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Synthesis and preliminary evaluation of novel PET probes for GSK-3 imaging

Non-invasive imaging of GSK-3 expression in the brain will help to understand the role of GSK-3 in disease pathology and progression. Herein, we report the radiosynthesis and evaluation of two novel isonicotinamide based 18 F labeled PET probes, [ 18 F] 2 and [ 18 F] 6 for noninvasive imaging of GSK...

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Bibliographic Details
Published in:Scientific reports 2024-07, Vol.14 (1), p.15960-14, Article 15960
Main Authors: Gundam, Surendra Reddy, Bansal, Aditya, Kethamreddy, Manasa, Ghatamaneni, Sujala, Lowe, Val J., Murray, Melissa E., Pandey, Mukesh K.
Format: Article
Language:English
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Summary:Non-invasive imaging of GSK-3 expression in the brain will help to understand the role of GSK-3 in disease pathology and progression. Herein, we report the radiosynthesis and evaluation of two novel isonicotinamide based 18 F labeled PET probes, [ 18 F] 2 and [ 18 F] 6 for noninvasive imaging of GSK3. Among the developed PET probes, the in vitro blood–brain permeability coefficient of 2 (38 ± 20 × 10 –6  cm/s, n  = 3) was found to be better than 6 ( 8.75 ± 3.90 × 10 –6  cm/s, n  = 5). The reference compounds 2 and 6 showed nanomolar affinity towards GSK-3α and GSK-3β. PET probe [ 18 F] 2 showed higher stability (100%) in mouse and human serums compared to [ 18 F] 6 (67.01 ± 4.93%, n  = 3) in mouse serum and 66.20 ± 6.38%, n  = 3) in human serum at 120 min post incubation. The in vivo imaging and blocking studies were performed in wild-type mice only with [ 18 F] 2 due to its observed stability. [ 18 F] 2 showed a SUV of 0.92 ± 0.28 ( n  = 6) in mice brain as early as 5 min post-injection followed by gradual clearance over time.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-65943-z