Oral Administration of [F]MC225 for Quantification of P-glycoprotein Function: A Feasibility Study.

Purpose: This preclinical study explored the feasibility of assessing P-glycoprotein (P-gp) function in both brain and gastrointestinal (GI) tract of rats using positron emission tomography (PET) following oral administration of [F]MC225. Different oral administration protocols were evaluated, and radioactivity uptake was compared with uptake following intravenous administration.

Procedures: Twelve male Wistar rats were divided into four groups and subjected to intravenous or oral [F]MC225 administration protocols: G (intravenous route), G (oral administration without fasting), G (oral administration with fasting), and G (oral administration with fasting following administration of the P-gp inhibitor tariquidar).

Caloric restriction reduces proteinuria in male rats with established nephropathy.

Reducing proteinuria is a crucial approach in preventing kidney function loss. Previous preclinical studies indicated that caloric restriction (CR) imposed at a young age protects against age-related proteinuria. However, these studies have not explored CR in established renal disease.

Characterization of a novel model for atherosclerosis imaging: the apolipoprotein E-deficient rat.

Background: The apolipoprotein E-deficient (apoE) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE rat has emerged as an alternative.

Preclinical evaluation of 2-[F]fluorodeoxysorbitol as a tracer for targeted imaging of Enterobacterales infection.

Fluorine-18-fluorodeoxyglucose ([F]FDG) positron emission tomography (F-FDG-PET) is widely used for the detection of inflammatory and infectious diseases. Although this modality has proven to be a useful diagnostic tool, reliable distinction of bacterial infection from sterile inflammation or even from a malignancy remains challenging. Therefore, there is a need for bacteria-specific tracers for PET imaging that facilitate a reliable distinction of bacterial infection from other pathology.

Binding of the Dual-Action Anti-Parkinsonian Drug AG-0029 to Dopamine D and Histamine H Receptors: A PET Study in Healthy Rats.

: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction and a diverse range of nonmotor symptoms. Functional relationships between the dopaminergic and histaminergic systems suggest that dual-action pharmaceuticals like AG-0029 (D/D agonist/H antagonist) could ameliorate both the motor and cognitive symptoms of PD. The current study aimed to demonstrate the interaction of AG-0029 with its intended targets in the mammalian brain using positron emission tomography (PET).

Pharmacokinetic Modeling of [C]GSK-189254, PET Tracer Targeting H Receptors, in Rat Brain.

The histamine H receptor has been considered as a target for the treatment of various central nervous system diseases. Positron emission tomography (PET) studies with the radiolabeled potent and selective histamine H receptor antagonist [C]GSK-189254 in rodents could be used to examine the mechanisms of action of novel therapeutic drugs or to assess changes of regional H receptor density in animal models of neurodegenerative disease. [C]GSK-189254 was intravenously administered to healthy Wistar rats ( = 10), and a 60 min dynamic PET scan was carried out.

Perivascular adipose tissue-derived nitric oxide compensates endothelial dysfunction in aged pre-atherosclerotic apolipoprotein E-deficient rats.

Background And Aims: Atherosclerosis is a major contributor to global mortality and is accompanied by vascular inflammation and endothelial dysfunction. Perivascular adipose tissue (PVAT) is an established regulator of vascular function with emerging implications in atherosclerosis. We investigated the modulation of aortic relaxation by PVAT in aged rats with apolipoprotein E deficiency (ApoE) fed a high-fat diet as a model of early atherosclerosis.

[F]Atorvastatin Pharmacokinetics and Biodistribution in Healthy Female and Male Rats.

Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that are widely used to prevent cardiovascular diseases. However, a series of pleiotropic mechanisms have been associated with statins, particularly with atorvastatin. Therefore, the assessment of [F]atorvastatin kinetics with positron emission tomography (PET) may elucidate the mechanism of action of statins and the impact of sexual dimorphism, which is one of the most debated interindividual variations influencing the therapeutic efficacy.

PET/CT Imaging and Physiology of Mice on High Protein Diet.

Background: High protein (HP) diets have been proposed to reduce body weight in humans. The diets are known to alter energy metabolism, which can affect the quality of [F]FDG PET heart images. In this preclinical study, we therefore explore the impact of a prolonged HP diet on myocardial [F]FDG uptake.

Mapping Arginase Expression with F-Fluorinated Late-Generation Arginase Inhibitors Derived from Quaternary α-Amino Acids.

Arginase hydrolyzes L-arginine and influences levels of polyamines and nitric oxide. Arginase overexpression is associated with inflammation and tumorigenesis. Thus, radiolabeled arginase inhibitors may be suitable PET tracers for staging arginase-related pathophysiologies.

Modular Medical Imaging Agents Based on Azide-Alkyne Huisgen Cycloadditions: Synthesis and Pre-Clinical Evaluation of F-Labeled PSMA-Tracers for Prostate Cancer Imaging.

Since the seminal contribution of Rolf Huisgen to develop the [3+2] cycloaddition of 1,3-dipolar compounds, its azide-alkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azide-alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate-specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to pre-clinical in vivo evaluation of fluorine-18- labeled PSMA-targeting 'F-PSMA-MIC' radiotracers (t =109.

