Ziel/Aim: Current clinical dosimetry focuses on activity uptake at millimeter scales, measurable by SPECT or PET imaging. However, understanding the heterogeneous uptake distribution at the cellular level and its effect on dosimetry is essential for assessing response to radionuclide therapy. This study investigated the prolonged uptake kinetics of 177Lu-PSMA-I&T and 177Lu-PSMA-617 in LNCaP cells to determine cellular absorbed doses and correlate them with treatment effects.

Ziel/Aim: Red marrow irradiation is a major concern for patients with mCRPC undergoing [177Lu]Lu-PSMA therapy and monitoring the red marrow absorbed dose is recommended to minimise side effects. The aim of this study was to develop an automated workflow for full image-based red marrow dosimetry.

Following maximal safe resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) injected into the resection cavity offers a promising strategy for improving local tumor. The NOA-22 study (NCT05533242) investigates the 6A10-Fab fragment targeting carboxyanhydrase XII, labelled with lutetium-177, in a prospective, single-armed, multicenter phase I study setting, following a modified 3 + 3-design. Malignant glioma (WHO grades 3 + 4) IV and III) after concomitant radio-chemotherapy and adjuvant standard chemotherapy with no or small residual disease are included. The injected activity is adapted to the volume of the resection cavity, resulting in a dose of 44Gy (cohort 1), 48Gy (cohort 2) and 52Gy (cohort 3). Primary study objective is to determine the maximum tolerated dose and safety of adjuvant radio-immunotherapy with lutetium-177 labeled 6A10-Fab fragments. Three patients with glioblastoma concluded the first study cohort. No toxicities beyond grade 2 (CTCAE Version 5) were noted. One patient presented with a symptomatic increase in focal contrast enhancement and perifocal edema that decreased after a course of steroid treatment, consistent with therapy-associated changes. Dosimetry did not reveal absorbed doses above upper dose limits for organs at risk. All patients remain clinically stable and without tumor progression. Intracavitary injection of Lutetium-177 labeled 6A10 Fab fragments appears to be feasible and safe. The study currently enrolls patients in a planned escalated dose scheme of 48 Gy cumulative dose in cohort 2.

Internal dosimetry supports safe and effective patient management during radionuclide therapy. Yet, it is associated with high clinical workload, costs, and patient burden, as patient scans at multiple time points (MTPs) must be acquired. Dosimetry based on imaging at a single time point (STP) has continuously gained popularity. However, MTP protocols, used as a reference to judge the validity of STP dosimetry, differ depending on local requirements and deviate from the unknown patient-specific ground truth pharmacokinetics. The aim of this study was to compare the error and optimum time point for different STP approaches using different reference MTP protocols. Methods: Whole-body SPECT/CT scans of 7 patients (7.4-8.9 GBq of [177Lu]Lu-PSMA-I&T) were scheduled at 24, 48, 72, and 168 h after injection. Sixty lesions, 14 kidneys, and 10 submandibular glands were delineated in the SPECT/CT data. Two curve models, that is, a mono- and a biexponential model, were fitted to the MTP data, in accordance with goodness-of-fit analysis (coefficients of variation, sum of squared errors). Three population-based STP approaches were compared: one method published by Hänscheid et al., one by Jackson et al., and one using population-based effective half-lives in the mono- or biexponential curve models. Percentage differences between STP and MTP dosimetry were evaluated. Results: Goodness-of-fit parameters show that a monoexponential function and a biexponential function with shared population-based parameters and physical tail are reasonable reference models. When comparing both reference models, we observed maximum differences of -44%, -19%, and -28% in the estimated absorbed doses for lesions, kidneys, and salivary glands, respectively. STP dosimetry with an average deviation of less than 10% from MTP dosimetry may be feasible; however, this deviation and the optimum imaging time point showed a dependence on the chosen reference protocol. Conclusion: STP dosimetry for [177Lu]Lu-PSMA therapy is promising to boost the integration of dosimetry into clinical routine. According to our patient cohort, 48 h after injection may be regarded as a compromise for STP dosimetry for lesions and at-risk organs. The results from this analysis show that a common gold standard for dosimetry is desirable to allow for reliable and comparable STP dosimetry.

Although 221Fr and 213Bi have sufficient gamma emission probabilities, quantitative SPECT after [225Ac]Ac-PSMA-I T therapy remains challenging due to low therapeutic activities. Furthermore, 221Fr and 213Bi may underlie a different pharmacokinetics due to alpha recoil. We conducted a quantitative SPECT study and a urine analysis to investigate the pharmacokinetics of 221Fr and 213Bi and the impact on image-based lesion and kidney dosimetry. Five patients (7.7 ± 0.2 MBq [225Ac]Ac-PSMA-I T) underwent an abdominal SPECT/CT (1 h) at 24 and 48 h (Siemens Symbia T2, high-energy collimator, 440 keV/218 keV (width 20 Sv_RBE=5 /MBq using 221Fr and 213Bi SPECT images, compared to 0.16 ± 0.05/0.18 ± 0.06 and 0.36 ± 0.1/0.38 ± 0.1 Sv_RBE=5 /MBq considering either the 221Fr or 213Bi SPECT. SPECT/CT imaging and urine analysis showed minor differences of up to 10

