RT Journal Article SR Electronic T1 Comparison of [ 18F]D3FSP([18F]P16-129) and [18F] AV45 in Alzheimer’s Disease JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1457 OP 1457 VO 60 IS supplement 1 A1 Dean Wong A1 Hiroto Kuwabara A1 Kelly Kitzmiller A1 Ayon Nandi A1 Zabecca Brinson A1 Noble George A1 David Alexoff A1 James Brasic A1 Hong Fan A1 Daniel Holt A1 Lorena Gapasin A1 Josh Roberts A1 Wojciech Lesniak A1 Weiguo Ye A1 Yun Zhou A1 Robert Dannals A1 Hank Kung YR 2019 UL http://jnm.snmjournals.org/content/60/supplement_1/1457.abstract AB 1457Objectives: We have synthesized and studied the deuterated N-methyl derivative of Amyvid, [18F]D3FSP ([18F]P-16-129), in a pilot study in participants with Alzheimer’s disease (AD). AV-160, the major metabolite of florbetapir (Amyvid, AV45), is demethylated, with a lower affinity for beta amyloid plaques and the ability to cross the BBB. We hypothesized that [18F]D3FSP would have a higher binding affinity and slower peripheral in vivo metabolism, peripherally. This could improve image contrast or lower the required injected dose. Methods: We synthesized [18F]D3FSP at high specific activity (average 2164 ± 506 GBq/micromole). Six subjects with clinically diagnosed (AD, age, mean 60.2 ± 10.2 (SD), range 50-77 (4M), and average mean MMSE 21 ± 4 (SD, range 15-26), received paired 90-minute dynamic scans on a GE Advance PET of 333 ± 47 MBq of [18F]D3FSP and [18F]AV-45 (obtained commercially). Each venous samples for HPLC metabolite analysis were obtained at 5, 20, 45 and 90 minutes, post injection. The parent fraction and the desmethyl metabolites were identified from both [18F]D3FSP and [18F]AV45 scans employing HPLC radio-detection and uv detection by comparison with parent and desmethyl metabolite standards. Quantification included both SUVR (50-70 min) and DVR methods. Results: The DVR and SUVR of 43 brain regions, left and right merged, were obtained. The mean global SUVR across all cortical gray matter was 1.59 +/- 0.21 for [18F]AV45 and 1.61 +/- 0.25 for [18F]D3FSP (DVRs were 1.35 +/- 0.14 for AV45 and 1.37 +/- 0.16 for [18F]D3FSP). SUVR and DVR correlated strongly for both tracers (r > 0.9, p < 0.05). Also, there was close agreement in parent and desmethyl metabolite fractions. Overall, DVR and SUVR values across tracers were in very close agreement to each other (r > 0.96) and slope ̴ 1.0. Visual inspection of the AV45 scans met criteria for positivity by AVID established clinical review criteria, although 2 subjects were borderline. There was no evidence that image artifacts or confounds affected quantification of [18F]D3FSP compared to [18F]AV45. Anecdotally, visual review of the [18F]D3FSP and [18F]AV45 showed some moderate differences in image quality and loss of gray-white differentiation consistent with the quantification. Conclusions: In this small sample of 6 AD subjects, there were no substantial differences between [18F]D3FSP vs. [18F]AV45 but, 50% of the subjects did have slightly higher global cortical SUVR with [18F]D3FSP vs. [18F]AV45. Although all had a clinical diagnosis of AD, some of the subjects had only moderate quantitative uptake using the [18F]AV45 criteria. Visual inspection suggests [18F]D3FSP vs. [18F]AV45 may have some subtle differences in clinical readings and there may be quantitative differences in some individual cases but a larger population is needed with more severe patients before concluding the potential improved diagnostic value of [18F]D3FSP. Support by Five Eleven Pharma Inc.