Monitoring the Crosstalk Between the Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 with PET.

Purpose: Ovarian cancer (OC) leads to poor survival rates mainly due to late stage detection and innate or acquired resistance to chemotherapy. Thus, efforts have been made to exploit the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) to treat OC. However, patients eventually become resistant to these treatments as well.

Effect of Dopamine D Receptor Antagonists on [F]-FEOBV Binding.

The interaction of dopaminergic and cholinergic neurotransmission in, e.g., Parkinson's disease has been well established.

Test-Retest Repeatability of [F]MC225-PET in Rodents: A Tracer for Imaging of P-gp Function.

In longitudinal PET studies, animals are repeatedly anesthetized which may affect the repeatability of PET measurements. The aim of this study was to assess the effect of anesthesia on the P-gp function as well as the reproducibility of [F]MC225 PET scans. Thus, dynamic PET scans with blood sampling were conducted in 13 Wistar rats.

Modeling of [F]FEOBV Pharmacokinetics in Rat Brain.

Purpose: [F]Fluoroethoxybenzovesamicol ([F]FEOBV) is a radioligand for the vesicular acetylcholine transporter (VAChT), a marker of the cholinergic system. We evaluated the quantification of [F]FEOBV in rats in control conditions and after partial saturation of VAChT using plasma and reference tissue input models and test-retest reliability.

Procedure: Ninety-minute dynamic [F]FEOBV PET scans with arterial blood sampling were performed in control rats and rats pretreated with 10 μg/kg FEOBV.

Publisher Correction: In vitro imaging of bacteria using F-fluorodeoxyglucose micro positron emission tomography.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Test-Retest Stability of Cerebral 2-Deoxy-2-[F]Fluoro-D-Glucose ([F]FDG) Positron Emission Tomography (PET) in Male and Female Rats.

Purpose: An important issue in rodent imaging is the question whether a mixed population of male and female animals can be used rather than animals of a single sex. For this reason, the present study examined the test-retest stability of positron emission tomography (PET) with 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) in male rats and female rats at different phases of the estrous cycle.

Procedures: Long-Evans rats (age 1 year) were divided into three groups: (1) males (n = 6), (2) females in metestrous (low estrogen levels, n = 9), and (3) females in proestrous (high estrogen levels, n = 7).

In Vivo Quantification of ERβ Expression by Pharmacokinetic Modeling: Studies with F-FHNP PET.

The estrogen receptor (ER) is a target for endocrine therapy in breast cancer patients. Individual quantification of ERα and ERβ expression, rather than total ER levels, might enable better prediction of the response to treatment. We recently developed the tracer 2-F-fluoro-6-(6-hydroxynaphthalen-2-yl)pyridin-3-ol (F-FHNP) for assessment of ERβ levels with PET.

In vitro imaging of bacteria using F-fluorodeoxyglucose micro positron emission tomography.

Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (F-FDG) can be applied to detect infection and inflammation. However, it was so far not known to what extent bacterial pathogens may contribute to the PET signal. Therefore, we investigated whether clinical isolates of frequently encountered bacterial pathogens take up F-FDG in vitro, and whether FDG inhibits bacterial growth as previously shown for 2-deoxy-glucose.

Novel Approach to Repeated Arterial Blood Sampling in Small Animal PET: Application in a Test-Retest Study with the Adenosine A1 Receptor Ligand [(11)C]MPDX.

Purpose: Small animal positron emission tomography (PET) can be used to detect small changes in neuroreceptor availability. This often requires rapid arterial blood sampling. However, current catheterization procedures do not allow repeated blood sampling.

Pharmacokinetic Analysis of 11C-PBR28 in the Rat Model of Herpes Encephalitis: Comparison with (R)-11C-PK11195.

(11)C-PBR28 is a second-generation translocator protein (TSPO) tracer with characteristics supposedly superior to the most commonly used tracer for neuroinflammation, (R)-(11)C-PK11195. Despite its use in clinical research, no studies on the imaging properties and pharmacokinetic analysis of (11)C-PBR28 in rodent models of neuroinflammation have been published yet. Therefore, this study aimed to evaluate (11)C-PBR28 as a tool for detection and quantification of neuroinflammation in preclinical research and to compare its imaging properties with (R)-(11)C-PK11195.

LXRα improves myocardial glucose tolerance and reduces cardiac hypertrophy in a mouse model of obesity-induced type 2 diabetes.

Aims/hypothesis: Diabetic cardiomyopathy is a myocardial disease triggered by impaired insulin signalling, increased fatty acid uptake and diminished glucose utilisation. Liver X receptors (LXRs) are key transcriptional regulators of metabolic homeostasis. However, their effect in the diabetic heart is largely unknown.

Sigma-1 Agonist Binding in the Aging Rat Brain: a MicroPET Study with [(11)C]SA4503.

Purpose: Sigma-1 receptor ligands modulate the release of several neurotransmitters and intracellular calcium signaling. We examined the binding of a radiolabeled sigma-1 agonist in the aging rat brain with positron emission tomography (PET).

Procedures: Time-dependent uptake of [(11)C]SA4503 was measured in the brain of young (1.