Purpose According to the World Health Organization classification for tumors of the central nervous system, mutation status of the isocitrate dehydrogenase ( IDH ) genes has become a major diagnostic discriminator for gliomas. Therefore, imaging-based prediction of IDH mutation status is of high interest for individual patient management. We compared and evaluated the diagnostic value of radiomics derived from dual positron emission tomography (PET) and magnetic resonance imaging (MRI) data to predict the IDH mutation status non-invasively. Methods Eighty-seven glioma patients at initial diagnosis who underwent PET targeting the translocator protein (TSPO) using [ 18 F]GE-180, dynamic amino acid PET using [ 18 F]FET, and T1-/T2-weighted MRI scans were examined. In addition to calculating tumor-to-background ratio (TBR) images for all modalities, parametric images quantifying dynamic [ 18 F]FET PET information were generated. Radiomic features were extracted from TBR and parametric images. The area under the receiver operating characteristic curve (AUC) was employed to assess the performance of logistic regression (LR) classifiers. To report robust estimates, nested cross-validation with five folds and 50 repeats was applied. Results TBR GE-180 features extracted from TSPO-positive volumes had the highest predictive power among TBR images (AUC 0.88, with age as co-factor 0.94). Dynamic [ 18 F]FET PET reached a similarly high performance (0.94, with age 0.96). The highest LR coefficients in multimodal analyses included TBR GE-180 features, parameters from kinetic and early static [ 18 F]FET PET images, age, and the features from TBR T2 images such as the kurtosis (0.97). Conclusion The findings suggest that incorporating TBR GE-180 features along with kinetic information from dynamic [ 18 F]FET PET, kurtosis from TBR T2 , and age can yield very high predictability of IDH mutation status, thus potentially improving early patient management.

Ziel/Aim Das Ziel der Studie war eine Abschätzung der Ausbeute an Doppelstrangbrüchen (DSB) und der relativen radiobiologischen Wirksamkeit (RBW) von Ac-225- und Lu-177-PSMA. Die initiale Schadensverteilung nach dem Zerfall des Radionuklids und der Restschaden nach der DNS-Reparatur wurden betrachtet.

Purpose Quantitative SPECT for patient-specific dosimetry is a valuable tool in the scope of radionuclide therapy, although its clinical application for 225 Ac-based treatments may be limited due to low therapeutic activities. Therefore, the aim of this study was to demonstrate the feasibility of clinical quantitative low-count SPECT imaging during [ 177 Lu]Lu-PSMA-I&T/[ 225 Ac]Ac-PSMA-I&T treatment. Methods Eight prostate cancer patients (1000 MBq/8 MBq [ 177 Lu]Lu-PSMA-I&T/[ 225 Ac]Ac-PSMA-I&T) received a single-bed quantitative 177 Lu/ 225 Ac SPECT/CT acquisition (1 h) at 24 h post treatment (high-energy collimator, 16 projections p. head à 3.5 min, 128 × 128 pixel). The gamma peak at 440 keV (width: 10%) of the progeny 213 Bi was imaged along with the peak at 208 keV (width: 15%) of 177 Lu. Quantification included CT-based attenuation and window-based scatter correction plus resolution modelling. Gaussian post-filtering with a full-width-half-maximum of 30 mm and 40–45 mm was employed to match the signal-to-noise ratio of 225 Ac and 177 Lu, respectively. Results Kidney ( r = 0.96, p < 0.01) and lesion ( r = 0.94, p < 0.01) SUV for [ 177 Lu]Lu-PSMA-I&T and [ 225 Ac]Ac-PSMA-I&T showed a strong and significant correlation. Kidney SUV were significantly higher ( p < 0.01) for [ 225 Ac]Ac-PSMA-I&T (2.5 ± 0.8 vs. 2.1 ± 0.9), while for [ 177 Lu]Lu-PSMA-I&T lesion SUV were significantly higher ( p = 0.03; 1.8 ± 1.1 vs. 2.1 ± 1.5). For absorbed dose estimates, significant differences regarding the kidneys remained, while no significant differences for lesion dosimetry were found. Conclusion Quantitative low-count SPECT imaging of the peak at 440 keV during [ 225 Ac]Ac-PSMA-I&T therapy is feasible. Multi-isotope imaging for [ 177 Lu]Lu-PSMA-I&T/[ 225 Ac]Ac-PSMA-I&T therapy indicates accumulation of free 213 Bi in the kidneys.

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 Gliome werden nach der neuen WHO-Klassifikation insbesondere anhand ihres IDH-Mutationsstatus klassifiziert. Um diesen nicht-invasiv zum Zeitpunkt der Erstdiagnose voraussagen zu können, wurde in dieser Studie erstmals der diagnostische Wert multimodaler Radiomics-Analysen (FET-PET, TSPO-PET und MRT) zur Identifizierung einer IDH-Mutation evaluiert.

