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Haider A, Xiao Z, Xia X, et al. Development of a triazolobenzodiazepine-based PET probe for subtype-selective vasopressin 1A receptor imaging. Pharmacol Res. 2021;173:105886doi: 10.1016/j.phrs.2021.105886.
Haider, A., Xiao, Z., Xia, X., Chen, J., Van, R. S., Kuang, S., Zhao, C., Rong, J., Shao, T., Ramesh, P., Aravind, A., Shao, Y., Ran, C., Young, L. J., & Liang, S. H. (2021). Development of a triazolobenzodiazepine-based PET probe for subtype-selective vasopressin 1A receptor imaging. Pharmacological research, 173105886. https://doi.org/10.1016/j.phrs.2021.105886
Haider, Ahmed, et al. "Development of a triazolobenzodiazepine-based PET probe for subtype-selective vasopressin 1A receptor imaging." Pharmacological research vol. 173 (2021): 105886. doi: https://doi.org/10.1016/j.phrs.2021.105886
Haider A, Xiao Z, Xia X, Chen J, Van RS, Kuang S, Zhao C, Rong J, Shao T, Ramesh P, Aravind A, Shao Y, Ran C, Young LJ, Liang SH. Development of a triazolobenzodiazepine-based PET probe for subtype-selective vasopressin 1A receptor imaging. Pharmacol Res. 2021 Nov;173:105886. doi: 10.1016/j.phrs.2021.105886. Epub 2021 Sep 16. PMID: 34536549; PMCID: PMC8581590.
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Pharmacol Res. 2021 Nov;173:105886. doi: 10.1016/j.phrs.2021.105886. Epub 2021 Sep 16.

Development of a triazolobenzodiazepine-based PET probe for subtype-selective vasopressin 1A receptor imaging.

Pharmacological research

Ahmed Haider, Zhiwei Xiao, Xiaotian Xia, Jiahui Chen, Richard S Van, Shi Kuang, Chunyu Zhao, Jian Rong, Tuo Shao, Perla Ramesh, Appu Aravind, Yihan Shao, Chongzhao Ran, Larry J Young, Steven H Liang

Affiliations

  1. Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, United States.
  2. Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, United States; Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  3. Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, United States.
  4. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, United States.
  5. Sambi Pharma Pvt. Ltd., Hyderabad 500060, India.
  6. Silvio O. Conte Center for Oxytocin and Social Cognition, Center for Translational Social Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United Stated.
  7. Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, United States. Electronic address: [email protected].

PMID: 34536549 PMCID: PMC8581590 DOI: 10.1016/j.phrs.2021.105886

Abstract

OBJECTIVES: To enable non-invasive real-time quantification of vasopressin 1A (V1A) receptors in peripheral organs, we sought to develop a suitable PET probe that would allow specific and selective V1A receptor imaging in vitro and in vivo.

METHODS: We synthesized a high-affinity and -selectivity ligand, designated compound 17. The target structure was labeled with carbon-11 and tested for its utility as a V1A-targeted PET tracer by cell uptake studies, autoradiography, in vivo PET imaging and ex vivo biodistribution experiments.

RESULTS: Compound 17 (PF-184563) and the respective precursor for radiolabeling were synthesized in an overall yield of 49% (over 7 steps) and 40% (over 8 steps), respectively. An inhibitory constant of 0.9 nM towards the V1A receptors was measured, while excellent selectivity over the related V1B, V2 and OT receptor (IC

CONCLUSION: We have developed the first V1A-targeted PET ligand that is suitable for subtype-selective receptor imaging in peripheral organs including the liver, heart, pancreas and spleen. Our findings suggest that [

Copyright © 2021 Elsevier Ltd. All rights reserved.

Keywords: Pharmacology; Positron emission tomography; Tracer development; Triazolobenzodiazepines; Vasopressin 1A receptor

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