Summed Rest Score (SRS), Summed Difference Score (SDS) and SSS were also analyzed. Overall, 45’113 patients were analyzed. The mean age was 66 ± 11 years, 35% were female. Typical and atypical angina were reported in 22% and 24%, respectively. Overall, MPI was abnormal in 44%. Small (SDS ≥2) and relevant (≥10% myocardium involved) ischemia was observed in 36% and 13%, respectively. The proportion of normal scan results increased from 53% in 2000 to 62% in 2023 (p < 0.001) (figure 1). SRS and SSS, but not SDS decreased over time (figure 2). In multivariate regression analysis, the year of exam was a significant predictor for normal MPI (OR 1.026 (95% CI 1.023-1.029), p < 0.001). PTP remained unchanged over time (20% in 2000 vs. 21% in 2023) (figure 1). The proportion of normal scan results significantly increased over 23 years, whereas PTP remained unchanged. To counter this trend and reduce unnecessary diagnostic tests, patient preselection must further be optimized.