177Lu-PSMA radiopharmaceutical therapy shows favorable clinical responses for metastatic castration-resistant prostate cancer patients but may cause radiation-induced kidney damage due to specific and nonspecific activity accumulation. We evaluated the association between cumulative kidney absorbed doses and long-term kidney toxicity. This retrospective analysis included 127 patients who underwent treatment of mCRPC using 177Lu-based ligands (7.4 GBq at each cycle for [177Lu]Lu-PSMA-617 [n = 25] or 3.6–9.5 GBq throughout the treatment for [177Lu]Lu-PSMA-I T [n = 102]). MIM Software (7.3.4) was used to calculate the absorbed dose (AD) to the kidney (CT-based segmentation) using one of three validated protocols based on data availability: multiple timepoint acquisition, Hänscheid approach at 48 h, or the prior information approach. [99mTc]Tc-MAG3 scintigraphy scans were used to obtain tubular excretion rates, while serum-based sampling for glomerular filtration rate (eGFR) quantification was used. Up to 36 months post-treatment initiation CTCAE v5.0: Chronic Kidney Disease was determined. The AD of [177Lu]Lu-PSMA-617 (0.26 ± 0.09 Gy/GBq) was significantly less than [177Lu]Lu-PSMA-I T (0.32 ± 0.13 Gy/GBq) [p = 0.01] at cycle 1. Kidney AD per cycle did not significantly change across treatment cycles for either [177Lu]Lu-PSMA-617 (median change: cycle 1–2, 1
Background Poly (ADP-ribose) polymerase-1 (PARP1) inhibitors are used for treatment of advanced breast, ovarian, and prostate cancer with germline or somatic BRCA1/2 mutations. However, not all patients respond to these drugs, and therapy-predictive biomarkers are needed to optimise the benefit-risk balance. The 11C-labelled PARP1-selective radiopharmaceutical [11C]AZ14193391 has emerged as a promising radioligand to identify eligible patients. The aim of this study was to investigate the safety and to determine the biodistribution and dosimetry of [11C]AZ14193391. A secondary aim was to investigate the parametric bootstrap method to determine time-integrated activity coefficients (TIACs), absorbed doses, and effective dose.Results Ten participants (5 breast, 3 ovarian, 2 prostate cancer) were injected with 5.7 MBq/kg [11C]AZ14193391. Participants underwent five positron emission tomography (PET) acquisitions, ranging from the base of the skull to the proximal femur, at approximately 0, 10, 20, 30, and 45 min post-injection. Participants were monitored for changes in vital signs and were contacted 24 h after injection. No adverse events occurred. Visual evaluation of PET images showed high activity concentrations in the gastrointestinal tract, liver, kidneys, red marrow, pancreas, salivary glands, and spleen. Organs were segmented on a low-dose computed tomography image with an automatic segmentation tool (TotalSegmentator extension in 3D Slicer). The segmentations were reviewed and corrected based on the PET images. Time-activity curve (TAC) fits were determined with two TAC fit methods: 1) individual and 2) parametric bootstrap, to calculate TIACs. Absorbed doses and effective dose were determined with IDAC-Dose 2.1 from eleven source organs. Mean effective dose was estimated to be 5.0 (SD = 0.3) & micro;Sv/MBq with individual TAC fits and 5.0 (SE = 0.1) & micro;Sv/MBq with parametric bootstrap TAC fits. The organs receiving the highest mean absorbed doses per injected activity were liver, kidneys, and spleen. Gallbladder, red marrow, salivary glands, and spleen showed continued accumulation during the PET acquisitions.Conclusions Imaging with [11C]AZ14193391 is feasible and safe. Our results suggest that the radiation-induced risk is low, warranting further studies to evaluate the potential benefits of this diagnostic approach. The parametric bootstrap method estimated the population variability in the effective dose, but not in the TIACs.Clinical Trial Registry Ongoing recruitment Human Pharmacology (phase I) trial in Sweden including cancer patients in the age range (18-64) years. Sponsor: Karolinska University Hospital. : Registry identifier: EU CT 2022-502918-87-00; Date of registration: 2023-08-17.