Theranostics 2017; 7(6):1422-1436. doi:10.7150/thno.17666 This issue Cite

Research Paper

[18F]GE-180 PET Detects Reduced Microglia Activation After LM11A-31 Therapy in a Mouse Model of Alzheimer's Disease

Michelle L. James1,2*✉, Nadia P. Belichenko2*, Adam J. Shuhendler1, Aileen Hoehne1, Lauren E. Andrews1, Christina Condon2, Thuy-Vi V. Nguyen2, Vladimer Reiser3, Paul Jones4, William Trigg4, Jianghong Rao1, Sanjiv S. Gambhir1, Frank M. Longo2✉

1. Department of Radiology, Stanford University, Stanford, 94305, USA;
2. Department of Neurology and Neurological Sciences, Stanford University, Stanford, 94305, USA;
3. GE Healthcare, Life Sciences, Marlborough, MA 01752, USA;
4. GE Healthcare, Amersham HP7 9LL, United Kingdom.
*These authors contributed equally to this work

Citation:
James ML, Belichenko NP, Shuhendler AJ, Hoehne A, Andrews LE, Condon C, Nguyen TVV, Reiser V, Jones P, Trigg W, Rao J, Gambhir SS, Longo FM. [18F]GE-180 PET Detects Reduced Microglia Activation After LM11A-31 Therapy in a Mouse Model of Alzheimer's Disease. Theranostics 2017; 7(6):1422-1436. doi:10.7150/thno.17666. https://www.thno.org/v07p1422.htm
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Abstract

Graphic abstract

Microglial activation is a key pathological feature of Alzheimer's disease (AD). PET imaging of translocator protein 18 kDa (TSPO) is a strategy to detect microglial activation in vivo. Here we assessed flutriciclamide ([18F]GE-180), a new second-generation TSPO-PET radiotracer, for its ability to monitor response to LM11A-31, a novel AD therapeutic in clinical trials. AD mice displaying pathology were treated orally with LM11A-31 for 3 months. Subsequent [18F]GE-180-PET imaging revealed significantly lower signal in cortex and hippocampus of LM11A-31-treated AD mice compared to those treated with vehicle, corresponding with decreased levels of TSPO immunostaining and microglial Iba1 immunostaining. In addition to detecting decreased microglial activation following LM11A-31 treatment, [18F]GE-180 identified activated microglia in AD mice with greater sensitivity than another second-generation TSPO radiotracer, [18F]PBR06. Together, these data demonstrate the promise of [18F]GE-180 as a potentially sensitive tool for tracking neuroinflammation in AD mice and for monitoring therapeutic modulation of microglial activation.

Keywords: Alzheimer's disease, [18F]GE-180, flutriciclamide, neuroinflammation, PET, TSPO, LM11A-31.


Citation styles

APA
James, M.L., Belichenko, N.P., Shuhendler, A.J., Hoehne, A., Andrews, L.E., Condon, C., Nguyen, T.V.V., Reiser, V., Jones, P., Trigg, W., Rao, J., Gambhir, S.S., Longo, F.M. (2017). [18F]GE-180 PET Detects Reduced Microglia Activation After LM11A-31 Therapy in a Mouse Model of Alzheimer's Disease. Theranostics, 7(6), 1422-1436. https://doi.org/10.7150/thno.17666.

ACS
James, M.L.; Belichenko, N.P.; Shuhendler, A.J.; Hoehne, A.; Andrews, L.E.; Condon, C.; Nguyen, T.V.V.; Reiser, V.; Jones, P.; Trigg, W.; Rao, J.; Gambhir, S.S.; Longo, F.M. [18F]GE-180 PET Detects Reduced Microglia Activation After LM11A-31 Therapy in a Mouse Model of Alzheimer's Disease. Theranostics 2017, 7 (6), 1422-1436. DOI: 10.7150/thno.17666.

NLM
James ML, Belichenko NP, Shuhendler AJ, Hoehne A, Andrews LE, Condon C, Nguyen TVV, Reiser V, Jones P, Trigg W, Rao J, Gambhir SS, Longo FM. [18F]GE-180 PET Detects Reduced Microglia Activation After LM11A-31 Therapy in a Mouse Model of Alzheimer's Disease. Theranostics 2017; 7(6):1422-1436. doi:10.7150/thno.17666. https://www.thno.org/v07p1422.htm

CSE
James ML, Belichenko NP, Shuhendler AJ, Hoehne A, Andrews LE, Condon C, Nguyen TVV, Reiser V, Jones P, Trigg W, Rao J, Gambhir SS, Longo FM. 2017. [18F]GE-180 PET Detects Reduced Microglia Activation After LM11A-31 Therapy in a Mouse Model of Alzheimer's Disease. Theranostics. 7(6):1422-1436.

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