Ziel/Aim Die Dosimetrie mittels SPECT/CT ist ein wichtiger Teil der 177Lu-PSMA-Therapie. Aktuell werden für die klinische Effizienz wiederholt Messprotokolle mit einem Messzeitpunkt (MZP) untersucht. In dieser Studie sollen verschiedene Dosimetrie-Ansätze mit einem MZP verglichen und der Einfluss des optimalen MZP in Abhängigkeit vom gewählten Referenzmodell untersucht werden.

Ziel/Aim Das Ziel der Studie war die Untersuchung der Pharmakokinetik von Bi-213 für die kombinierte Therapie mit Ac-225-PSMA und Lu-177-PSMA für Patienten mit metastasiertem Prostatakarzinom (mCRPC). Dafür wurden serielle quantitative SPECT Messungen und Harn-Analysen durchgeführt.

Purpose A reliable method for regional in vivo imaging of radiation-induced cellular damage would be of great importance for the detection of therapy-induced injury to healthy tissue and the choice of adequate treatment of radiation emergency patients in both civilian and military events. This study aimed to investigate in a mouse model if positron emission tomography (PET) imaging with proliferation and apoptosis markers is potentially suitable for this purpose. Methods Four groups, including twenty mice (wild-type C57BL/6) each, were whole-body irradiated with 0 Gy, 0.5 Gy, 1 Gy, and 3 Gy and examined by PET over a six-month period at defined time points. 3'-[ 18 F]fluoro-3'-deoxythymidine ([ 18 F]FLT) and 2-(5-[ 18 F]fluoropentyl)-2-methyl malonic acid ([ 18 F]ML-10) were used to visualise proliferation and apoptosis. Regional standard uptake values were compared with respect to irradiation dose over time. Histologic data and peripheral blood cell values were correlated with the PET results. Results The hematopoietic bone marrow showed a significantly increased [ 18 F]FLT signal at early time points after radiation exposure (day 3 and day 7). This correlated with blood parameters, especially leukocytes, and histological data. A significantly increased [ 18 F]FLT signal also occurred in the gastrointestinal tract and thymus at early time points. An increased [ 18 F]ML-10 signal related to irradiation doses was observed in the bone marrow on day 8, but there was a high variability of standard uptake values and no correlation with histological data. Conclusion [ 18 F]FLT showed potential to visualise the extent, regional distribution and recovery from radiation-induced cellular damage in the bone marrow, gastrointestinal tract and thymus. The potential of [ 18 F]FLT imaging to assess the extent of bone marrow affected by irradiation might be especially useful to predict the subsequent severity of hematopoietic impairment and to adapt the therapy of the bone marrow reserve. [ 18 F]ML-10 PET proved to be not sensitive enough for the reliable detection of radiation induced apoptosis.

Abstract Background 177Lu-PSMA therapy has been successfully used to prolong the survival of patients with metastatic castration-resistant prostate cancer. Patient-specific dosimetry based on serial quantitative SPECT/CT imaging can support the understanding of dose–effect relationships. However, multiple SPECT/CT measurements can be challenging for patients, which motivates the investigation of efficient sampling schedules and their impact on dosimetry. In this study, different time samplings with respect to the number and timing of SPECT/CT acquisitions with and without a late measurement were investigated. Materials and methods In total, 43 lesions and 10 kidneys of 5 patients receiving 177Lu-PSMA-I&T therapy were investigated. Whole-body SPECT/CT measurements were performed at 1, 2, 3 and 7 days post-injection. For both lesions (isocontour-based segmentation) and kidneys (CT-based segmentation), a reference model was employed including all four time points. To identify the best-matching fit function out of a pre-defined set of models, visual inspection, coefficients of variation and sum of squared errors were considered as goodness-of-fit criteria. Biologically effective doses (BEDs) calculated with different time samplings (days 1, 2, 3/1, 2, 7/1, 3, 7/2, 3, 7 and 1, 2/1, 3/1, 7) were compared to the reference. Results The best-fit function was found to be a mono-exponential model for lesions and a bi-exponential model with a population-based parameter and two free parameters for kidneys. The BEDs calculated with the time sampling 1, 3, 7 days showed the lowest deviations from the reference for lesions with 4 ± 5%. Without day 7, still 86% of all lesions showed deviations from the reference < 10%. The outlier deviations showed a positive correlation with the effective half-life of the respective lesions. For kidneys, including days 1, 2, 3 achieved the best results with 0 ± 1%. Generally, deviations for kidneys were found to be small for all time samplings (max. 13%). Conclusions For combined optimization of the SPECT/CT time sampling for kidney and lesion dosimetry during 177Lu-PSMA-I&T therapy, the sampling with days 1, 3, 7 showed the smallest deviation from the reference. Without a late acquisition, using the schedule with days 1, 2, 3 is likewise feasible.