[en] Evaluation of ${}^{90}$Y liver radioembolization post-treatment clinical data using a whole-body Biograph Vision Quadra PET/CT to investigate the potential of protocol optimization in terms of scan time and dosimetry. 17 patients with hepatocellular carcinoma with median (IQR) injected activity 2393 (1348-3298) MBq were included. Pre-treatment dosimetry plan was based on ${}^{99m}$Tc-MAA SPECT/CT with Simplicit90Y${}^{TM}$ and post-treatment validation with Quadra using Simplicit90Y${}^{TM}$ and HERMIA independently. Regarding the image analysis, mean and peak SNR, the coefficient of variation (COV) and lesion-to-background ratio (LBR) were evaluated. For the post-treatment dosimetry validation, the mean tumor, whole liver and lung absorbed dose evaluation was performed using Simplicit90Y and HERMES. Images were reconstructed with 20-, 15-, 10-, 5- and 1- min sinograms with 2, 4, 6 and 8 iterations. Wilcoxon signed rank test was used to show statistical significance (p < 0.05). There was no difference of statistical significance between 20- and 5- min reconstructed times for the peak SNR, COV and LBR. In addition, there was no difference of statistical significance between 20- and 1- min reconstructed times for all dosimetry metrics. Lung dosimetry showed consistently lower values than the expected. Tumor absorbed dose based on Simplicit90Y${}^{TM}$ was similar to the expected while HERMES consistently underestimated significantly the measured tumor absorbed dose. Finally, there was no difference of statistical significance between expected and measured tumor, whole liver and lung dose for all reconstruction times. In this study we evaluated, in terms of image quality and dosimetry, whole-body PET clinical images of patients after having been treated with ${}^{90}$Y microspheres radioembolization for liver cancer. Compared to the 20-min standard scan, the simulated 5-min reconstructed images provided equal image peak SNR and noise behavior, while performing also similarly for post-treatment dosimetry of tumor, whole liver and lung absorbed doses.

[en] Purpose: To evaluate the feasibility of minimally invasive magnetic resonance imaging (MRI)-guided free-hand aspiration of symptomatic nerve route compressing lumbosacral cysts in a 1.0-Tesla (T) open MRI system using a tailored interactive sequence. Materials and Methods: Eleven patients with MRI-evident symptomatic cysts in the lumbosacral region and possible nerve route compressing character were referred to a 1.0-T open MRI system. For MRI interventional cyst aspiration, an interactive sequence was used, allowing for near real-time position validation of the needle in any desired three-dimensional plane. Results: Seven of 11 cysts in the lumbosacral region were successfully aspirated (average 10.1 mm [SD ± 1.9]). After successful cyst aspiration, each patient reported speedy relief of initial symptoms. Average cyst size was 9.6 mm (±2.6 mm). Four cysts (8.8 ± 3.8 mm) could not be aspirated. Conclusion: Open MRI systems with tailored interactive sequences have great potential for cyst aspiration in the lumbosacral region. The authors perceive major advantages of the MR-guided cyst aspiration in its minimally invasive character compared to direct and open surgical options along with consecutive less trauma, less stress, and also less side-effects for the patient.

[en] The present study aims at evaluating the preclinical and the clinical performance of [${}^{68}$Ga]Ga-DATA${}^{5m}$.SA.FAPi, which has the advantage to be labeled with gallium-68 at room temperature. [${}^{68}$Ga]Ga-DATA${}^{5m}$.SA.FAPi was assessed in vitro on FAP-expressing stromal cells, followed by biodistribution and in vivo imaging on prostate and glioblastoma xenografts. Moreover, the clinical assessment of [${}^{68}$Ga]Ga-DATA${}^{5m}$.SA.FAPi was conducted on six patients with prostate cancer, aiming on investigating, biodistribution, biokinetics, and determining tumor uptake. [${}^{68}$Ga]Ga-DATA${}^{5m}$.SA.FAPi is quantitatively prepared in an instant kit-type version at room temperature. It demonstrated high stability in human serum, affinity for FAP in the low nanomolar range, and high internalization rate when associated with CAFs. Biodistribution and PET studies in prostate and glioblastoma xenografts revealed high and specific tumor uptake. Elimination of the radiotracer mainly occurred through the urinary tract. The clinical data are in accordance with the preclinical data concerning the organ receiving the highest absorbed dose (urinary bladder wall, heart wall, spleen, and kidneys). Different to the small-animal data, uptake of [${}^{68}$Ga]Ga-DATA${}^{5m}$.SA.FAPi in tumor lesions is rapid and stable and tumor-to-organ and tumor-to-blood uptake ratios are high. The radiochemical, preclinical, and clinical data obtained in this study strongly support further development of [${}^{68}$Ga]Ga-DATA${}^{5m}$.SA.FAPi as a diagnostic tool for FAP imaging.

