Insights into the development of 99mTc-radioligands for serotonergic receptors imaging: Synthesis, labeling, In vitro, and In vivo studies

Shahnaz Saednia; Saeed Emami; Masoud Moslehi; Seyed Jalal Hosseinimehr

doi:10.1016/j.ejmech.2024.116349

Insights into the development of ^99mTc-radioligands for serotonergic receptors imaging: Synthesis, labeling, In vitro, and In vivo studies

Eur J Med Chem. 2024 Apr 15:270:116349. doi: 10.1016/j.ejmech.2024.116349. Epub 2024 Mar 23.

Authors

Shahnaz Saednia¹, Saeed Emami², Masoud Moslehi³, Seyed Jalal Hosseinimehr⁴

Affiliations

¹ Farabi Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
² Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
³ Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
⁴ Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: sjhosseinim@yahoo.com.

PMID: 38555856
DOI: 10.1016/j.ejmech.2024.116349

Abstract

Serotonergic (5-hydroxytryptamine; 5-HT) receptors play critical roles in neurological and psychological disorders such as schizophrenia, anxiety, depression, and Alzheimer's diseases. Therefore, it is particularly important to develop novel radioligands or modify the existing ones to identify the serotonergic receptors involved in psychiatric disorders. Among the 16 subtypes of serotonergic systems, only technetium-99m based radiopharmaceuticals have been evaluated for serotonin-1A (5-HT_1A), serotonin-2A (5-HT_2A), 5-HT_1A/7 heterodimers and serotonin receptor neurotransmitter (SERT). This review focuses on recent efforts in the design, synthesis and evaluation of ^99mTc-radioligands used for single photon emission computerized tomography (SPECT) imaging of serotonergic (5-HT) receptors. Additionally, the discussion will cover aspects such as chemical structure, in vitro/vivo stability, affinity toward serotonin receptors, blood-brain barrier permeation (BBB), and biodistribution study.

Keywords: (99m)Tc-radioligands; Molecular imaging; SPECT imaging; Serotonergic systems; Technetium-99m.

Publication types

Review

MeSH terms

Blood-Brain Barrier / metabolism
Brain* / metabolism
Humans
Radiopharmaceuticals / chemistry
Receptors, Serotonin / metabolism
Serotonin*
Technetium / chemistry
Tissue Distribution
Tomography, Emission-Computed, Single-Photon / methods

Substances

Serotonin
Radiopharmaceuticals
Technetium
Receptors, Serotonin