Brain Glucose Metabolism as a Readout of the Central Nervous System Impact of Cigarette Smoke Exposure and Withdrawal and the Effects of NFL-101, as an Immune-Based Drug Candidate for Smoking Cessation Therapy.

Neuroimaging biomarkers are needed to investigate the impact of smoking withdrawal on brain function. NFL-101 is a denicotinized aqueous extract of tobacco leaves currently investigated as an immune-based smoking cessation therapy in humans. However, the immune response to NFL-101 and its ability to induce significant changes in brain function remain to be demonstrated.

[F]2-fluoro-2-deoxy-sorbitol ([F]FDS) PET imaging repurposed for quantitative estimation of blood-brain barrier permeability in a rat model of Alzheimer's disease.

Numerous studies suggest that blood-brain barrier (BBB) dysfunction may contribute to the progression of Alzheimer's disease (AD). Clinically available neuroimaging methods are needed for quantitative "scoring" of BBB permeability in AD patients. [F]2-fluoro-2-deoxy-sorbitol ([F]FDS), which can be easily obtained from simple chemical reduction of commercial [F]2-fluoro-2-deoxy-glucose ([F]FDG), was investigated as a small-molecule marker of BBB permeability, in a pre-clinical model of AD using in vivo PET imaging.

Imaging quantitative changes in blood-brain barrier permeability using [F]2-fluoro-2-deoxy-sorbitol ([F]FDS) PET in relation to glial cell recruitment in a mouse model of endotoxemia.

The quantitative relationship between the disruption of the blood-brain barrier (BBB) and the recruitment of glial cells was explored in a mouse model of endotoxemia. [F]2-Fluoro-2-deoxy-sorbitol ([F]FDS) PET imaging was used as a paracellular marker for quantitative monitoring of BBB permeability after i.v injection of increasing doses of lipopolysaccharide (LPS) or vehicle (saline, n = 5).

Performance and Sensitivity of [Tc]Tc-sestamibi Compared with Positron Emission Tomography Radiotracers to Measure P-glycoprotein Function in the Kidneys and Liver.

P-glycoprotein (P-gp, encoded in humans by the gene and in rodents by the genes) is a membrane transporter that can restrict the intestinal absorption and tissue distribution of many drugs and may also contribute to renal and hepatobiliary drug excretion. The aim of this study was to compare the performance and sensitivity of currently available radiolabeled P-gp substrates for positron emission tomography (PET) with the single-photon emission computed tomography (SPECT) radiotracer [Tc]Tc-sestamibi for measuring the P-gp function in the kidneys and liver. Wild-type, heterozygous (), and homozygous () knockout mice were used as models of different P-gp abundance in excretory organs.

[C]metoclopramide is a sensitive radiotracer to measure moderate decreases in P-glycoprotein function at the blood-brain barrier.

The efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier limits the cerebral uptake of various xenobiotics. To assess the sensitivity of [C]metoclopramide to measure decreased cerebral P-gp function, we performed [C]metoclopramide PET scans without (baseline) and with partial P-gp inhibition by tariquidar in wild-type, heterozygous and homozygous mice as models with controlled levels of cerebral P-gp expression. Brains were collected to quantify P-gp expression with immunohistochemistry.

Imaging the impact of blood-brain barrier disruption induced by focused ultrasound on P-glycoprotein function.

The P-glycoprotein (P-gp/ABCB1) is a major efflux transporter which impedes the brain delivery of many drugs across the blood-brain barrier (BBB). Focused ultrasound with microbubbles (FUS) enables BBB disruption, which immediate and delayed impact on P-gp function remains unclear. Positron emission tomography (PET) imaging using the radiolabeled substrate [C]metoclopramide provides a sensitive and translational method to study P-gp function at the living BBB.

Validation of a pharmacological imaging challenge using C-buprenorphine and F-2-fluoro-2-deoxy-D-glucose positron emission tomography to study the effects of buprenorphine to the rat brain.

Aim: Buprenorphine mainly acts as an agonist of mu-opioid receptors (mu-OR). High dose buprenorphine does not cause respiratory depression and can be safely administered to elicit typical opioid effects and explore pharmacodynamics. Acute buprenorphine, associated with functional and quantitative neuroimaging, may therefore provide a fully translational pharmacological challenge to explore the variability of response to opioids .

Impact of Cytochrome Induction or Inhibition on the Plasma and Brain Kinetics of [C]metoclopramide, a PET Probe for P-Glycoprotein Function at the Blood-Brain Barrier.

[11C]metoclopramide PET imaging provides a sensitive and translational tool to explore P-glycoprotein (P-gp) function at the blood-brain barrier (BBB). Patients with neurological diseases are often treated with cytochrome (CYP) modulators which may impact the plasma and brain kinetics of [11C]metoclopramide. The impact of the CYP inducer carbamazepine or the CYP inhibitor ritonavir on the brain and plasma kinetics of [11C]metoclopramide was investigated in rats.