Direct Comparison of [18F]FC119S and [11C]PiB of PET in Alzheimer's Disease, Mild Cognitive Impairment and Healthy Control Groups; an Open-label, Single-dose, Parallel, Evaluator-blind, Investigator Clinical Trial

19 Objectives The newly developed 18F-labeled amyloid tracer, [18F]FC119S, was recently introduced by FutureChem in South Korea. In this study, the depositions and retentions of amyloid plaques, measured by positron emission tomography (PET) with both [11C]PiB and [18F]FC119S, were compared prospectively in Alzheimer9s disease (AD), mild cognitive impairment (MCI) and healthy control (HC) groups. Methods Twenty eight HC and clinically diagnosed ten MCI, ten AD subjects were prospectively included. All subjects underwent [11C]PiB, [18F]FC119S PET/CT and MRI within four or less weeks interval. Tracer uptakes in cerebral gray matter and white matter were visually assessed by 3 independent nuclear medicine physicians. Any gray matter lesion that equal or more intense tracer uptake than white matter was considered as positive. Four cortical regions (frontal, parietal, temporal, occipital lobes) and reference regions (white matter, cerebellum) were evaluated. Standardized Uptake Value Ratio (SUVR) was measured and compared. MRI was visually assessed with Medial Temporal Lobe Atrophy (MTA) score. All adverse effects (AE) and serious adverse effects (SAE) during the clinical trial periods were collected with guidelines provided by Korea Food & Drug Administration (K-FDA). Results In HC group, all 28 subjects were scan negative for both tracers. In MCI and AD groups, 11 out of 20 subjects were [11C]PiB positive (MCI : 4/10, AD : 7/10) and 10 out of 20 subjects were [18F]FC119S positive (MCI : 4/10, AD : 6/10). [18F]FC119S PET showed more focal and nodular patterns of uptakes, whereas [11C]PIB PET did not. By region based analysis, 36 out of 80 areas were [11C]PiB positive (MCI : 13/40, AD : 23/40) and 34 out of 80 areas were [18F]FC119S positive (MCI : 14/40, AD : 20/40). Each pair of radiotracer uptakes in cerebral gray matters was strongly correlated regardless of tracer types. In MCI and AD groups, the concordance rate between two tracers was 95% (19/20) on patient based analysis and 90% (72/80) on region based analysis. With including HC group, it was 98% (47/48) and 96% (184/192) respectively. The SUVR of HC subjects were 1.03±0.05 in [11C]PiB and 1.09±0.06 in [18F]FC119S scan. The SUVR of MCI and AD subjects were 1.34±0.33, 1.45±0.36 in [11C]PiB and 1.32±0.18, 1.37±0.26 in [18F]FC119S scan, respectively. All HC subjects were MTA score 0. In MCI group, there were 3 subjects with MTA score 1, 6 subjects with MTA score 2, and 1 subject with MTA score 3. In AD group, there were 1 subject with MTA score 1, 6 subjects with MTA score 2, and 3 subjects with MTA score 3. There were no clinically significant AE or SAE for any subjects during the clinical trial periods. Conclusions The uptake patterns between tracers were slightly different, however, they did not affect the diagnostic accuracy significantly. One of possible reasons of these differences might be degree of disease progress or pathologic changes, and further studies are recommended. The SUVR and positivity of both tracers was highly concordant on patient based and region based analysis. Therefore, the new 18F-labeled amyloid tracers, [18F]FC119S, can be used to assess the amyloid plaques of brain with reliably high safety and accuracy.