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly diagnosed using bone scintigraphy. Nuclear medicine (NM) physicians play a central role in the diagnosis of cardiac amyloidosis. The DIAM-ATTR national survey aimed to assess current practices and reporting patterns for diagnosing ATTR-CM among NM physicians in France. A cross-sectional online survey was distributed to all NM physicians in France between March and May 2024. The survey addressed scintigraphy acquisition protocols, radiotracer use, image interpretation, and reporting habits for suspected ATTR-CM. Among the 774 NM physicians invited, 100 completed the survey (12.9
Targeted radiotherapy (TRT) against Programmed death-ligand 1 (PD-L1) in triple-negative breast cancer (TNBC) has been relatively unexplored and is a biologically available and radiosensitive target. Here, we assess the efficacy and safety of a PD-L1 TRT and quantify tumor and organ-specific distributions for the treatment of TNBC. The PD-L1-targeting antibody atezolizumab was radiolabeled with lutetium-177. Athymic nude mice bearing high PD-L1 expressing MDA-MB-231 human TNBC tumors were treated with saline, 9.25 MBq, or 18.5 MBq of [177Lu]Lu-atezolizumab, and Single photon emission computed tomography (SPECT) imaging was acquired. Dosimetry to organs was quantified following biodistributions at multiple timepoints post injection. Tumor volumes and body weight were monitored for 60 days, and relevant organs were H E stained for pathological assessment. One- and two-way ANOVAs and log rank tests were utilized to assess differences between treatments. Both [177Lu]Lu-atezolizumab doses significantly reduced tumor volume compared to control by day 20 (18.5 MBq, p < 0.05) or day 24 (9.25 MBq, p < 0.05) post-treatment and increased median survival (35 versus 52 and 60 days in control, 9.25 MBq and 18.5 MBq treated mice, respectively, p < 0.01). As expected with antibody-based radiopharmaceuticals, the liver was the highest dosed organ following [177Lu]Lu-atezolizumab. No weight loss was observed in treated groups, and histology revealed minimal clearance organ toxicity. [177Lu]Lu-atezolizumab resulted in significantly decreased tumor volumes and increased survival in a mouse model of TNBC. This supports [177Lu]Lu-atezolizumab as a novel TRT which has the potential to improve immunotherapy outcomes in TNBC.
Patients with end-stage renal disease (ESRD) exhibit an elevated risk of cardiovascular events, with imaging-based risk stratification becoming increasingly important. This study compares the prognostic utility of [13N]NH3 PET/CT assessing myocardial blood flow (MBF), coronary flow reserve (CFR) and coronary artery calcium score (CACS) as well as 3D carotid ultrasound (for carotid plaque burden; cPB) in hemodialysis (HD) versus peritoneal dialysis (PD) patients listed for kidney transplantation. 41 ESRD patients (HD n = 31; PD n = 10; median follow-up 4.9 years) without known coronary artery disease underwent myocardial perfusion imaging with [13N]NH3 PET/CT, CACS, and 3D carotid ultrasound. HD patients exhibited lower myocardial stress blood flow (MBFstress) and CFR compared to PD patients (2.67 ± 0.67 vs. 2.97 ± 0.69; p = 0.24 and 2.5 ± 0.74 vs. 3.08 ± 1.12; p = 0.07). In the HD subgroup, only MBFstress correlated inversely with CACS and cPB (r = -0.32; p < 0.05 and r = -0.44; p < 0.05), whereas CFR did not (r=-0.14; p = 0.47 and r= -0.14; p = 0.44). On the other hand, both MBFstress and CFR were predictive of cardiovascular events in HD patients, although the number of events was low (n = 4). In contrast, PD patients exhibited only one single cardiovascular event in the follow-up and no significant imaging correlations were observed. MBFstress and CFR may emerge as prognostic markers for cardiovascular events in HD patients whereas their prognostic power in PD patients remains uncertain. HD patients show more pronounced impairment in MBFstress and atherosclerotic plaque burden in the carotid artery, highlighting particularly this parameter as a prognostic marker in this group.
