We present a case of a 60-year-old woman diagnosed with metastasized small bowl NET G3 with high hepatic tumor burden and highly glucometabolic (FDG-avid) disease. In the postchemotherapy setting with progressive disease, the patient underwent PRRT with ¹⁷⁷Lu-DOTA-octreotate and ²²⁵Ac-DOTA-octreotate initially resulting in stable disease. In a novel approach, ²²⁵Ac-DOTA-LM3 (somatostatin receptor antagonist) was administered, leading to a favorable treatment response in the ¹⁸F-FDG PET/CT scan. This interesting image illustrates the promising antitumor potential of alpha-sst2 antagonist PRRT with ²²⁵Ac-DOTA-LM3, and to the best of our knowledge, it is the first documented evidence of superiority over standard alpha-PRRT from intraindividual comparison.

Aim: The heterogeneous expression of somatostatin receptors in gastroenteropancreatic neuroendocrine tumors (GEP-NET) leads to significant intra-individual variability in tracer uptake during pre-therapeutic [⁶⁸Ga]Ga-DOTATOC PET/CT for patients receiving peptide receptor radionuclide therapy (PRRT). This study aims to evaluate the lesion-based relationship between receptor-mediated tracer uptake and the functional response to PRRT.Methods: A retrospective analysis was conducted on 32 patients with metastatic GEP-NET (12 pancreatic and 20 non-pancreatic), all treated with [¹⁷⁷Lu]Lu-octreotate (4 cycles, with a mean of 7.9 GBq per cycle). [⁶⁸Ga]Ga-DOTATOC PET/CT was performed at baseline and 3 months after the final PRRT cycle. Tumor uptake was quantified using the standardized uptake value (SUV). For each patient, 2 to 3 well-delineated tumor lesions were selected as target lesions. SUV_max, SUV_mean (automated segmentation with a 50% SUV_max threshold), and corresponding tumor-to-liver ratios (SUV_maxT/L and SUV_meanT/L) were calculated. Functional tumor response was assessed based on the relative change in metabolic tumor volume (%ΔTV_PET). The correlation between baseline SUV parameters and lesion-based functional response was analyzed using Spearman’s rank correlation.Results: A total of 71 lesions were included in the analysis. The mean baseline SUV_max and SUV_mean were 28.1 ± 15.9 and 13.6 ± 5.1, respectively. Three months after PRRT completion, the mean %ΔTV_PET was 39.6 ± 52.1%. Baseline SUV_max and SUV_mean demonstrated a poor correlation with lesion-based response (p = 0.706 and p = 0.071, respectively). In contrast, SUV_maxT/L and SUV_meanT/L were significantly correlated with lesion-based response (SUV_meanT/L: p = 0.011, r = 0.412; SUV_maxT/L: p = 0.004, r = 0.434). Among patient characteristics—including primary tumor origin, baseline tumor volume, and metastatic sites—only pancreatic origin was significantly associated with functional tumor volume reduction (ΔTV_PET%: 56.8 ± 39.8 in pancreatic vs. 28.4 ± 50.1 in non-pancreatic NET; p = 0.020).Conclusion: The lesion-based molecular response to PRRT correlates with pretreatment somatostatin receptor PET uptake, particularly when expressed as tumor-to-liver SUV ratios (SUV_maxT/L and SUV_meanT/L).

Introduction: To enhance the effectiveness of radioligand therapy (RLT), new prostate-specific membrane antigen (PSMA) targeting radiopharmaceuticals utilizing alternative radionuclides are under active investigation. One promising alternative to the established ¹⁷⁷ Lu is the use of ¹⁶¹ Tb. A key advantage of ¹⁶¹ Tb is its emission of a higher proportion of low-energy conversion and Auger electrons, which may contribute to enhanced therapeutic effectiveness. This study provides a first exploratory evaluation of the efficacy and safety of [ ¹⁶¹ Tb]Tb-PSMA-617 in patients with progression after [ ¹⁷⁷ Lu]Lu-PSMA-617, aiming to generate early clinical insights. Methods: The study included 15 patients with mCRPC, who were enrolled in the “prospective registry to assess outcome and toxicity of targeted radionuclide therapy in patients with mCRPC in clinical routine“ (REALITY Study; NCT04833517). All patients had received conventional PSMA RLT using [ ¹⁷⁷ Lu]Lu-PSMA-617, which resulted in initial biochemical response (PSA decline ≥50%), followed by a biochemical relapse, prompting the re-initiation of PSMA RLT using [ ¹⁶¹ Tb]Tb-PSMA-617. Patients received a median of 3 (range: 2–7) cycles with mean administered activity of 5.4 ± 1.1 GBq and mean cumulative activity of 19.2 ± 6.4 GBq [ ¹⁶¹ Tb]Tb-PSMA-617. Treatment response was assessed both biochemically by serum PSA levels and through molecular imaging by total lesion PSMA (TLP) on [ ⁶⁸ Ga]Ga-PSMA-11 PET/CT scans. Adverse events were assessed at baseline and follow-up using the “Common Terminology Criteria for Adverse Events“ (Version 5.0). Results: [ ¹⁶¹ Tb]Tb-PSMA-617 RLT showed response rates of 66.7% (10/15 patients) based on biochemical assessment and 86.7% (13/15 patients) based on molecular imaging assessment. Beginning with the initiation of [ ¹⁶¹ Tb]Tb-PSMA-617 RLT, the median progression-free survival (PFS) was 6.4 months, and the median overall survival (OS) was 15.5 months. In total, 6 CTCAE grade deteriorations from grade 2 to grade 3 or from grade 3 to grade 4 were observed. No discontinuation of PSMA RLT due to adverse events was reported. Conclusions: [ ¹⁶¹ Tb]Tb-PSMA-617 RLT emerges as a promising treatment option, demonstrating encouraging response rates, preliminary clinical outcomes, and a favorable safety profile as second-line RLT in progressing patients who previously benefited from [ ¹⁷⁷ Lu]Lu-PSMA-617 RLT.

