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

Sijbesma, J. W. A.; Zhou, Xiaochi; García, David Vállez; Houwertjes, M. C.; Doorduin, Janine; Kwizera, Chantal; Maas, Bram; Meerlo, Peter; Dierckx, Rudi; Slart, Riemer H. J. A.; Elsinga, Philip H.; Waarde, Aren van

doi:10.1007/s11307-016-0954-9

Cited by 8 publications

(6 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Before each scan, a cannula was placed in a side branch of the femoral artery for blood sampling during the scan. 30 During this surgery, the rats were also under anesthesia for about 30 min. Anesthesia for surgery and PET scanning lasted 86−120 min.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, in “Anesthesia-exposed” and “Retest” PETs, the animals were anesthetized twice, and in the “Test” animals were anesthetized only once. Before each scan, a cannula was placed in a side branch of the femoral artery for blood sampling during the scan . During this surgery, the rats were also under anesthesia for about 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…IBM SPSS Statistics version 23 (Armonk, NY) was used. ICC values between 0 and 0.2, 0.3 and 0.4, 0.5 and 0.6, 0.7 and 0.8, and 0.9 and 1 are categorized as slight, fair, moderate, substantial and almost perfect agreement, respectively. , …”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Test–Retest Repeatability of [¹⁸F]MC225-PET in Rodents: A Tracer for Imaging of P-gp Function

García-Varela

García

Rodríguez-Pérez

et al. 2020

ACS Chem. Neurosci.

Self Cite

View full text Add to dashboard Cite

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 [ 18 F]MC225 PET scans. Thus, dynamic PET scans with blood sampling were conducted in 13 Wistar rats. Seven animals were exposed to isoflurane anesthesia 1 week before the PET scan ("Anesthesiaexposed" PET). A second group of six animals was used to evaluate the reproducibility of measurements of P-gp function at the blood−brain barrier (BBB) with [ 18 F]MC225. In this group, two PET scans were made with a 1 week interval ("Test" and "Retest" PET). Pharmacokinetic parameters were calculated using compartmental models and metabolite-corrected plasma as an input function. "Anesthesia-exposed" animals showed a 28% decrease in whole-brain volume of distribution (V T ) (p < 0.001) compared to "Test", where the animals were not previously anesthetized. The V T at "Retest" also decreased (19%) compared to "Test" (p < 0.001). The k 2 values in whole-brain were significantly increased by 18% in "Anesthesia-exposed" (p = 0.005) and by 15% in "Retest" (p = 0.008) compared to "Test". However, no significant differences were found in the influx rate constant K 1 , which is considered as the best parameter to measure the P-gp function. Moreover, Western Blot analysis did not find significant differences in the P-gp expression of animals not pre-exposed to anesthesia ("Test") or pre-exposed animals ("Retest"). To conclude, anesthesia may affect the brain distribution of [ 18 F]MC225 but it does not affect the P-gp expression or function.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Test–Retest Repeatability of [¹⁸F]MC225-PET in Rodents: A Tracer for Imaging of P-gp Function

García-Varela

García

Rodríguez-Pérez

et al. 2020

ACS Chem. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the group that was scanned with [ 11 C]GSK-189254, a second cannula was placed in a side branch of the femoral artery for collection of arterial blood samples, using a previously published procedure that allows longitudinal PET studies with repeated arterial cannulation. 45 Rats were positioned with the brain in the field of view and, prior to each emission scan, a transmission scan was made using a 57 Co point source, for attenuation and scatter correction of the final PET images. The body temperature of the rats was continuously recorded, using a rectal PTC thermometer (PicoTechnology, St. Neots, U.K.).…”

Section: Materials and Methodsmentioning

confidence: 99%

Binding of the Dual-Action Anti-Parkinsonian Drug AG-0029 to Dopamine D₂ and Histamine H₃ Receptors: A PET Study in Healthy Rats

et al. 2022

Self Cite

View full text Add to dashboard Cite

Introduction : 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 2 /D 3 agonist/H 3 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). Methods : Healthy male Wistar rats were scanned with a small-animal PET camera, using either the dopamine D 2 /D 3 receptor ligand [ 11 C]raclopride or the histamine H 3 receptor ligand [ 11 C]GSK-189254, before and after treatment with an intravenous, acute, single dose of AG-0029. Dynamic [ 11 C]raclopride PET data (60 min duration) were analyzed using the simplified reference tissue model 2 (SRTM2) with cerebellum as reference tissue and the nondisplaceable binding potential as the outcome parameter. Data from dynamic [ 11 C]GSK-189254 scans (60 min duration) with arterial blood sampling were analyzed using Logan graphical analysis with the volume of distribution ( V T ) as the outcome parameter. Receptor occupancy was estimated using a Lassen plot. Results : Dopamine D 2/3 receptor occupancies in the striatum were 22.6 ± 18.0 and 84.0 ± 3.5% (mean ± SD) after administration of 0.1 and 1 mg/kg AG-0029, respectively. In several brain regions, the V T values of [ 11 C]GSK-189254 were significantly reduced after pretreatment of rats with 1 or 10 mg/kg AG-0029. The H 3 receptor occupancies were 11.9 ± 8.5 and 40.3 ± 11.3% for the 1 and 10 mg/kg doses of AG-0029, respectively. Conclusions : Target engagement of AG-0029 as an agonist at dopamine D 2 /D 3 receptors and an antagonist at histamine H 3 receptors could be demonstrated in the rat brain with [ 11 C]raclopride and [ 11 C]GSK-189254 PET, respectively. The measured occupancy values reflect the previously reported high (subnanomolar) affinity of AG-0029 to D 2 /D 3 and moderate (submicromolar) affinity to H 3 receptors.

