Dataset Information

Radiation Dosimetry of a Novel Adenosine A_2A Receptor Radioligand [¹¹C]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats.

ABSTRACT:

Purpose

[¹¹C]Preladenant was developed as a novel adenosine A_2A receptor PET radioligand. The aim of this study was to determine the radiation dosimetry of [¹¹C]preladenant and to investigate whether dosimetry estimation based on organ harvesting can be replaced by positron emission tomography (PET)/x-ray computed tomography (CT) imaging in rats.

Procedures

Male Wistar rats (n?=?35) were i.v. injected with [¹¹C]preladenant. The tracer biodistribution was determined by organ harvesting at 1, 5, 15, 30, 60, and 90 min post injection. Hollow organs including the stomach, intestines, and urinary bladder were harvested with contents. In 10 rats, a 90-min dynamic PET/CT scan of the torso was acquired. Twenty volumes of interest (VOIs) were manually drawn on the PET image using the CT image of the same animal as anatomical reference. The dynamic time-activity curves were used to calculate organ residence times (RTs). Human radiation dosimetry estimates, derived from rat data, were calculated with OLINDA/EXM 1.1.

Results

PET-imaging and organ-harvesting estimated comparable organ RTs, with differences of 6-27 %, except for the lungs, pancreas, and urinary bladder, with differences of 48, 53, and 60, respectively. The critical organ was the small intestine with a dose of 25 ?Sv/MBq. The effective doses (EDs) calculated from imaging-based and organ-harvesting-derived data were 5.5 and 5.6 ?Sv/MBq, respectively, using the International Commission on Radiological Protection 60 tissue weighting factors.

Conclusions

The ED of [¹¹C]preladenant (2 mSv for a 370-MBq injected dose) is comparable with other C-11-labeled PET tracers. Estimation of the radiation dosimetry of [¹¹C]preladenant by PET/CT imaging in rats is feasible and gives comparable results to organ harvesting, provided that small VOIs are used and the content of hollow organs is taken into account. Dosimetry by PET imaging can strongly reduce the number of laboratory animals required.

SUBMITTER: Zhou X

PROVIDER: S-EPMC5336543 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

Radiation Dosimetry of a Novel Adenosine A<sub>2A</sub> Receptor Radioligand [<sup>11</sup>C]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats.

Zhou Xiaoyun X Elsinga Philip H PH Khanapur Shivashankar S Dierckx Rudi A J O RA de Vries Erik F J EF de Jong Johan R JR

Molecular imaging and biology 20170401 2

<h4>Purpose</h4>[<sup>11</sup>C]Preladenant was developed as a novel adenosine A<sub>2A</sub> receptor PET radioligand. The aim of this study was to determine the radiation dosimetry of [<sup>11</sup>C]preladenant and to investigate whether dosimetry estimation based on organ harvesting can be replaced by positron emission tomography (PET)/x-ray computed tomography (CT) imaging in rats.<h4>Procedures</h4>Male Wistar rats (n = 35) were i.v. injected with [<sup>11</sup>C]preladenant. The tracer bi ...[more]

PMID: 27539309

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Project description:BackgroundThe NMDA receptor (NMDAR) plays a key role in the central nervous system, e.g., for synaptic transmission. While synaptic NMDARs are thought to have protective characteristics, activation of extrasynaptic NMDARs might trigger excitotoxic processes linked to neuropsychiatric disorders. Since extrasynaptic NMDARs are typically GluN2B-enriched, the subunit is an interesting target for drug development and treatment monitoring. Recently, the novel GluN2B-specific PET radioligand (R)-[11C]Me-NB1 was investigated in rodents and for the first time successfully translated to humans. To assess whether (R)-[11C]Me-NB1 is a valuable radioligand for (repeated) clinical applications, we evaluated its safety, biodistribution and dosimetry.MethodsFour healthy subjects (two females, two males) underwent one whole-body PET/MR measurement lasting for more than 120 min. The GluN2B-specific radioligand (R)-[11C]Me-NB1 was administered simultaneously with the PET start. Subjects were measured in nine passes and six bed positions from head to mid-thigh. Regions of interest was anatomically defined for the brain, thyroid, lungs, heart wall, spleen, stomach contents, pancreas, liver, kidneys, bone marrow and urinary bladder contents, using both PET and MR images. Time-integrated activity coefficients were estimated to calculate organ equivalent dose coefficients and the effective dose coefficient. Additionally, standardized uptake values (SUV) were computed to visualize the biodistribution.ResultsAdministration of the radioligand was safe without adverse events. The organs with the highest uptake were the urinary bladder, spleen and pancreas. Organ equivalent dose coefficients were higher in female in almost all organs, except for the urinary bladder of male. The effective dose coefficient was 6.0 µSv/MBq.ConclusionThe GluN2B-specific radioligand (R)-[11C]Me-NB1 was well-tolerated without reported side effects. Effective dose was estimated to 1.8 mSv when using 300 MBq of presented radioligand. The critical organ was the urinary bladder. Due to the low effective dose coefficient of this radioligand, longitudinal studies for drug development and treatment monitoring of neuropsychiatric disorders including neurodegenerative diseases are possible. Trial registration Registered on 11th of June 2019 at https://www.basg.gv.at (EudraCT: 2018-002933-39).

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Dataset Information

Radiation Dosimetry of a Novel Adenosine A_2A Receptor Radioligand [¹¹C]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats.

Purpose

Procedures

Results

Conclusions

Publications

Radiation Dosimetry of a Novel Adenosine A<sub>2A</sub> Receptor Radioligand [<sup>11</sup>C]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats.

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Dataset Information

Radiation Dosimetry of a Novel Adenosine A2A Receptor Radioligand [11C]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats.

Purpose

Procedures

Results

Conclusions

Publications

Radiation Dosimetry of a Novel Adenosine A<sub>2A</sub> Receptor Radioligand [<sup>11</sup>C]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Radiation Dosimetry of a Novel Adenosine A_2A Receptor Radioligand [¹¹C]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats.