Tau aggregates accumulate in the Alzheimer’s disease (AD) brain according to the established Braak staging scheme and spread from transentorhinal over limbic regions to the neocortex. To impact the management of AD patients, an in vivo tool for tau Braak staging is needed. First-generation tau tracers have limited performance in detecting early stages of tau. Therefore, we tested the corresponding capability of the next-generation tau tracer, ¹⁸F-PI-2620. We analyzed ¹⁸F-PI-2620 multicenter PET data from 37 beta-amyloid-positive AD dementia patients and those from 26 healthy controls. We applied kinetic modeling of the 0–60 min p.i. PET data using MRTM2 with the lower cerebellum as the reference region to extract Braak stage-dependent distribution volume ratios, whereas controls were used to define Braak stage PET positivity thresholds. Stage-dependent PET positivity widely followed the Braak scheme (except Braak stage III) presenting descending frequency of PET positivity from Braak I (43%), II (38%), III (49%), IV (35%), V (30%) to VI (14%). A strictly hierarchical model was met by 64% of AD dementia cases. Nineteen percent showed a hippocampal sparing tauopathy pattern. Thus, we could assign 87% to the six-stage hierarchical Braak model including tauopathy variants. ¹⁸F-PI-2620 PET appears to be able to perform Braak tau staging of AD in vivo.

Background: The gastrin-releasing peptide receptor (GRPr) is highly overexpressed in several solid tumors, including treatment-naïve and recurrent prostate cancer. [⁶⁸Ga]Ga-RM2 is a well-established radiotracer for PET imaging of GRPr, and [¹⁷⁷Lu]Lu-RM2 has been proposed as a therapeutic alternative for patients with heterogeneous and/or low expression of PSMA. In this study, we aimed to evaluate the expression of GRPr and PSMA in a group of patients diagnosed with castration-resistant prostate cancer (mCRPC) by means of PET imaging. Methods: Seventeen mCRPC patients referred for radio-ligand therapy (RLT) were enrolled and underwent [⁶⁸Ga]Ga-PSMA-11 and [⁶⁸Ga]Ga-RM2 PET/CT imaging, 8.8 ± 8.6 days apart, to compare the biodistribution of each tracer. Uptake in healthy organs and tumor lesions was assessed by SUV values, and tumor-to-background ratios were analyzed. Results: [⁶⁸Ga]Ga-PSMA-11 showed significantly higher uptake in tumor lesions in bone, lymph nodes, prostate, and soft tissues and detected 23% more lesions compared to [⁶⁸Ga]Ga-RM2. In 4/17 patients (23.5%), the biodistribution of both tracers was comparable. Conclusions: Our results show that in our cohort of mCRPC patients, PSMA expression was higher compared to GRPr. Nevertheless, RLT with [¹⁷⁷Lu]Lu-RM2 may be an alternative treatment option for selected patients or patients in earlier disease stages, such as biochemical recurrence.

Florbetaben (FBB) is a radiopharmaceutical approved by the FDA and EMA in 2014 for the positron emission tomography (PET) imaging of brain amyloid deposition in patients with cognitive impairment who are being evaluated for Alzheimer’s disease (AD) or other causes of cognitive decline. Initially, the clinical adoption of FBB PET faced significant barriers, including reimbursement challenges and uncertainties regarding its integration into diagnostic clinical practice. This review examines the progress made in overcoming these obstacles and describes the concurrent evolution of the diagnostic landscape. Advances in quantification methods have further strengthened the traditional visual assessment approach. Over the past decade, compelling evidence has emerged, demonstrating that amyloid PET has a strong impact on AD diagnosis, management, and outcomes across diverse clinical scenarios, even in the absence of amyloid-targeted therapies. Amyloid PET imaging has become essential in clinical trials and the application of new AD therapeutics, particularly for confirming eligibility criteria (i.e., the presence of amyloid plaques) and monitoring biological responses to amyloid-lowering therapies. Since its approval, FBB PET has transitioned from a purely diagnostic tool aimed primarily at excluding amyloid pathology to a critical component in AD drug development, and today, it is essential in the diagnostic workup and therapy management of approved AD treatments.

Ziel/Aim Progressive supranuclear palsy (PSP) is a primary 4R tauopathy. Post mortem studies identified six tau pathological stages. In PSP, tau aggregates start accumulating in the subthalamic nucleus (STN), with subsequent involvement of the globus pallidus (GP), striatum (ST), cerebellum with dentate nucleus (DN), frontal (FC) and occipital cortices (OC) [1]. We aimed to test whether this staging system is replicable by in vivo F-18-PI-2620 tau PET imaging. Methodik/Methods We analyzed data of 85 patients with the clinical diagnosis of PSP including 44 Richardson syndrome (RS)-PSP (19♀; age: 72±7yrs; PSPRS: 38±14; SEADL: 54±20; disease duration: 47±28months), 41 nonRS-PSP (17♀; age: 71±8yrs; PSPRS: 29±12; SEADL: 60±18; disease duration: 38±34months) patients and of 26 healthy controls (13♀; age: 67±11yrs). Dynamic F-18-PI-2620 PET imaging in a multicenter setting (sites in Germany, USA and Australia) was performed over 60min. After kinetic modeling (MRTM2, reference region=lower cerebellum), parametric distribution volume ratio images were analyzed and classified into six PSP stages according to the above hierarchical scheme [1]. The data of the controls defined the normal range (mean+2.5 SD) for each tau-in-PSP VOI. Ergebnisse/Results Tau-in-PSP VOI positivity varied regionally with 16% for STN, 18% for GP, 33% for ST, 19% for DN, 1% for FC and 5% for OC. 64% of RS-PSP patients were PET-positive, with 41% hierarchically staged as stage 1, 16% as stage 2, and 7% as stage 3. In the nonRS-PSP group, the frequencies were lower (46%, 36%, 5%, and 5%, respectively). In nonRS-PSP patients we found a correlation between highest PSP stage and age (r=0.37, p=0.02). In vivo tau PET staging was not associated with scores of clinical disease duration (PSPRS, SEADL or disease duration). Schlussfolgerungen/Conclusions In conclusion, F-18-PI-2620 PET seems to be able to perform in vivo PSP tau staging in vivo. Our data, however, challenge the concept of only one hierarchical system. More data are necessary to also elucidate the relation between the F-18-PI-2620 PET signal and the severity of the clinical phenotype. Publication Date: 14 April 2022 (online) © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany