[177Lu]Lu-PSMA-617 was approved after the VISION trial demonstrated significant benefit in metastatic castration-resistant prostate cancer (mCRPC). This study evaluated outcomes of [177Lu]Lu-PSMA-617 with or without concurrent Androgen Receptor Pathway Inhibitors (ARPI) in a real-world setting. We retrospectively analyzed electronic health records of mCRPC patients treated with [177Lu]Lu-PSMA-617 in routine clinical practice between June 2023 and August 2024. Primary endpoints were overall survival (OS) and PSA50 response; secondary endpoints included PSA-progression-free survival (PSA-PFS), radiographic PFS (rPFS), and percentage PSA change from baseline. Baseline characteristics were compared using Mann–Whitney U and chi-square tests. Survival outcomes were evaluated using Kaplan–Meier and Cox regression analyses. Among 108 patients, 65 received [177Lu]Lu-PSMA-617 monotherapy and 43 concurrent ARPI therapy. Baseline characteristics were generally well balanced, with slightly higher hemoglobin and a trend toward lower PSA in the ARPI group. No significant between-group differences were observed for median OS (12.7 vs. 13.5 months; p = 0.96), PSA50 response rate (51.2

Purpose [177Lu]Lu-PSMA-617 was approved after the VISION trial demonstrated significant benefit in metastatic castration-resistant prostate cancer (mCRPC). This study evaluated outcomes of [177Lu]Lu-PSMA-617 with or without concurrent Androgen Receptor Pathway Inhibitors (ARPI) in a real-world setting.Methods We retrospectively analyzed electronic health records of mCRPC patients treated with [177Lu]Lu-PSMA-617 in routine clinical practice between June 2023 and August 2024. Primary endpoints were overall survival (OS) and PSA50 response; secondary endpoints included PSA-progression-free survival (PSA-PFS), radiographic PFS (rPFS), and percentage PSA change from baseline. Baseline characteristics were compared using Mann-Whitney U and chi-square tests. Survival outcomes were evaluated using Kaplan-Meier and Cox regression analyses.Results Among 108 patients, 65 received [177Lu]Lu-PSMA-617 monotherapy and 43 concurrent ARPI therapy. Baseline characteristics were generally well balanced, with slightly higher hemoglobin and a trend toward lower PSA in the ARPI group. No significant between-group differences were observed for median OS (12.7 vs. 13.5 months; p = 0.96), PSA50 response rate (51.2% vs. 52.3%; p = 0.91), PSA-PFS (6.3 vs. 6.2 months; p = 0.54), or median PSA change from baseline (-39.0% vs. -43.1%; p = 0.24). A non-significant trend in rPFS favored the ARPI group (10.6 vs. 9.8 months; p = 0.057). On multivariable Cox regression, concurrent ARPI use was not independently associated with OS (adjusted HR 1.29; p = 0.33).Conclusion In this real-world cohort of ARPI- and taxane-pretreated mCRPC patients, concurrent ARPI use during [177Lu]Lu-PSMA-617 was not independently associated with improved clinical outcomes. These exploratory findings do not provide evidence to support routine continuation of ARPI beyond progression at the time of radioligand therapy initiation.

The study investigated routinely used radiopharmaceuticals containing lutetium-177 (177Lu), providing reference values for their effective half-life (T1/2,eff). So far, no guidelines regarding discharging this patients exist, are essential to ensure radiation protection of the public. This study contributes to the development of binding discharge criteria regarding 177Lu therapies. This retrospective multicenter study comprised eight nuclear medicine departments. Two commercially available products and two in-house preparations were considered. Radiation measurement methods, in terms of measuring device, setup, and time points were reported, as well as dose rate measurements for T1/2,eff calculation. The study includes 210 dose rate measurement sets with a mean administered activity of (7149 ± 522) MBq. When only measurements up to 48 h p.i. were taken into account the T1/2, eff were shorter (Pluvicto 1.30 d, Lutathera 1.40 d, ihPSMA 1.45 d, ihRRT 1.97 d) compared to 168 h (1.60 d, 1.89 d, 2.10 d, and 2.85 d, respectively). Differences were statistically significant for all compounds except Lutathera. The 90th percentile of the T1/2,eff observed in late measurements (Pluvicto 2.0 d, Lutathera 3.0 d, ihPSMA 3.5 d, ihRRT 4.0 d) can be considered conservative values for discharge calculations. The T1/2,eff of 177Lu is considerably shorter than its T1/2,phy, owing to the pharmacokinetics of the entire molecule. This highlights the need of considering biological clearance mechanisms into calculations of discharge times for patients treated with 177Lu. If direct measurements are not feasible in clinical routine, reference values support inpatient planning while ensuring radiation protection.

Purpose Before selective internal radiation therapy (SIRT), 99mTc macroaggregated albumin (MAA) particles are injected from the same catheter position(s) as a surrogate for later resin sphere distribution and to enable predictive dosimetry. Deviations in tumor segmentation affect predicted tumor and normal-liver absorbed doses and therefore prescribed activity. This study investigates the magnitude of interobserver variability in tumor segmentation for inexperienced and experienced observers when using biphasic contrast-enhanced CT as part of the 99mTc-MAA SPECT/CT imaging protocol and how it impacts the resulting tumor and normal-liver doses. Methods One inexperienced observer (performing two segmentations eight weeks apart) and one experienced observer used MIM SurePlan LiverY90 software to create tumor regions of interest (ROIs) from the SPECT/CT data of 19 patients. These three sets of ROIs were compared to the original clinical ROIs that had been defined similarly by another experienced physician together with a physicist. The Dice Similarity Coefficient (DSC) was calculated as a measure of tumor ROI overlap. Additionally, the resulting tumor and normal-liver dose differences using the partition model (assumed homogeneity within tumor and normal-liver compartments, doses represented by their mean values) between the three retrospectively determined sets of ROIs and the clinical ROIs were calculated and compared between inexperienced and experienced observers. Results DSC values between 0.73 and 0.75 were observed, indicating moderate to good agreement of segmentations, for inexperienced and experienced observers alike. Tumor dose differences were -3±13%, 2±10%, 2±10%; normal-liver dose differences were 9±16%, -9±14%, -4±14%, showing no relevant differences between inexperienced and experienced observers. Conclusion Significant interindividual variability in tumor segmentation and thus non-negligible deviations in tumor and normal-liver doses exist even with high-quality SPECT/CT imaging; however, for inexperienced and experienced observers alike. Hence, inexperienced observers with limited training can perform acceptably well. The magnitude of this variability should be considered when choosing injected activity based on predictive dosimetry, nevertheless.

Positron emission tomography (PET) using fibroblast activation protein inhibitors (FAPI) has emerged as a robust imaging tool for solid tumours. The novel ligand [68Ga]BED003 (formerly known as [68Ga]Ga-OncoFAP-DOTAGA) has demonstrated very high affinity for the fibroblast activation protein and favourable biodistribution. This study aimed to assess the in vivo distribution of [68Ga]BED003 across a spectrum of solid tumours as a potential prerequisite for radioligand therapy. In this retrospective analysis, [68Ga]BED003 PET/CT or PET/MRI of 157 patients with 19 different solid malignancies were retrospectively analysed. A spherical volume of interest (VOI) was placed over the primary tumour, the most intense lymph node and distant metastases that were evaluated as at least likely malignant in the written reports, and the maximum standardized uptake value (SUVmax) was derived. Liver and blood pool background mean SUV (SUVmean) were assessed using standardised VOIs. Tumour-to-background ratios (TBRmax) were calculated as the ratio of SUVmax to background SUVmean. SUVmax and TBRmax values of primary tumours, lymph node, and distant metastases were compared using Wilcoxon rank-sum and signed-rank tests, as appropriate. Overall, 115 primary tumours, 70 lymph node metastases, and 116 distant metastases were analysed, yielding median SUVmax of 16.6, 12.3, and 11.9, respectively. No significant difference in SUVmax or TBRmax were observed between lymph node and distant metastases (all P > 0.05). In contrast, primary tumours demonstrated significantly higher uptake than lymph node and distant metastases (all P < 0.001), except for liver TBRmax when comparing primary tumours with lymph node metastases (P > 0.05). Across all 301 lesions, the median SUVmax, liver TBRmax and blood pool TBRmax was 14.7 (range, 4.2–35.9), 21.6 (range, 4.2–62.8) and 11.1 (range, 3.0–33.4), respectively. The highest median SUVmax and TBRmax (both) in cohorts with > 5 lesions were found in medullary thyroid, oesophageal, ovarian, cervical, breast, colorectal, and hepatocellular cancers. [68Ga]BED003-PET demonstrated consistently high uptake across diverse solid malignancies, supporting its potential role as a tool for multi-cancer diagnostic imaging and patient selection for FAP-targeted radioligand therapy.

