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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. [ABSTRACT FROM AUTHOR]

Background: While Ga-PSMA PET-MRI might be superior to PET-CT with regard to soft tissue assessment in prostate cancer evaluation, it is also known to potentially introduce additional PET image artefacts. Therefore, the impact of PET acquisition duration and attenuation data on artefact occurrence, lesion detectability, and quantification was investigated. To this end, whole-body PET list mode data from 12 patients with prostate cancer were acquired 1 h after injection of 2 MBq/kg [Ga]HBED-CC-PSMA on a hybrid PET-MRI system. List mode data were further transformed into data sets representing 300, 180, 90, and 30 s acquisition duration per bed position. Standard attenuation and scatter corrections were performed based on MRI-derived attenuation maps, complemented by emission-based attenuation data in areas not covered by MRI. A total of 288 image data sets were reconstructed with varying acquisition durations for emission and attenuation data with and without scatter and prompt gamma correction, and further analysed regarding image quality and diagnostic performance. Results: Decreased PET acquisition durations resulted in a significantly increased incidence of halo artefacts around kidneys and bladder, decreased lesion detectability and lower SUV as well as markedly lower arm attenuation values: Halo artefacts were present in 5 out of 12 cases at 300-s duration, in 6 at 180 s, in 10 at 90 s, and in 11 cases at 30 s. Using attenuation data of the 300 s scans restored artefact occurrence to the original 300-s level. Prompt gamma correction only led to small improvements in terms of artefact occurrence and size. Of the 141 detected lesions in the 300-s images one lesion was not detected at 180 s, 28 at 90 s, and 64 at 30 s. Using the 300-s attenuation map decreased non-detectability of lesions to zero at 180 s, 9 at 90 s, and 52 at 30 s. Attenuation maps at 90 and 30 s demonstrated markedly lower mean arm attenuation values (0.002 cm) than those at 300 s (0.084 cm), and 180 s (0.062 cm). Conclusions: Short acquisition durations of less than 3 minutes per bed position result in unacceptable image artefacts and decreased diagnostic performance in current whole-body Ga-PSMA PET-MRI and should be avoided. Increased image noise and imperfections in generated attenuation maps were identified as a paramount cause for image degradation. [ABSTRACT FROM AUTHOR]

Background: Radioligand therapy (RLT) with Lu-DKFZ-617 PSMA (Lu-PSMA) (prostate-specific membrane antigen) is a novel targeted therapy of metastatic prostate cancer. We analysed retrospectively the early side effects and the response rate in the first patients, who received a therapy with Lu-PSMA in our departments. Methods: RLT was performed in ten hormone- and/or chemo-refractory patients with distant metastases and progressive disease (mean age 73.5 years). Ga-PSMA HBED-CC PET/CT was performed in all patients prior to RLT. The median PSA level prior to the therapy was 298.5 ng/ml (range 5-853 ng/ml). All patients received CBC, renal and liver function tests the day before and 2 days after application (mean administered activity 5.6 GBq, range 4.1-6.1 GBq), followed by further tests every 2 weeks. All patients were contacted by telephone every week regarding side effects or any positive and negative changes. Results: Eight weeks after the therapy, seven patients (70 %) experienced a PSA decline, of whom six experienced more than 30 % and five more than 50 %. Three patients showed a progressive disease according to the PSA increase. No patient experienced any side effects immediately after injection of Lu-PSMA. Relevant hematotoxicity (grade 3 or 4) occurred 7 weeks after the administration in just one patient. The same patient showed a leucopenia grade 2. Two patients showed a disturbance of only 1 hematologic cell line, whereas one patient showed a reduction of grades 1 and 2 in leucocytes and thrombocytes, respectively. Six patients did not show any hematotoxicity during the 8 weeks after therapy. There was no relevant nephrotoxicity (grade 3 or 4). Conclusions: Our initial results indicate that RLT with Lu-PSMA is safe and seems to have low early side-effect profile. A relevant PSA decline was detected in 70 % of patients. [ABSTRACT FROM AUTHOR]