| Autor: |
Taubel JC; Division of Nuclear Medicine, Department of Radiology, Mayo Clinic Rochester, Minnesota 55905, United States., Nelson NR; Division of Nuclear Medicine, Department of Radiology, Mayo Clinic Rochester, Minnesota 55905, United States., Bansal A; Division of Nuclear Medicine, Department of Radiology, Mayo Clinic Rochester, Minnesota 55905, United States., Curran GL; Division of Nuclear Medicine, Department of Radiology, Mayo Clinic Rochester, Minnesota 55905, United States., Wang L; Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States., Wang Z; Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States., Berg HM; Division of Nuclear Medicine, Department of Radiology, Mayo Clinic Rochester, Minnesota 55905, United States., Vernon CJ; Division of Nuclear Medicine, Department of Radiology, Mayo Clinic Rochester, Minnesota 55905, United States., Min HK; Division of Nuclear Medicine, Department of Radiology, Mayo Clinic Rochester, Minnesota 55905, United States., Larson NB; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota 55905, United States., DeGrado TR; Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States., Kandimalla KK; Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States., Lowe VJ; Division of Nuclear Medicine, Department of Radiology, Mayo Clinic Rochester, Minnesota 55905, United States., Pandey MK; Division of Nuclear Medicine, Department of Radiology, Mayo Clinic Rochester, Minnesota 55905, United States. |
| Abstrakt: |
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. Herein, we describe the development of an insulin-based novel positron emission tomography (PET) probe, [ 68 Ga]Ga-NOTA-insulin, to noninvasively study the role of insulin in AD. The developed PET probe [ 68 Ga]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. In addition, [ 68 Ga]Ga-NOTA-insulin was found to have a differential uptake in various brain regions at 30 min post injection. Among the brain regions, the cortex, thalamus, brain stem, and cerebellum showed a significantly higher standard uptake value (SUV) of [ 68 Ga]Ga-NOTA-insulin in AD mice as compared to normal mice. The inhibition of the insulin receptor (IR) with an insulin receptor antagonist peptide (S961) in normal mice showed a similar brain uptake profile of [ 68 Ga]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. The Gjedde-Patlak graphical analysis was also performed to predict the input rate of [ 68 Ga]Ga-NOTA-insulin into the brain using MicroPET imaging data and supported the in vivo results. The [ 68 Ga]Ga-NOTA-insulin PET probe was successfully synthesized and evaluated in a mouse model of AD in comparison with [ 18 F]AV1451 and [ 11 C]PIB to noninvasively study the role of insulin in AD pathophysiology. |
