Accurately diagnosing Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) is challenging due to overlapping symptoms and limitations of current imaging methods. This study investigates the use of [11C]PBB3 PET/CT imaging to visualize tau pathology and improve diagnostic accuracy. Given diagnostic challenges with symptoms and conventional imaging, [11C]PBB3 PET/CT’s potential to enhance accuracy was investigated by correlating tau pathology with cerebrospinal fluid (CSF) biomarkers, positron emission tomography (PET), computed tomography (CT), amyloid-beta, and Mini-Mental State Examination (MMSE). We conducted [11C]PBB3 PET/CT imaging on 24 patients with suspected AD or FTLD, alongside [11C]PiB PET/CT (13 patients) and [18F]FDG PET/CT (15 patients). Visual and quantitative assessments of [11C]PBB3 uptake using standardized uptake value ratios (SUV-Rs) and correlation analyses with clinical assessments were performed. The scans revealed distinct tau accumulation patterns; 13 patients had no or faint uptake (PBB3-negative) and 11 had moderate to pronounced uptake (PBB3-positive). Significant inverse correlations were found between [11C]PBB3 SUV-Rs and MMSE scores, but not with CSF-tau or CSF-amyloid-beta levels. Here, we show that [11C]PBB3 PET/CT imaging can reveal distinct tau accumulation patterns and correlate these with cognitive impairment in neurodegenerative diseases. Our study demonstrates the potential of [11C]PBB3-PET imaging for visualizing tau pathology and assessing disease severity, offering a promising tool for enhancing diagnostic accuracy in AD and FTLD. Further research is essential to validate these findings and refine the use of tau-specific PET imaging in clinical practice, ultimately improving patient care and treatment outcomes.

Hybrid positron emission tomography/magnetic resonance imaging (PET/MR) opens new possibilities in multimodal multiparametric (m2p) image analyses. But even the simultaneous acquisition of positron emission tomography (PET) and magnetic resonance imaging (MRI) does not guarantee perfect voxel-by-voxel co-registration due to organs and distortions, especially in diffusion-weighted imaging (DWI), which would be, however, crucial to derive biologically meaningful information. Thus, our aim was to optimize fusion and voxel-wise analyses of DWI and standardized uptake values (SUVs) using a novel software for m2p analyses. Using research software, we evaluated the precision of image co-registration and voxel-wise analyses including the rigid and elastic 3D registration of DWI and [18F]-Fluorodeoxyglucose (FDG)-PET from an integrated PET/MR system. We analyzed DWI distortions with a volume-preserving constraint in three different 3D-printed phantom models. A total of 12 PET/MR-DWI clinical datasets (bronchial carcinoma patients) were referenced to the T1 weighted-DIXON sequence. Back mapping of scatterplots and voxel-wise registration was performed and compared to the non-optimized datasets. Fusion was rated using a 5-point Likert scale. Using the 3D-elastic co-registration algorithm, geometric shapes were restored in phantom measurements; the measured ADC values did not change significantly (F = 1.12, p = 0.34). Reader assessment showed a significant improvement in fusion precision for DWI and morphological landmarks in the 3D-registered datasets (4.3 ± 0.2 vs. 4.6 ± 0.2, p = 0.009). Most pronounced differences were noted for the chest wall (p = 0.006), tumor (p = 0.007), and skin contour (p = 0.014). Co-registration increased the number of plausible ADC and SUV combinations by 25%. The volume-preserving elastic 3D registration of DWI significantly improved the precision of fusion with anatomical sequences in phantom and clinical datasets. The research software allowed for a voxel-wise analysis and visualization of [18F]FDG-PET/MR data as a “combined diffusivity–metabolic index” (cDMI). The clinical value of the optimized PET/MR biomarker can thus be tested in future PET/MR studies.

Current aftercare after early breast cancer overlooks recent evidence on circulating free tumor DNA (ctDNA). In this case report, we present a patient with low-risk hormone-receptor-positive breast cancer. ctDNA was first detected using a tumor-informed approach 12 months after the initial diagnosis and remained positive throughout adjuvant therapy with letrozole, while routine staging examinations showed no signs of relapse. Clinical relapse was ultimately identified nearly six years after the initial diagnosis, resulting in a lead time of four years and nine months. Current studies on ctDNA in the adjuvant setting have been conducted in high-risk cohorts and have shown a median molecular lead time of 8.9–12.4 months. Our study supports the need for large randomized clinical trials involving low-risk breast cancer patients to drive changes in clinical practice.

Aim The aim of this study was to derive prognostic parameters from 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG-PET/CT) in patients with low-risk NSCLC and determine their prognostic value. Methods 81 (21 female, mean age 66 a) therapy-naive patients that underwent [18F]FDG-PET/CT before histologic confirmation of NSCLC with stadium I and II between 2008–2016 were included. A mean follow-up time of 58 months (13–176), overall and progression free survival (OS, PFS) were registered. A volume of interest for the primary tumor was defined on PET and CT images. Parameters SUV_max, PET-solidity, PET-circularity, and CT-volume were analyzed. To evaluate the prognostic value of each parameter for OS, a minimum p-value approach was used to define cutoff values, survival analysis, and log-rank tests were performed, including subgroup analysis for combinations of parameters. Results Mean OS was 58±28 months. Poor OS was associated with a tumor CT-volume >14.3 cm³ (p=0.02, HR=7.0, CI 2.7–17.7), higher SUV_max values >12.2 (p=0.003; HR=3.0, CI 1.3–6.7) and PET-solidity >0.919 (p=0.004; HR=3.0, CI 1.0–8.9). Combined parameter analysis revealed worse prognosis in larger volume/high SUV_max tumors compared to larger volume/lower SUV_max (p=0.028; HR=2.5, CI 1.1–5.5), high PET-solidity/low volume (p=0.01; HR=2.4, CI 0.8–6.6) and low SUV_max/high PET-solidity (p=0.02, HR=4.0, CI 0.8–19.0). Conclusion Even in this group of low-risk NSCLC patients, we identified a subgroup with a significantly worse prognosis by combining morphologic-metabolic biomarkers from [18F]FDG-PET/CT. The combination of SUV_max and CT-volume performed best. Based on these preliminary data, future prospective studies to validate this combined morphologic-metabolic imaging biomarker for potential therapeutic decisions seem promising. Received: 23 May 2023 Accepted after revision: 04 August 2023 Article published online: 11 September 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany