Head to head comparison of two PET/CT imaging agents, [18F]D3FSP ([18F]P16-129) and [18F]AV45, in patients with alzheimer’s disease

Abstract Background A new β-amyloid (Aβ) targeting radiotracer, [18F]D3FSP ([18F]P16-129), for diagnosis of Alzheimer’s disease (AD) is reported. This radiotracer is a deuterated N-methyl derivative of Amyvid (AV-45, florbetapir f18) which was FDA-approved in 2013. Deuteration may alter a tracer’s P...

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Main Authors: David Alexoff, Dean F. Wong, Hiroto Kuwabara, Robert F. Dannals, Karl Ploessl, Hank F. Kung
Format: Article
Language:English
Published: SpringerOpen 2025-06-01
Series:EJNMMI Research
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Online Access:https://doi.org/10.1186/s13550-025-01276-w
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author David Alexoff
Dean F. Wong
Hiroto Kuwabara
Robert F. Dannals
Karl Ploessl
Hank F. Kung
author_facet David Alexoff
Dean F. Wong
Hiroto Kuwabara
Robert F. Dannals
Karl Ploessl
Hank F. Kung
author_sort David Alexoff
collection DOAJ
description Abstract Background A new β-amyloid (Aβ) targeting radiotracer, [18F]D3FSP ([18F]P16-129), for diagnosis of Alzheimer’s disease (AD) is reported. This radiotracer is a deuterated N-methyl derivative of Amyvid (AV-45, florbetapir f18) which was FDA-approved in 2013. Deuteration may alter a tracer’s PK such that imaging performance is improved. A head-to-head comparison between these two imaging agents was conducted in AD patients. A separate biodistribution study was conducted on six healthy subjects, and radiation dosimetry estimation was obtained. Results Eight patients, clinically diagnosed with Alzheimer’s disease, had an average age of 61.1 ± 10.0 years, and an average MMSE score of 21 ± 4. Each patient underwent paired 90-minute dynamic PET/CT scans separately within a few weeks (323 ± 31 MBq of [18F]D3FSP or [18F]AV45; florbetapir f18). SUVR (50–70 min) and Distribution Volume Ratio (DVR) of 43 brain regions were evaluated. The average SUVR across cortical gray matter was 1.65 ± 0.21 for [18F]AV45 and 1.65 ± 0.23 for [18F]D3FSP, while global DVRs were 1.36 ± 0.14 and 1.37 ± 0.13 for [18F]AV45 and [18F]D3FSP respectively. Strong correlations (R2 = 0.8–0.9) were observed between tracers for both SUVR and DVR, with slopes of ~ 0.9 (SUVR) and ~ 1 (DVR). No image artifacts or confounds influenced the visual interpretation of [18F]D3FSP compared to [18F]AV45. Conclusions Results showed no difference between [18F]D3FSP and [18F]AV45 and no benefit of deuteration at the N-methyl site. Even so, [18F]D3FSP may be a useful alternative for PET/CT imaging of Aβ deposits in the brain as its binding characteristics were very similar to its non-deuterated analog, the FDA-approved drug [18F]AV45. Trial registration Clinicaltrials.org, NCT03902548. Registered 01/07/2018.
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spelling doaj-art-c0253ae557cd4f2f8560e1787cd22c372025-08-20T03:31:42ZengSpringerOpenEJNMMI Research2191-219X2025-06-0115111010.1186/s13550-025-01276-wHead to head comparison of two PET/CT imaging agents, [18F]D3FSP ([18F]P16-129) and [18F]AV45, in patients with alzheimer’s diseaseDavid Alexoff0Dean F. Wong1Hiroto Kuwabara2Robert F. Dannals3Karl Ploessl4Hank F. Kung5Five Eleven Pharma IncDepartment of Radiology, Johns Hopkins University School of MedicineDepartment of Radiology, Johns Hopkins University School of MedicineDepartment of Radiology, Johns Hopkins University School of MedicineFive Eleven Pharma IncFive Eleven Pharma IncAbstract Background A new β-amyloid (Aβ) targeting radiotracer, [18F]D3FSP ([18F]P16-129), for diagnosis of Alzheimer’s disease (AD) is reported. This radiotracer is a deuterated N-methyl derivative of Amyvid (AV-45, florbetapir f18) which was FDA-approved in 2013. Deuteration may alter a tracer’s PK such that imaging performance is improved. A head-to-head comparison between these two imaging agents was conducted in AD patients. A separate biodistribution study was conducted on six healthy subjects, and radiation dosimetry estimation was obtained. Results Eight patients, clinically diagnosed with Alzheimer’s disease, had an average age of 61.1 ± 10.0 years, and an average MMSE score of 21 ± 4. Each patient underwent paired 90-minute dynamic PET/CT scans separately within a few weeks (323 ± 31 MBq of [18F]D3FSP or [18F]AV45; florbetapir f18). SUVR (50–70 min) and Distribution Volume Ratio (DVR) of 43 brain regions were evaluated. The average SUVR across cortical gray matter was 1.65 ± 0.21 for [18F]AV45 and 1.65 ± 0.23 for [18F]D3FSP, while global DVRs were 1.36 ± 0.14 and 1.37 ± 0.13 for [18F]AV45 and [18F]D3FSP respectively. Strong correlations (R2 = 0.8–0.9) were observed between tracers for both SUVR and DVR, with slopes of ~ 0.9 (SUVR) and ~ 1 (DVR). No image artifacts or confounds influenced the visual interpretation of [18F]D3FSP compared to [18F]AV45. Conclusions Results showed no difference between [18F]D3FSP and [18F]AV45 and no benefit of deuteration at the N-methyl site. Even so, [18F]D3FSP may be a useful alternative for PET/CT imaging of Aβ deposits in the brain as its binding characteristics were very similar to its non-deuterated analog, the FDA-approved drug [18F]AV45. Trial registration Clinicaltrials.org, NCT03902548. Registered 01/07/2018.https://doi.org/10.1186/s13550-025-01276-wBrainAlzheimer’s diseaseDiagnostic imaging and β-amyloid plaques
spellingShingle David Alexoff
Dean F. Wong
Hiroto Kuwabara
Robert F. Dannals
Karl Ploessl
Hank F. Kung
Head to head comparison of two PET/CT imaging agents, [18F]D3FSP ([18F]P16-129) and [18F]AV45, in patients with alzheimer’s disease
EJNMMI Research
Brain
Alzheimer’s disease
Diagnostic imaging and β-amyloid plaques
title Head to head comparison of two PET/CT imaging agents, [18F]D3FSP ([18F]P16-129) and [18F]AV45, in patients with alzheimer’s disease
title_full Head to head comparison of two PET/CT imaging agents, [18F]D3FSP ([18F]P16-129) and [18F]AV45, in patients with alzheimer’s disease
title_fullStr Head to head comparison of two PET/CT imaging agents, [18F]D3FSP ([18F]P16-129) and [18F]AV45, in patients with alzheimer’s disease
title_full_unstemmed Head to head comparison of two PET/CT imaging agents, [18F]D3FSP ([18F]P16-129) and [18F]AV45, in patients with alzheimer’s disease
title_short Head to head comparison of two PET/CT imaging agents, [18F]D3FSP ([18F]P16-129) and [18F]AV45, in patients with alzheimer’s disease
title_sort head to head comparison of two pet ct imaging agents 18f d3fsp 18f p16 129 and 18f av45 in patients with alzheimer s disease
topic Brain
Alzheimer’s disease
Diagnostic imaging and β-amyloid plaques
url https://doi.org/10.1186/s13550-025-01276-w
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