RT Journal Article
SR Electronic
T1 A PET Brain Reporter Gene System Based on Type 2 Cannabinoid Receptors
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1102
OP 1109
DO 10.2967/jnumed.110.084426
VO 52
IS 7
A1 Vandeputte, Caroline
A1 Evens, Nele
A1 Toelen, Jaan
A1 Deroose, Christophe M.
A1 Bosier, Barbara
A1 Ibrahimi, Abdelilah
A1 Van der Perren, Anke
A1 Gijsbers, Rik
A1 Janssen, Peter
A1 Lambert, Didier M.
A1 Verbruggen, Alfons
A1 Debyser, Zeger
A1 Bormans, Guy
A1 Baekelandt, Veerle
A1 Van Laere, Koen
YR 2011
UL http://jnm.snmjournals.org/content/52/7/1102.abstract
AB PET of gene expression in the brain may greatly facilitate neuroscience research and potential clinical implementation of gene or cell therapy of central nervous system diseases. To date, no adequate PET reporter system is available for the central nervous system because available tracers either do not cross the intact blood–brain barrier or have high background signals. Here we report the first, to our knowledge, PET reporter system for imaging gene expression in the intact brain. Methods: We selected the human type 2 cannabinoid receptor (hCB2) as a reporter because of its low basal expression in the brain. An inactive mutant (D80N) was chosen so as not to interfere with signal transduction. As a reporter probe we used the 11C-labeled CB2 ligand, 11C-GW405833, which readily crosses the blood–brain barrier. Dual-modality imaging lentiviral and adeno-associated viral vectors encoding both hCB2(D80N) and firefly luciferase or enhanced green fluorescent protein were engineered and validated in cell culture. Next, hCB2(D80N) was locoregionally overexpressed in rat striatum by stereotactic injection of lentiviral and adeno-associated viral vectors. Results: Kinetic PET revealed specific and reversible CB2 binding of 11C-GW405833 in the transduced rat striatum. hCB2 and firefly luciferase expression was followed until 9 mo and showed similar kinetics. Both hCB2 expression and enhanced green fluorescent protein expression were confirmed by immunohistochemistry. Conclusion: Dual-modality imaging viral vectors encoding hCB2(D80N) were engineered, and the reporter system was validated in different animal species. The results support the potential future clinical use of CB2 as a PET reporter in the intact brain.