%0 Journal Article %A Yeona Kang %A Anastasia Nikolopoulou %A David Schlyer %A Wenchao Qu %A Paresh Kothari %A John Babich %T Alteration of Blood Brain Barrier during Cuprizone-Induced Neuroinflammation using multi-tracers with PET: [68Ga]EDTA, [11C](R)PK11195, and [11C]DPA713 %D 2018 %J Journal of Nuclear Medicine %P 342-342 %V 59 %N supplement 1 %X 342Objectives: Radiotracers that bind to TSPO are frequently used as a measure of neuroinflammation and obtaining accurate estimates is an important consideration in understanding neurodegenerative diseases. However, alteration of Blood-Brain Barrier (BBB) may affect the uptake rate and therefore confound the measurement. In this study, we tested the changes of influx rate (K1) to changes in the levels of neuroinflammation using the curprizone rat model that is a well-known animal model for multiple sclerosis. Methods: Six male SD rats were fed with curpizone, that is known to lead to oligodendrocyte death with subsequent reversible demyelination. Dynamic 60-min scans with [68Ga]EDTA (EDTA), [11C](R)PK11195 (PK) and [11C]DPA713 (DPA) were performed at baseline and then again at 4 to 6 weeks after initiation of curprizone chow. EDTA images were analyzed to quantify influx rate (K1) and distribution volume (VT) using one a compartment model and vena cava to determine image-derived input function (IDIF). PK and DPA images were analyzed using Logan graphical model with IDIF to measure VT. Results: Good correlation of the values of VT between PK and DPA was found at both time points tested: 0.82 (p=0.05) at baseline, and 0.91 (p=0.01) at week 4-6. In addition, a ~30% increase in uptake was evident for both tracers as a result of cuprizone treatment. The mean of PK-VT was 0.93±0.27 at baseline and 1.27±0.47 at 4-6 weeks with p=0.1. The mean of DPA-VT was 0.65±0.29 at baseline and 0.91±0.21 at 4-6 weeks with p=0.05. EDTA PET imaging showed a significant increase in K1at week 6 (0.07±0.01 at baseline and 0.14±0.01 at week 6; p=0.001) however no significant difference in VT (p=0.1). Conclusions: Our data show that neuroinflammation induced by the copper chelator cuprizone resulted in a significant increase in the uptake of both [11C](R)PK11195 and [11C]DPA713. The EDTA demonstrated a significant change in influx rate during cuprizone-induced neuroinflammation which may be attributed to changes in the BBB permeability, but may also be a result of changes in blood flow. %U