[en] PSMA-617 is a small molecule targeting the prostate-specific membrane antigen (PSMA). In this work, we estimate the radiation dosimetry for this ligand labeled with the alpha-emitter ²¹³Bi. Three patients with metastatic prostate cancer underwent PET scans 0.1 h, 1 h, 2 h, 3 h, 4 h and 5 h after injection of ⁶⁸Ga-PSMA-617. Source organs were kidneys, liver, spleen, salivary glands, bladder, red marrow and representative tumor lesions. The imaging nuclide ⁶⁸Ga was extrapolated to the half-life of ²¹³Bi. The residence times of ²¹³Bi were forwarded to the instable daughter nuclides. OLINDA was used for dosimetry calculation. Results are discussed in comparison to literature data for ²²⁵Ac-PSMA-617. Assuming a relative biological effectiveness of 5 for alpha radiation, the dosimetry estimate revealed equivalent doses of mean 8.1 Sv_RBE5/GBq for salivary glands, 8.1 Sv_RBE5/GBq for kidneys and 0.52 Sv_RBE5/GBq for red marrow. Liver (1.2 Sv_RBE5/GBq), spleen (1.4 Sv_RBE5/GBq), bladder (0.28 Sv_RBE5/GBq) and other organs (0.26 Sv_RBE5/GBq) were not dose-limiting. The effective dose is 0.56 Sv_RBE5/GBq. Tumor lesions were in the range 3.2-9.0 Sv_RBE5/GBq (median 7.6 Sv_RBE5/GBq). Kidneys would limit the cumulative treatment activity to 3.7 GBq; red marrow might limit the maximum single fraction to 2 GBq. Despite promising results, the therapeutic index was inferior compared to ²²⁵Ac-PSMA-617. Dosimetry of ²¹³Bi-PSMA-617 is in a range traditionally considered reasonable for clinical application. Nevertheless, compared to ²²⁵Ac-PSMA-617, it suffers from higher perfusion-dependent off-target radiation and a longer biological half-life of PSMA-617 in dose-limiting organs than the physical half-life of ²¹³Bi, rendering this nuclide as a second choice radiolabel for targeted alpha therapy of prostate cancer. (orig.)

[en] Highlights: • Combined ion-beam radiotherapy for osteosarcoma is a novel local therapeutic approach • Despite unfavorable size/localization toxicity was moderate/local control promising • FDG PET might serve as a surrogate for grading histopathologic regression in future. To investigate the role of combined ion-beam radiotherapy (CIBRT) with protons and carbon ions in a multimodal treatment strategy of inoperable osteosarcoma; final analysis of a one-armed, single center phase I/II trial.

No abstract available

[en] The main side effect of prostate-specific membrane antigen targeting alpha therapy (PSMA TAT) is dry mouth syndrome. Inflammation of the salivary glands and consequent reduced salivary function have been reported in patients after radioiodine therapy. The beneficial effects of sialendoscopy on radiation-induced inflammation in tissue are well known. Thus sialendoscopy with dilatation, saline irrigation and steroid injections (prednisolone) was performed before and after ²²⁵Ac-PSMA-617 TAT to reduce inflammatory effects in the salivary glands and to improve or prevent xerostomia. Eleven men with metastatic castration-resistant prostate cancer (mean age 68.5 years, range 58-80 years) underwent sialendoscopy, dilatation, saline irrigation and steroid injection of both submandibular and both parotid glands before or after every cycle of ²²⁵Ac-PSMA-617 TAT. Sialendoscopy and steroid injection were performed by a senior ENT physician. Quality of life was evaluated using two health-related quality of life (HRQOL) questionnaires, the Xerostomia Questionnaire (XQ) and the Xerostomia Inventory (XI) before and 3 months after the intervention. In all 11 patients both parotid and both submandibular glands were affected by radiation sialadenitis and sialendoscopy was performed. The patients experienced no complications after sialendoscopy, and showed a significant improvement in HRQOL as measured using the XQ and XI. After sialendoscopy the XQ score decreased significantly from 77.7 ± 13.6 to 42.7 ± 14.8 (p = 0.003) and the XI score decreased from 44.5 ± 6.9 to 25.8 ± 12.8 (p = 0.003). Due to the limited number of patients we only report tendencies. Sialendoscopy with dilatation, saline irrigation and steroid injection had beneficial effects on salivary gland function and HRQOL in patients undergoing ²²⁵Ac-PSMA-617 RLT. However, even with sialadenoscopic support after multiple cycles of TAT, salivary gland function was reduced and xerostomia was present. Therefore, not only inflammation but also the direct effect of radiation is a putative cause of dry mouth. Further research is necessary to determine the main side effects of PSMA TAT. (orig.)

[en] The aim of this retrospective analysis is to estimate the most appropriate single cycle and cumulative doses of ${}^{225}$Ac-DOTATOC in patients treated for somatostatin-receptor-expressing cancers. ${}^{225}$Ac-DOTATOC was administered to thirty-nine patients with various somatostatin-receptor-positive tumors. Baseline and follow-up ${}^{68}$Ga-DOTATOC PET/CT, lab tests, and renal scintigraphy were obtained. Patients received long-term follow-up either at the local cancer center or in close collaboration with external oncologists. Acute and chronic hematological toxicity was evaluated quantitatively over time. Long-term follow-up of creatinine was used to approximate the annual loss of estimated GFR (eGFR). Dose-dependent acute hematological toxicity was seen at single doses above 40 MBq or repeated doses greater than approximately 20 MBq ${}^{225}$Ac-DOTATOC at 4 month intervals. Treatment-related kidney failure occurred in 2 patients after a delay of >4 years but was independent of administered radioactivity, and other clinical risk factors were important contributors to renal decline. In general, the annual decline of eGFR among patients did not follow a clear dose-effect relationship even in patients with previous $\mathrm{\beta <!--\; ??\; -->}$-therapy. An average eGFR-loss of 8.4ml/min (9.9%) per year was observed which is similar to the experience with $\mathrm{\beta <!--\; ??\; -->}$-therapy studies. Treatment activities of approx. 20 MBq per cycle (4 monthly repetition) and cumulative doses up to 60-80 MBq generally avoided both acute and chronic grade 3/4 hematotoxicity in patients with advanced stage malignancies. Chronic renal toxicity was observed at these doses, but pre-existing renal risk factors were important co-factors. These data represent a starting point for additional research to more precisely define safety thresholds of ${}^{225}$Ac-DOTATOC.

[en] Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement. The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [${}^{177}$Lu]Lu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6-20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of $\ge <!--\; ???\; -->$50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6-20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p < 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12 months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7 months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p < 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia. The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.