Theranostics
2017; 7(6):1422-1436.
doi:10.7150/thno.17666 This issueCite
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
✉ Corresponding authors: Frank M Longo, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA, 94305, USA. E-mail: flongoedu; Phone 650 724-3172; Fax 650 723-7434. Michelle L James, Department of Radiology, Stanford University School of Medicine, CA, 94305, USA E-mail: mljamesedu; Phone 650-721-3324; Fax 650-723-8649.More
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
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.
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.
This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.