Dataset Information

Human biodistribution and dosimetry of [¹¹C]-UCB-J, a PET radiotracer for imaging synaptic density.

ABSTRACT:

Rationale

[¹¹C]-UCB-J is an emerging tool for the noninvasive measurement of synaptic vesicle density in vivo. Here, we report human biodistribution and dosimetry estimates derived from sequential whole-body PET using two versions of the OLINDA dosimetry program.

Methods

Sequential whole-body PET scans were performed in 3 healthy subjects for 2 h after injection of 254 ± 77 MBq [¹¹C]-UCB-J. Volumes of interest were drawn over relevant source organs to generate time-activity curves and calculate time-integrated activity coefficients, with effective dose coefficients calculated using OLINDA 2.1 and compared to values derived from OLINDA 1.1 and those recently reported in the literature.

Results

[¹¹C]-UCB-J administration was safe and showed mixed renal and hepatobiliary clearance, with largest organ absorbed dose coefficients for the urinary bladder wall and small intestine (21.7 and 23.5 μGy/MBq, respectively). The average (±SD) effective dose coefficient was 5.4 ± 0.7 and 5.1 ± 0.8 μSv/MBq for OLINDA versions 1.1 and 2.1 respectively. Doses were lower than previously reported in the literature using either software version.

Conclusions

A single IV administration of 370 MBq [¹¹C]-UCB-J corresponds to an effective dose of less than 2.0 mSv, enabling multiple PET examinations to be carried out in the same subject.

Trial registration

EudraCT number: 2016-001190-32. Registered 16 March 2016, no URL available for phase 1 trials.

SUBMITTER: Cawthorne C

PROVIDER: S-EPMC8065069 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAttempts to associate amyloid-β (Aβ) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aβ plaque burden is not well-correlated with indices of clinical severity or neurodegeneration-at least in the dementia stage-as deposition of Aβ reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aβ deposition and synaptic density in early AD using positron emission tomography (PET). We hypothesized that global Aβ deposition would be more strongly inversely associated with hippocampal synaptic density in participants with amnestic mild cognitive impairment (aMCI; a stage of continued Aβ accumulation) compared to those with dementia (a stage of relative Aβ plateau).MethodsWe measured SV2A binding ([11C]UCB-J) and Aβ deposition ([11C]PiB) in 14 participants with aMCI due to AD and 24 participants with mild AD dementia. Distribution volume ratios (DVR) with a cerebellar reference region were calculated for both tracers to investigate the association between global Aβ deposition and SV2A binding in hippocampus. Exploratory analyses examined correlations between both global and regional Aβ deposition and SV2A binding across a broad range of brain regions using both ROI- and surface-based approaches.ResultsWe observed a significant inverse association between global Aβ deposition and hippocampal SV2A binding in participants with aMCI (r = - 0.55, P = 0.04), but not mild dementia (r = 0.05, P = 0.82; difference statistically significant by Fisher z = - 1.80, P = 0.04). Exploratory analyses across other ROIs and whole brain analyses demonstrated no broad or consistent associations between global Aβ deposition and regional SV2A binding in either diagnostic group. ROI-based analyses of the association between regional Aβ deposition and SV2A binding also revealed no consistent pattern but suggested a "paradoxical" positive association between local Aβ deposition and SV2A binding in the hippocampus.ConclusionsOur findings lend support to a model in which fibrillar Aβ is still accumulating in the early stages of clinical disease but approaching a relative plateau, a point at which Aβ may uncouple from neurodegenerative processes including synaptic loss. Future research should investigate the relationship between Aβ deposition and synaptic loss in larger cohorts beginning preclinically and followed longitudinally in conjunction with other biomarkers.

Dataset Information

Human biodistribution and dosimetry of [¹¹C]-UCB-J, a PET radiotracer for imaging synaptic density.

Rationale

Methods

Results

Conclusions

Trial registration

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Human biodistribution and dosimetry of [11C]-UCB-J, a PET radiotracer for imaging synaptic density.

Rationale

Methods

Results

Conclusions

Trial registration

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Human biodistribution and dosimetry of [¹¹C]-UCB-J, a PET radiotracer for imaging synaptic density.