In vivo imaging of amyloid deposition in Alzheimer's disease using ¹⁸F-W372

Objective: To evaluate the effectiveness of a new tracer (7-methoxy-2-(6-¹⁸F-fluoropyridin-3-yl) imidazo [2, 1-β] -8-pyridinothiazole, ¹⁸F-W372 ) in distinguishing patients with AD from healthy controls (HC) by direct comparison with ¹⁸F-W372 and ¹¹C-Pittsburgh compound B (PIB). Methods: Paired ¹¹C-PIB and ¹⁸F-W372 scans were acquired in 8 patients with AD ((64.00±8.81) y, 1 male), 9HC ((64.78±4.02) y, 4 male) and 2 young volunteers. Dynamic PET scans were performed over a period of 40 min after injection of tracers. SUV and cortical-to-cerebellum SUV ratios (SUVR) were calculated. The median age and education across groups were compared using Kruskal-Wallis test. Wilcoxon rank-sum test was used to compare the mini-mental state examination (MMSE) scores between the HC and AD groups. Group differences of SUVR for ¹¹C-PIB and ¹⁸F-W372 were tested using a two-sample t-test. Results: Average MMSE scores were significantly lower in the AD patients than that in the HC (19.13±4.05 vs 28.89±0.78; T=36.00, P<0.01). The AD and HC were similar with respect to age and education (H=28.50 and 35.50, both P>0.05). The AD patients showed increased cortical ¹⁸F-W372 binding (e. g., the posterior and anterior cingulate), while the young volunteers demonstrated minimal cortical accumulation of the tracer. Although cortical-to-cerebellum SUVR of ¹⁸F-W372 in AD patients showed continual increase during the entire 40-min acquisition after injection, the separation between populations was not as robust as that of ¹¹C-PIB. Both tracers showed increased white-matter (WM) binding. The last 5-min phase (i. e. from 35 to 40 min) was taken as a representative sample for further analysis. In this period, the cortical-to-cerebellum SUVR of ¹¹C-PIB was significantly higher in AD patients than that in HC (1.48±0.22 vs 1.06±0.04; t=5.58, P<0.001). Similarly for ¹⁸F-W372, the average SUVR of AD patients was also significantly higher than that of HC (1.31±0.08 vs 1.17±0.06; t=3.78, P<0.01). Conclusions: ¹⁸F-W372 displayed similar affinity and distribution as ¹¹C-PIB. However, its target/nontarget distribution was not satisfactory. As a potential novel amyloid PET imaging agent; further research on ¹⁸F-W372 is warranted. (authors)