show abstract

“…Hence, higher numbers of animals are needed to gain statistically reliable results. To assess the influence of these limitations on the estimation of quantitative binding values and to determine the optimal quantification approach for a given PET tracer in small laboratory animals, test-retest experiments have been performed for several CNS PET ligands [11][12][13][75][76][77][78][79][80][81][82][83]. In addition, physiological parameters can also vary within one animal at two different scan time points and may influence receptor availability, limiting the ability of PET to detect differences in an interventional study where a baseline and a treatment scan are compared.…”

Section: Data Acquisition Corrections and Reconstructionmentioning

confidence: 99%

Quantitative Rodent Brain Receptor Imaging

et al. 2019

View full text Add to dashboard Cite

Positron emission tomography (PET) is a non-invasive imaging technology employed to describe metabolic, physiological, and biochemical processes in vivo. These include receptor availability, metabolic changes, neurotransmitter release, and alterations of gene expression in the brain. Since the introduction of dedicated small-animal PET systems along with the development of many novel PET imaging probes, the number of PET studies using rats and mice in basic biomedical research tremendously increased over the last decade. This article reviews challenges and advances of quantitative rodent brain imaging to make the readers aware of its physical limitations, as well as to inspire them for its potential applications in preclinical research. In the first section, we briefly discuss the limitations of small-animal PET systems in terms of spatial resolution and sensitivity and point to possible improvements in detector development. In addition, different acquisition and post-processing methods used in rodent PET studies are summarized. We further discuss factors influencing the test-retest variability in small-animal PET studies, e.g., different receptor quantification methodologies which have been mainly translated from human to rodent receptor studies to determine the binding potential and changes of receptor availability and radioligand affinity. We further review different kinetic modeling approaches to obtain quantitative binding data in rodents and PET studies focusing on the quantification of endogenous neurotransmitter release using pharmacological interventions. While several studies have focused on the dopamine system due to the availability of several PET tracers which are sensitive to dopamine release, other neurotransmitter systems have become more and more into focus and are described in this review, as well. We further provide an overview of latest genome engineering technologies, including the CRISPR/Cas9 and DREADD systems that may advance our understanding of brain disorders and function and how imaging has been successfully applied to animal models of human brain disorders. Finally, we review the strengths and opportunities of simultaneous PET/magnetic resonance imaging systems to study drug-receptor interactions and challenges for the translation of PET results from bench to bedside.aligned to a standard reference space for several PET radioligands [63,64]. This enables the use of an automatic normalization and the application of predefined VOIs, minimizing the user-dependent variability. This is particularly important in small-animal PET brain studies, if a voxelbased analysis is performed and small deviations from the standard space will largely impact the results.Quantification Accuracy: Partial-Volume Effect, Spillover, Mass Effect, and Data Reproducibility

show abstract

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

Cited by 8 publications

References 20 publications

Test–Retest Repeatability of [¹⁸F]MC225-PET in Rodents: A Tracer for Imaging of P-gp Function

Test–Retest Repeatability of [¹⁸F]MC225-PET in Rodents: A Tracer for Imaging of P-gp Function

Binding of the Dual-Action Anti-Parkinsonian Drug AG-0029 to Dopamine D₂ and Histamine H₃ Receptors: A PET Study in Healthy Rats

Quantitative Rodent Brain Receptor Imaging

Contact Info

Product

Resources

About

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

Cited by 8 publications

References 20 publications

Test–Retest Repeatability of [18F]MC225-PET in Rodents: A Tracer for Imaging of P-gp Function

Test–Retest Repeatability of [18F]MC225-PET in Rodents: A Tracer for Imaging of P-gp Function

Binding of the Dual-Action Anti-Parkinsonian Drug AG-0029 to Dopamine D2 and Histamine H3 Receptors: A PET Study in Healthy Rats

Quantitative Rodent Brain Receptor Imaging

Contact Info

Product

Resources

About

Test–Retest Repeatability of [¹⁸F]MC225-PET in Rodents: A Tracer for Imaging of P-gp Function

Test–Retest Repeatability of [¹⁸F]MC225-PET in Rodents: A Tracer for Imaging of P-gp Function

Binding of the Dual-Action Anti-Parkinsonian Drug AG-0029 to Dopamine D₂ and Histamine H₃ Receptors: A PET Study in Healthy Rats