Preliminary biological evaluations of first brain‐penetrant GPR119‐based radiotracer in rodents and non‐human primates

Background G‐protein‐coupled receptors (GPCRs) plays a key role in regulating glucose metabolism. While GPR119 (an important GPCR) agonists have shown potential for improving neurologic and cognitive function in patients with AD and type2 diabetes mellitus (T2DM), clinical interventions targeting GP...

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Published in:Alzheimer's & dementia 2023-06, Vol.19 (S3), p.n/a
Main Authors: Bansode, Avinash, Damuka, Naresh, Krizan, Ivan, Miller, Mack, Bashetti, Nagaraju, Kumar, JV Shanmukha, Ma, Tao, Shively, Carol A., Lockhart, Samuel N., Whitlow, Christopher T., Craft, Suzanne, Jorgensen, Matthew J., Sai, Kiran K Solingapuram
Format: Article
Language:English
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Summary:Background G‐protein‐coupled receptors (GPCRs) plays a key role in regulating glucose metabolism. While GPR119 (an important GPCR) agonists have shown potential for improving neurologic and cognitive function in patients with AD and type2 diabetes mellitus (T2DM), clinical interventions targeting GPR119 will require accurate in vivo measures such as PET imaging. We recently synthesized a series of novel piperdine analogs, identifying two analogs (T1 and T2) with high GPR119 binding potency (2‐5 nM) for PET radiochemistry. Here we report their radiochemistry and initial biological evaluations in neuronal cells, normal rodents, and monkeys (vervets). Method [18F]T1/T2 radiochemistry was performed in TRASIS‐AIO automated module following [18F]¯‐based nucleophilic substitution of corresponding precursors. [18F]T1 and T2 in vitro assays were performed in three patient‐derived cell lines with different GPR119 expression (MDM‐MD‐231
ISSN:1552-5260
1552-5279
DOI:10.1002/alz.063987