Background/Objectives: The augmentation of [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy by alpha emitting [²²⁵Ac]Ac-PSMA-617, known as the tandem therapy concept, is a promising escalating treatment option in advanced mCRPC. In this study, we evaluated the value of [¹⁸F]FDG PET/CT-derived molecular imaging biomarkers for predicting response and outcome to PSMA tandem RLT in n = 33 patients with insufficient response on [¹⁷⁷Lu]Lu-PSMA-617 monotherapy. Methods: Six different molecular imaging parameters at baseline, i.e., before initiation of PSMA tandem RLT with respect to SUV_max, SUV_peak, SUV₅, SUV_mean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were tested for association with response and overall survival (OS). Results: After the initiation of augmentation, 24.2% of patients with a previously insufficient response experienced partial remission, and 39.4% experienced stable disease. The median OS was 7 months (95% CI: 4–11 months). None of the tested parameters were able to predict the response (all p > 0.529). In contrast, the [¹⁸F]FDG PET/CT-derived whole-body molecular imaging parameter TLG was significantly (p = 0.029) associated with OS of patients undergoing [²²⁵Ac]Ac-PSMA-617 augmented [¹⁷⁷Lu]Lu-PSMA-617 RLT after insufficient response to [¹⁷⁷Lu]Lu-PSMA-617 monotherapy. Conclusion: Implementing [¹⁸F]FDG PET/CT in the management of PSMA-RLT in clinical practice may contribute to outcome prediction and provide a route to more individualized management in mCRPC.

We report a case of a 79-year-old male patient with a history of radical prostatectomy for prostate cancer. The patient presented with biochemical reoccurrence; however, previous conventional PSMA PET/CT using [¹⁸F]PSMA-1007 showed two indetermined findings with low uptake in the right iliac lymph nodes. Further MRI evaluation provided no additional information. A recently introduced PSMA tracer, [⁸⁹Zr]Zr-PSMA-617 (half-life: 3.3 days), was administered in an attempt to confirm the diagnosis and aid in potential radiation planning. [⁸⁹Zr]Zr-PSMA-617 PET/CT clearly revealed the previously indetermined right iliac lymph nodes as definitely metastatic and also identified additional lymph node metastases that were undetected in prior scans. This case highlights the potential superior sensitivity of [⁸⁹Zr]Zr-PSMA-617 PET/CT in detecting recurrent disease, especially in unclear settings of [¹⁸F]PSMA-1007 PET/CT and demonstrates its potential for guiding targeted radiation therapy with curative intent.

Large language models (LLMs) are increasingly explored for clinical use. However, the extent to which such models can reliably support physicians in reporting, staging, and the assessment of classification remains an active area of research. This study aimed to evaluate and compare multiple LLMs for automated PROMISE V2 classification for prostate cancer. A total of 126 unambiguous German-language PSMA PET/CT text reports were retrospectively analyzed, with reference standards established by expert consensus based on image interpretation and the original report text. Five LLMs (GPT-5.4, DeepSeek-V3.2, Claude Sonnet 4.6, Gemini 3 Flash and Grok 4) were assessed using two English-language prompting strategies of varying complexity. Agreement with the reference standard served as the primary endpoint. Performance varied in the short-prompt setting (36.5–79.4%) but improved consistently with the long prompt (74.6–86.5%), with Gemini 3 Flash achieving the highest agreement. Across PROMISE V2 subcategories, agreement rates were high (miT: 81.0–92.1%, miN: 92.9–96.0%, miM: 92.9–95.2%), despite inter-model differences. In conclusion, contemporary LLMs demonstrate promising performance in deriving PROMISE V2 scores from unambiguous original report texts, particularly when guided by detailed prompts.