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Pre-clinical evaluation of 99mTc-labeled chalcone derivative for amyloid-β imaging post-head trauma

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Abstract

Aβ42 plaque formation is one of the preliminary pathologic events that occur post traumatic brain injury (TBI) which is also among the most noteworthy hallmarks of AD. Their pre symptomatic detection is therefore vital for better disease management. Chalcone–picolinic acid chelator derivative, 6‐({[(6‐carboxypyridin‐2‐yl)methyl](2‐{4‐[(2E)‐3‐[4‐(dimethyl amino)phenyl]prop‐2‐enoyl]phenoxy}ethyl)amino}methyl)pyridine‐2‐carboxylic acid, Py-chal was synthesized to selectively identify amyloid plaques formed post head trauma using SPECT imaging by stable complexation to 99mTc with > 97% efficiency without compromising amyloid specificity. The binding potential of the Py-chal ligand to amyloid plaques remained high as confirmed by in vitro binding assay and photophysical spectra. Further, the Py-chal complex stained amyloid aggregates in the brain sections of rmTBI mice model. In vivo scintigraphy in TBI mice model displayed high uptake followed by high retention while the healthy rabbits displayed higher brain uptake followed by a rapid washout attributed to absence of amyloid plaques. Higher uptake in brain of TBI model was also confirmed by ex vivo biodistribution analysis wherein brain uptake of 3.38 ± 0.2% ID/g at 2 min p.i. was observed for TBI mice model. This was followed by prolonged retention and more than twofold higher activity as compared to sham mice brain. This preliminary data suggests the specificity of the radiotracer for amyloid detection post head trauma and applicability of 99mTc labeled Py-chal complex for TBI-induced β-amyloid SPECT imaging.

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Acknowledgements

The authors are thankful to the Director of the Institute of Nuclear Medicine and Allied Sciences for providing the necessary facilities.

Funding

This work has been supported by Defence Research and Development Organization, Ministry of Defence.

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Authors and Affiliations

  1. Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Delhi, 110054, India

    Garima Mann, Shivani Daksh, Nikhil Kumar, Ankur Kaul, B. G. Roy & Anupama Datta

  2. Department of Chemistry, University of Delhi, Delhi, 110007, India

    Garima Mann & M. Thirumal

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  1. Garima Mann
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  2. Shivani Daksh
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Mann, G., Daksh, S., Kumar, N. et al. Pre-clinical evaluation of 99mTc-labeled chalcone derivative for amyloid-β imaging post-head trauma. J Biol Inorg Chem (2024). https://doi.org/10.1007/s00775-024-02049-x

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