Imaging of neurodegenerative diseases using Tau PET/CT with [11C]PBB3 in a clinical setting

1463 Objectives: For many neurodegenerative diseases tau accumulation in the brain is a pathologic hallmark. Several new tau-specific radiotracers for positron emission tomography (PET) have been developed in the last few years, with [11C]PBB3 being one of the most promising compounds. In this study we retrospectively evaluated the first clinical experiences with PBB3 in a patient population with suspicion of neurodegenerative disease, mostly of the FTLD spectrum. Methods: 27 patients were examined with [11C]PBB3PET/CT. The standardized uptake value (SUV) - ratio of [11C]PBB3binding was determined for the individual lobes (frontal, temporal, parietal, occipital) and basal ganglia using cerebellar cortex as the reference. Correlations between SUVr and clinical tests (Mini-mental state examination - MMSE) and cerebrospinal fluid (CSF) parameters (CSF-Abeta; CSF-tau) were analyzed using the Pearson coefficient. [11C]PIB PET/CT was available for correlation in 14 cases and [18F]FDG PET/CT in 17 cases. Final diagnosis was established by integration of all clinical and imaging findings and follow up of the patients. Results: In 13 patients no or only faint uptake could be seen in [11C]PBB3 PET/CT (PBB3 negative) and moderate to pronounced uptake was noted in 14 patients (PBB3 positive). Concerning visual evaluation of the uptake patterns, PBB3 accumulation was most pronounced in the temporal lobe, followed by the occipital lobe, the frontal and parietal lobes. In addition, uptake was observed in the basal ganglia in all patients. Determination of the Pearson coefficient resulted in significant moderate correlations of SUVr for the respective lobes with MMSE (frontal: r = -0.538[asterisk]; occipital r = -0.457[asterisk]; parietal r = -0.574[asterisk][asterisk]) and CSF-tau (occipital r = -0.676[asterisk]) ([asterisk]p=0.05; [asterisk][asterisk]p=0.01). No correlation was observed concerning the basal ganglia. While all PBB3 negative scans were also PIB negative, PBB3 positive scans were either PIB positive or negative. Most PBB3 scans were FDG positive, with single FDG negative scans in both the PBB3 positive and negative group. Discussion: Uptake of [11C]PBB3was most pronounced in amyloid associated neurodegenerative diseases like suspected Alzheimer’s disease. In these cases [11C]PBB3PET/CT showed typical uptake patterns corresponding to areas of expected tau depositions in Braak stages III-VI. Moreover, [11C]PBB3uptake correlated significantly with MMSE and CSF-ABeta, thus suggesting that PBB3-PET may be a promising surrogate parameter for disease severity. However, due the generally only moderate intensity of [11C]PBB3uptake, the ultimate clinical impact on an individual patient level still has to be evaluated in larger prospective trials.