Positron-emission tomography combined with computed tomography (PET/CT) is the diagnostic standard for patients with Hodgkin’s lymphoma. Positron-emission tomography combined with magnetic resonance imaging (PET/MRI) is an alternative diagnostic modality that reduces radiation exposure to the patient. This study aims to evaluate the potential merits of PET/MRI compared to PET/CT for target delineation for radiotherapy of Hodgkin’s lymphoma. Five patients with newly diagnosed Hodgkin’s lymphoma underwent PET/CT imaging directly followed by PET/MRI imaging as part of initial staging. Both modalities were subsequently compared regarding each patient’s diagnosed involved nodal regions. Three of these patients received radiotherapy after the completion of chemotherapy. In the radiotherapy planning CT, different gross tumor volumes and clinical target volumes were contoured for both PET/CT and PET/MRI and quantitatively compared using the Dice coefficient. No differences regarding the diagnosed disease stage were observed. The delineated tumor and target volumes showed minor differences without clinical significance. Positron-emission tomography/MRI is a viable option to assure adequate staging and later target delineation in patients with Hodgkin’s lymphoma. Due to the reduction of radiation exposure compared to PET/CT, it might be the preferable option if readily available.

Zielsetzung Evaluation des Nutzens eines Radiomics-gestützten Modells zur Vorhersage des Therapieansprechens und Überlebens von Patienten mit kolorektalen Lebermetastasen, die mittels transarterieller Radioembolisation (TARE) behandelt wurden.

Abstract A 73-year-old man with metastatic pancreatic neuroendocrine tumor was evaluated with 68Ga-DOTATATE PET/CT for peptide receptor radionuclide therapy. Both PET-positive and negative lesions were seen in the liver, along with extrahepatic metastases. Histopathology was obtained from one of the PET-negative liver lesions to exclude secondary malignancy. Histology confirmed a well-differentiated (G2) metastasis of pNET with high somatostatin receptor expression. We initiated peptide receptor radionuclide therapy with close monitoring of the PET-negative liver metastases. We present a rare case, where posttherapeutic scintigraphy revealed vigorous uptake of 177Lu-DOTATATE even in the 68Ga-DOTATATE PET-negative liver metastases. Follow-up PET/CT showed a partial response to therapy.

Die transarterielle Radioembolisation (TARE) ist eine lokal ablative Therapieoption bei primären und sekundären Lebertumoren mit leberdominanter Erkrankung. Dieser Artikel gibt einen Überblick über die gängigsten Indikationen, die Patientenselektion, die Therapieplanung und -durchführung sowie die Nachsorge der Patienten. Der Fokus liegt auf Yttrium-90-beladenen Glas- und Harzmikrosphären, wobei weite Teile dieser Übersicht auch für Holmium-166 beladene Mikrosphären gelten.

The aim of this proof-of-principle study combining data analysis and computer simulation was to evaluate the robustness of apparent diffusion coefficient (ADC) values for lymph node classification in prostate cancer under conditions comparable to clinical practice. To assess differences in ADC and inter-rater variability, ADC values of 359 lymph nodes in 101 patients undergoing simultaneous prostate-specific membrane antigen (PSMA)-PET/MRI were retrospectively measured by two blinded readers and compared in a node-by-node analysis with respect to lymph node status. In addition, a phantom and 13 patients with 86 lymph nodes were prospectively measured on two different MRI scanners to analyze inter-scanner agreement. To estimate the diagnostic quality of the ADC in real-world application, a computer simulation was used to emulate the blurring caused by scanner and reader variability. To account for intra-individual correlation, the statistical analyses and simulations were based on linear mixed models. The mean ADC of lymph nodes showing PSMA signals in PET was markedly lower (0.77 × 10−3 mm2/s) compared to inconspicuous nodes (1.46 × 10−3 mm2/s, p < 0.001). High inter-reader agreement was observed for ADC measurements (ICC 0.93, 95

Abstract Background Following resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) with 177Lu-labeled 6A10-Fab fragments targeting tumor-associated carbonic anhydrase XII and injected into the resection cavity offers a novel and promising strategy for improved tumor control. Methods Three glioblastoma patients underwent tumor resection followed by standard radio- and chemotherapy. These patients with stable disease following completion of standard therapy underwent iRIT on compassionate grounds. After surgical implantation of a subcutaneous injection reservoir with a catheter into the resection cavity, a leakage test with [99mTc]Tc-DTPA was performed to rule out leakage into other cerebral compartments. IRIT comprised three consecutive applications over three months for each patient, with 25%, 50%, 25% of the total activity injected. A dosimetry protocol was included with blood sampling and SPECT/CT of the abdomen to calculate doses for the bone marrow and kidneys as potential organs at risk. Results All three patients presented without relevant leakage after application of [99mTc]Tc-DTPA. Two patients underwent three full cycles of iRIT (592 MBq and 1228 MBq total activity). One patient showed histologically proven tumor progression after the second cycle (526 MBq total activity). No relevant therapy-associated toxicities or adverse events were observed. Dosimetry did not reveal absorbed doses above upper dose limits for organs at risk. Conclusions In first individual cases, iRIT with [177Lu]Lu-6A10-Fab appears to be feasible and safe, without therapy-related side effects. A confirmatory multicenter phase-I-trial was recently opened and is currently recruiting.

Ziel/Aim Selective internal radiation therapy (SIRT) has an established use for the treatment of HCC and hepatic metastases of colorectal cancer (CRC). However, it is also used less frequently to treat hepatic metastases of other solid cancer types (non-CRC). The aim of this study was to evaluate the efficacy and outcome of SIRT-therapy for non-CRC metastases in comparison to CRC by combined PET/MRI.

Keywords PSMA - bone scan - Xofigo - prostate cancer - medullary metastases

Abstract Background Radio-immunotherapy (RIT) with Lu- 177 labeled 6A10-Fab fragments, targeting tumor-associated carbonic anhydrase XII (CA12) and applied directly into the resection cavity, offers a promising strategy to address hibernating tumor burden after resection and completion of adjuvant treatment for glioblastoma. We report on the first in human applications. METHODS Three patients underwent microsurgical resection of glioblastoma. After completion of adjuvant radio- and chemotherapy, RIT was offered in a compassionate use setting. After implantation of an injection reservoir into the tumor cavity, three consecutive doses of Lu-177 labeled 6A10 Fab fragments were administered over three months, corresponding to 25% - 50% - 25% of the total activity. The injected dose was adapted to the size of the resection cavity. Dosimetry was performed with planar whole-body scintigraphy and SPECT/CT 12h, 24h, 48h, 76h and 5-7 days after injection. RESULTS Patient 1 (IDH1-Mutation) received three doses of RIT (total of 592 MBq) with stable disease 12 months after therapy and 26 months after initial diagnosis. Patient 2(IDH-Wildtype) had histologically proven tumor progression after the second cycle (total of 526 MBq). Patient 3 (IDH-Wildtype) has so far received one cycle of RIT (327 MBq of a planned total of 1300 MBq). No toxicity according to CTCAE version 6.0 or other adverse events related to RIT were observed. Dosimetry did not reveal absorbed doses above the upper dose limits for organs at risk. Conclusions Intracavitary radioimmunotherapy with Lu-177 labeled 6A10-Fab fragments appears to be a safe maintenance therapy for glioblastoma patients, albeit only assessed in three compassionate use situations far. A multicenter confirmatory phase-I-trial will be was initiated in May 2022 (EudraCT-No: 2015-004417-25) to determine the maximum tolerated dose and safety of adjuvant RIT with Lu-177 labeled 6A10-Fab fragments.