![]() In the normal vs AD mouse using heart concentration data. ![]() ![]() Influx clearance and ligand binding with the receptor at the BBB interface (B) Gjedde–Patlak plot describing the Ga-insulin Observed values (mean ± SD, normal: n = 4, AD: n = 3) overlaid with the predictedĬurves are shown. Heart concentration vs time profile of Ga-NOTA-insulin The Ga-NOTA-insulin PET probe was successfully synthesized and evaluated in a mouse model of AD in comparison with AV1451 and PIB to noninvasively study the role of insulin in AD pathophysiology. The Gjedde-Patlak graphical analysis was also performed to predict the input rate of Ga-NOTA-insulin into the brain using MicroPET imaging data and supported the in vivo results. The inhibition of the insulin receptor (IR) with an insulin receptor antagonist peptide (S961) in normal mice showed a similar brain uptake profile of Ga-NOTA-insulin as it was observed in the AD case, suggesting nonfunctional IR in AD and the presence of an alternative insulin uptake route in the absence of a functional IR. Among the brain regions, the cortex, thalamus, brain stem, and cerebellum showed a significantly higher standard uptake value (SUV) of Ga-NOTA-insulin in AD mice as compared to normal mice. In addition, Ga-NOTA-insulin was found to have a differential uptake in various brain regions at 30 min post injection. The developed PET probe Ga-NOTA-insulin showed a significantly higher uptake (0.396 ± 0.055 SUV) in the AD mouse brain compared to the normal (0.140 ± 0.027 SUV) mouse brain at 5 min post injection and also showed a similar trend at 10, 15, and 20 min post injection. Herein, we describe the development of an insulin-based novel positron emission tomography (PET) probe, Ga-NOTA-insulin, to noninvasively study the role of insulin in AD. Aberrant insulin signaling has been considered one of the risk factors for the development of Alzheimer's disease (AD) and has drawn considerable attention from the research community to further study its role in AD pathophysiology.
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