Authors:  Priya Singh, Deepika Singh, Anupriya Adhikari, Anjani Kumar Tiwari*

Department of Applied Chemistry & Nuclear Medicine, Babasaheb Bhimrao Ambedkar Univerity, Lucknow, India 226025

Background

In search of new ligand for  translator protein (TSPO, 18 kDa) which is a known inflammatory and oncological marker and present mainly on outer surface of mitochondria in microglial cells of brain and other peripheral organs such as kidney, lungs, liver, and spleen, a new modified benzoxazolone has been synthesized and compared with Luminescent nanoprobe of TSPO.

Aims

We have synthesised improved acetamidobenzoxazolone derivatised radioprobe for visualization of 18 kDa TSPO which is able to overcome the limitation of previous generation ligands as well as comparison of sensitivity and specificity with TSPO specific nanoprobes.

Methods

Computational analysis was performed by Glide, Schrodinger to designated ligand. Reference molecules as well as nano probes were synthesised in wet lab and characterized by different spectroscopic techniques. Mild focal ischemia (MFI) produced by intraluminal occlusion of the middle cerebral artery of SD rats by intraluminal thread model were used for ARG and PET studies.

Results and Conclusion

In conclusion, we demonstrated that our synthesized PET radioprobe [¹¹C]N_eBMP shows radiopharmaceutical profile for imaging of PBR/TSPO expression during neuroinflammation and comparable to nanoprobes . Further opti-mization may lead to a new ligand for clinics for TSPO imaging having minimal impact by TSPO rs6971.

1. Fujinaga M. et al, Development of a ¹⁸F-labeled radioligand with improved brain kinetics for positron emission tomography imaging of translocator protein  (18 kDa)  in ischemic brain and glioma. J Med Chem. 2017, 60, 4047−4061. 

2. Tiwari A. K. et al, [¹⁸F]FEBMP: Positron Emission Tomography Imaging of TSPO in a Model of Neuroinflammation in Rats, and in vitro Autoradiograms of the Human Brain. Theranostics 2015, 5, 961−969.

3. Tiwari A. K. et al, Radiosynthesis and evaluation of acetamidobenzoxazolone based radioligand [¹¹C]N′-MPB for visualization of 18 kDa TSPO in brain. New J. Chem., 2020,44, 7912-7922