Preclinical evaluation and quantification of 18F-FPEB as a radioligand for PET imaging of the metabotropic XXXX receptor 5.

@entity3264 @entity10092 @entity2100 @entity161 @entity35 @entity73277
UNASSIGNED: The metabotropic @entity3264 receptor 5 ( @entity10092 ) is a high interest target for PET imaging as it plays a role in several pathologies, including addiction, @entity161 and @entity2100 . METHODS: We studied the pharmacokinetics of @entity73277 , a selective PET radioligand for @entity10092 , and used it to quantify @entity10092 in @entity35 brain. Quantification was performed using both arterial sampling in combination with compartment models as well as simplified reference methods. SRTM, MRTM0, and Logan Non-Invasive were tested as reference models with BPND as outcome parameter. Additionally, test-retest scans were performed in six animals. RESULTS: @entity73277 uptake in @entity35 brain was consistent with its known distribution. No radiometabolites were present in the brain and binding was specific as shown in blocking experiments, which also confirmed the cerebellum as a viable reference region. A two tissue compartment model was used to determine BPND for the striatum (11.7  1.5), nucleus accumbens (10.6  2.0), hippocampus (9.0  1.2), cortex (7.2  1.0) and thalamus (4.0  0.9). Reference methods were able to estimate these values with small bias (<2%). Test-retest analysis showed high repeatability between scans below 6 %, also for shorter scan durations of 30 and 60 min. CONCLUSION: Due to its favorable reversible kinetics, high specificity and absence of brain radiometabolites @entity73277 proves a highly useful tracer for in vivo visualization of the @entity10092 in @entity35 brain. Moreover, reference tissue models allow non-invasive, rapid scanning with good test-retest.
