Initial evaluation of 11C-DPA-713, a novel TSPO PET ligand, in humans.
Translocator protein (TSPO) is upregulated in activated microglia and thus can serve as a marker of neuroinflammation. Recently, a novel radioligand, (11)C-N,N-diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-acetamide ((11)C-DPA-713), has been described that binds to TSPO with high affinity. Here, we report the first examination of (11)C-DPA-713 in human subjects using PET.


METHODS
Five healthy controls were studied with PET for 90 min after a bolus injection of high-specific-activity (11)C-DPA-713. For comparison, 2 additional healthy controls were studied with (11)C-R-PK11195. Arterial blood sampling and metabolite analysis were performed to allow the accurate quantification of tracer kinetics. Tracer uptake was evaluated for several brain regions. Tissue time-activity curves were fitted using 1- and 2-tissue-compartment models, with goodness-of-fit tests showing a preference for the 2-tissue model.


RESULTS
In the healthy brain, the average plasma-to-tissue clearance and the total volume of distribution were an order of magnitude larger than measured for (11)C-R-PK11195. Accordingly, dose-normalized time-activity curves showed that (11)C-DPA-713 gives a larger brain signal.


CONCLUSIONS
Studies in patient populations will help determine whether (11)C-DPA-713 provides better sensitivity for evaluating increased TSPO expression. This initial study in humans shows that (11)C-DPA-713 is a promising ligand for evaluating TSPO binding with PET.
Endres
Christopher J
CJ
Division of Neuroradiology, Johns Hopkins University, Baltimore, Maryland 21231, USA. endres@jhmi.edu
Pomper
Martin G
MG
James
Michelle
M
Uzuner
Ovsev
O
Hammoud
Dima A
DA
Watkins
Crystal C
CC
Reynolds
Aaron
A
Hilton
John
J
Dannals
Robert F
RF
Kassiou
Michael
M
D000081:Acetamides / Q000493:pharmacokinetics*; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018079:Receptors, GABA / Q000378:metabolism*; D014018:Tissue Distribution
D000081:Acetamides; D002250:Carbon Radioisotopes; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human