Biomarkers Consortium - Comparison of Two PET Radioligands to Quantify the Peripheral Benzodiazepine Receptor

The Biomarkers Consortium’s PET Radioligand Project, completed in December 2012, was designed to assess the utility of two newly developed, promising PET radioligands to image and quantify inflammation in the brain as compared to the gold standard tracer, [11C](R)-PK 11195, and to determine the relationship between neuroinflammation and disease severity in Alzheimer’s Disease. This project developed improved, more sensitive PET radioligands with higher binding to the peripheral benzodiazepine receptor. Findings from this study suggest that the [11C]PBR38 ligand, in particular, may be useful in detecting progression from mild cognitive impairment or treatment response in Alzheimer’s Disease. Furthermore, results from this project suggest that neuroinflammation occurs after conversion of mild cognitive impairment to Alzheimer’s Disease and worsens with disease progression, further suggesting that greater inflammation may contribute to the precipitous disease course typically seen in early-onset patients.

Goals

  • To assess the utility of two newly developed, promising PET radioligands to image and quantify inflammation in brain.
  • To determine the relationship between neuroinflammation and disease severity in Alzheimer’s Disease.

Results & Accomplishments

Two publications resulted from this study in 2013. The first publication in the Journal of Cerebral Blood Flow and Metabolism reported that a genetic polymorphism for translocator protein 18kDA affects both in vitro and in vivo radiological binding in human brain to this putative biomarker of inflammation. The second publication, in Brain, suggested that neuroinflammation, indicated by increased [11C]PBR28 binding to TSPO, occurs after conversion of mild cognitive impairment to Alzheimer’s Disease, and worsens with disease progression. The results from this project were also presented at the 2013 AAIC meeting.

Scientific Publications

A genetic polymorphism for translocator protein 18 kDa affects both in vitro and in vivo radioligland binding in human brain to this putative biomarker of neuroinflammation. Kreisl, W. C., Jenko, K. J., Hines, C. S., Lyoo, C. H., Corona, W., Morse, C. L., Zoghbi, S. S., Hyde, T., Kleinman, J. E., Pike, V. W., McMahon, F. J., Innis, R. B., & the Biomarkers Consortium PET Radioligand Project Team. . Journal of Cerebral Blood Flow & Metabolism. 2013; vol. 33: 53-58

In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease. Kreisl W.C., Lyoo C.H., McGwier M., Snow J., Jenko K.J., Kimura N., Corona W., Morse C.L., Zoghbi S.S., Pike V.W., McMahon F.J., Turner R.S., Innis R.B.; Biomarkers Consortium PET Radioligand Project Team. Brain. 2013; 136(7): 2228-38

Posters

PET Radioligand  Binding to Translocator Protein May Mark Conversion from Mild Cognitive Impairment to Alzheimer’s Disease. Kreisl, W., Lyoo, C.H., McGwier, M., Snow, J., Jenko, K., Kimura, N., Corona, W., Morse, C., Zoghbi, S., Pike, V., McMahon, F., Turner, R., Innis, R., The Foundation for NIH Biomarkers Consortium PET Radioligand Project. Alzheimer’s Association International Conference (AAIC) 2013.

Partners

GlaxoSmithKline
Eli Lilly and Company
Merck Serono
Merck Sharp & Dohme Corp.
National Institute of Mental Health (NIMH)
Pfizer Inc
Roche

Contact

Rosa Canet-Aviles, Scientific Program Manager, Neuroscience, rcanet-aviles@fnih.org