Related Experiment Video
Updated: Jul 13, 2025
Enhancing Efficiency and Radiolabeling Yields of Carbon-11 Radioligands for Clinical Research Using the Loop Method
Published on: December 20, 2024
Development of Novel 11C-Labeled Selective Orexin-2 Receptor Radioligands for Positron Emission Tomography Imaging
Jian Rong1,2, Tomoteru Yamasaki3, Yinlong Li1,2
1Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia 30322, United States.
Abstract:
Orexin 2 receptors (OX2R) represent a vital subtype of orexin receptors intricately involved in the regulation of wakefulness, arousal, and sleep-wake cycles. Despite their importance, there are currently no positron emission tomography (PET) tracers available for imaging the OX2R in vivo. Herein, we report [11C]1 ([11C]OX2-2201) and [11C]2 ([11C]OX2-2202) as novel PET ligands. Both compounds 1 (K i = 3.6 nM) and 2 (K i = 2.2 nM) have excellent binding affinity activities toward OX2R and target selectivity (OX2/OX1 > 600 folds). In vitro autoradiography in the rat brain suggested good to excellent in vitro binding specificity for [11C]1 and [11C]2. PET imaging in rat brains indicated that the low brain uptake of [11C]2 may be due to P-glycoprotein and/or breast cancer resistance protein efflux interaction and/or low passive permeability. Continuous effort in medicinal chemistry optimization is necessary to improve the brain permeability of this scaffold.
Insights
Researchers developed novel positron emission tomography (PET) ligands, [11C]OX2-2201 and [11C]OX2-2202, for imaging orexin 2 receptors (OX2R) in vivo. These ligands show high affinity and selectivity, but further optimization is needed for brain penetration.
Area of Science:
- Neuroscience
- Radiochemistry
- Pharmacology
Background:
- Orexin 2 receptors (OX2R) are crucial for regulating wakefulness and sleep-wake cycles.
- Currently, no positron emission tomography (PET) tracers exist for in vivo imaging of OX2R.
Purpose of the Study:
- To develop and characterize novel PET ligands for imaging OX2R in vivo.
- To evaluate the binding affinity, selectivity, and brain uptake of the novel tracers.
Main Methods:
- Synthesis and radiolabeling of two novel PET ligands, [11C]OX2-2201 and [11C]OX2-2202.
- In vitro binding assays to determine affinity (Ki) and selectivity (OX2/OX1 ratio).
- In vitro autoradiography and in vivo PET imaging in rat brains to assess binding specificity and brain uptake.
Main Results:
- Both [11C]OX2-2201 and [11C]OX2-2202 demonstrated excellent binding affinity (Ki = 3.6 nM and 2.2 nM, respectively) and high selectivity for OX2R (OX2/OX1 > 600 folds).
- In vitro autoradiography showed good to excellent binding specificity in rat brains.
- In vivo PET imaging revealed low brain uptake for [11C]OX2-2202, potentially due to efflux transporter interactions or low passive permeability.
Conclusions:
- [11C]OX2-2201 and [11C]OX2-2202 are promising novel PET ligands for OX2R with high affinity and selectivity.
- Further medicinal chemistry optimization is required to enhance brain penetration for future in vivo applications.
![Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F59557.jpg&w=3840&q=50)
Related Concept Videos
01:29Positron Emission Tomography
One of the main requirements of a PET scan is a positron-emitting radioisotope, which is produced in a cyclotron and then attached to a substance used by the part of the body...
01:25Imaging Studies II: Positron Emission Tomography and Scintigraphy
Fundamental Principles of PET