PT  - JOURNAL ARTICLE
AU  - Alexander K. Converse
AU  - Eric C. Larsen
AU  - Jonathan W. Engle
AU  - Todd E. Barnhart
AU  - Robert J. Nickles
AU  - Ian D. Duncan
TI  - <sup>11</sup>C-(<em>R</em>)-PK11195 PET Imaging of Microglial Activation and Response to Minocycline in Zymosan-Treated Rats
AID  - 10.2967/jnumed.110.082743
DP  - 2011 Feb 01
TA  - Journal of Nuclear Medicine
PG  - 257--262
VI  - 52
IP  - 2
4099  - http://jnm.snmjournals.org/content/52/2/257.short
4100  - http://jnm.snmjournals.org/content/52/2/257.full
SO  - J Nucl Med2011 Feb 01; 52
AB  - We sought to advance methodology for studying microglial activation and putative therapeutic downregulation in response to minocycline by means of noninvasive in vivo imaging. A reproducible focal white matter lesion was used to reliably compare treatment conditions. Methods: The corpus callosum of female Sprague Dawley rats was injected with zymosan to promote microglial activation as confirmed by hematoxylin and eosin staining, 3H-PK11195 autoradiography, and CD11b immunohistochemistry. A subset of subjects was treated systemically with minocycline to potentially alter microglial activation. Seven days after zymosan injection, subjects were imaged with PET using the radiotracer 11C-(R)-PK11195. In vivo binding was evaluated using the distribution volume ratio (DVR) with respect to a reference region. Results: At the lesion site, the observed 11C-(R)-PK11195 DVR for each treatment was as follows: mean saline DVR ± SD, 1.17 ± 0.05 (n = 5); zymosan-only DVR, 1.96 ± 0.33 (n = 10); and zymosan with minocycline DVR, 1.58 ± 0.12 (n = 9). Therefore, compared with controls, zymosan increased binding (P = 0.0001, 2-tailed t test) and minocycline treatment reduced zymosan-induced binding by 46% (P = 0.004, 2-tailed t test). Conclusion: Zymosan-induced microglial activation and its response to minocycline can be quantitatively imaged in the rat brain using 11C-(R)-PK11195 PET. The ability to detect a treatment effect in a focal white-matter lesion may be of use in studying therapies for multiple sclerosis (MS).