[11C]-DPA-713 and [18F]-DPA-714 as New PET Tracers for TSPO: A Comparison with [11C]-(R)-PK11195 in a Rat Model of Herpes Encephalitis

Background: Activation of microglia cells plays an important role in neurological diseases. Positron emission tomography (PET) with [C-11]-(R)-PK11195 has already been used to visualize activated microglia cells in neurological diseases. However, [C-11]-(R)-PK11195 may not possess the required sensitivity to visualize mild neuroinflammation. In this study, we evaluated the PET tracers [C-11]-DPA-713 and [F-18]-DPA-714 as agents for imaging of activated microglia in a rat model of herpes encephalitis. Materials and Methods: Rats were intranasally inoculated with HSV-1. On day 6 or 7 after inoculation, small animal PET studies were performed to compare [C-11]-(R)-PK11195, [C-11]-DPA-713, and [F-18]-DPA-714. Results: Uptake of [C-11]-DPA-713 in infected brain areas was comparable to that of [C-11]-(R)-PK11195, but [C-11]-DPA-713 showed lower non-specific binding. Non-specific uptake of [F-18]-DPA-714 was lower than that of [C-11]-(R)-PK11195. In the infected brain, total [F-18]-DPA-714 uptake was lower than that of [C-11]-(R)-PK11195, with comparable specific uptake. Conclusions: [C-11]-DPA-713 may be more suitable for visualizing mild inflammation than [C-11]-(R)-PK11195. In addition, the fact that [F-18]-DPA-714 is an agonist PET tracer opens new possibilities to evaluate different aspects of neuroinflammation. Therefore, both tracers warrant further investigation in animal models and in a clinical setting

Development of a tracer kinetic plasma input model for (R)-[11C]PK11195 brain studies

(R)-[11C]PK11195 ([1-(2-chlorophenyl)-N-methyl-N-(1- methylpropyl]-3-isoquinoline carboxamide) is a ligand for the peripheral benzodiazepine receptor, which, in the brain, is mainly expressed on activated microglia. Using both clinical studies and Monte Carlo simulations, the aim of this study was to determine which tracer kinetic plasma input model best describes (R)-[11C]PK11195 kinetics. Dynamic positron emission tomography (PET) scans were performed on 13 subjects while radioactivity in arterial blood was monitored online. Discrete blood samples were taken to generate a metabolite corrected plasma input function. One-tissue, two-tissue irreversible, and two-tissue reversible compartment models, with and without fixing K1/k2 ratio, k4, or blood volume to whole cortex values, were fitted to the data. The effects of fixing parameters to incorrect values were investigated by varying them over a physiologic range and determining accuracy and reproducibility of binding potential and volume of distribution using Monte Carlo simulations. Clinical data showed that a two-tissue reversible compartment model was optimal for analyzing (R)-[ 11C]PK11195 PET brain studies. Simulations showed that fixing the K1/k2 ratio of this model provided the optimal trade-off between accuracy and reproducibility. It was concluded that a two-tissue reversible compartment model with K1/k2 fixed to whole cortex value is optimal for analyzing (R)-[11C]PK11195 PET brain studies

Intima media thickness as a predictor of atherosclerosis in renal transplantation

Joint Meeting of the Turkish-Transplantation-Society and Eurotransplant -- JUN 25-27, 2003 -- ANKARA, TURKEYWOS: 000188758100047PubMed ID: 15013331It has been reported that an increase in carotid artery intima-media thickness (IMT), a sign of early atherosclerosis, has a predictive value for future cardiovascular (CV) events. There are limited data about IMT measurements in renal transplant patients who display a high rate of CV mortality. In this study carotid artery IMT was measured by high resolution B-mode ultrasonography in 102 randomly selected RT patients to assess the relationship between IMT and CV disease and risk factors. A positive correlation was found between IMT and age, triglyceride level, and hematocrit. IMT was significantly higher among patients who were diabetic (0.68 +/- 0.27 vs 0.50 +/- 0.2) or had CV disease (0.88 +/- 0.28 vs 0.53 +/- 0.21). An increased IMT was associated with a longer duration of ESRD, higher lipid level, lower serum albumin, and presence of previous CMV disease. CV disease was more frequent among patients with increased IMT. Considering its relation to CV risk factors, it is concluded that the measurement of carotid artery IMT is an easy, reliable and non-invasive method to be used to assess atherosclerotic disease in renal transplant patients.Turkish Transplantat Soc, Eurotransplan