The aim of this retrospective study was to identify pre-therapeutic predictive laboratory and molecular imaging biomarkers for response and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Pre-therapeutic laboratory and [⁶⁸Ga]Ga-PSMA-11 PET/CT data of n = 102 mCRPC patients receiving [¹⁷⁷Lu]Lu-PSMA-617 RLT within a prospective registry (REALITY Study, NCT04833517) were analyzed including laboratory parameters such as alkaline phosphatase (ALP), prostate-specific antigen (PSA), gamma glutamyl transferase (GGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), neuron specific enolase (NSE), hemoglobin (Hb), and imaging parameters such as maximum standardized uptake value of the tumor lesions (SUV_max), the mean standardized uptake value of all tumor lesions (SUV_mean), the whole-body molecular tumor volume (MTV), and the whole-body total lesion PSMA (TLP). Mann–Whitney U test, univariate and multivariable Cox-regression were performed to test for association of the parameters with response and OS. The SUV_mean of all lesions was significantly different between responders and non-responders (SUV_mean responders 8.95 ± 2.83 vs. non-responders 7.88 ± 4.46, p = 0.003), whereas all other tested biochemical and imaging parameters did not reveal significant differences. Hb and the molecular imaging parameters MTV and TLP showed a significant association with OS (p = 0.013, p = 0.005; p = 0.009) in univariant Cox regression; however, only TLP remained significant in multivariable analysis (Hazard ratio 1.033, p = 0.009). This study demonstrates a statistically significant association between the quantitative PET/CT imaging parameter SUV_mean and PSA response, as well as between the baseline TLP and OS of mCRPC patients undergoing RLT.

We report a [¹⁸F]fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) scan of a 17-year-old male presenting increased focal glucose metabolism of a histologically proven solitary nodular fasciitis mimicking an extranodal manifestation of Hodgkin lymphoma. This interesting image should draw attention to considering nodular fasciitis as a possible pitfall in the staging of malignant diseases.

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.

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.

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.

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.