Dataset Information

[¹⁸F]MPPF and [¹⁸F]FDG μPET imaging in rats: impact of transport and restraint stress.

ABSTRACT:

Background

Stress exposure can significantly affect serotonergic signaling with a particular impact on 5-HT_1A receptor expression. Positron emission tomography (PET) provides opportunities for molecular imaging of alterations in 5-HT_1A receptor binding following stress exposure. Considering the possible role of 5-HT_1A receptors in stress coping mechanisms, respective imaging approaches are of particular interest.

Material and methods

For twelve consecutive days, Sprague Dawley rats were exposed to daily transport with a 1 h stay in a laboratory or daily transport plus 1 h restraint in a narrow tube. Following, animals were subjected to μPET imaging with 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[¹⁸F]fluoro-benzamidoethylpiperazine ([¹⁸F]MPPF) and 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG). Behavioral and biochemical parameters were analyzed to obtain additional information.

Results

In rats with repeated transport, hippocampal [¹⁸F]MPPF binding exceeded that in the naive group, while no difference in [¹⁸F]FDG uptake was detected between the groups. A transient decline in body weight was observed in rats with transport or combined transport and restraint. Thereby, body weight development correlated with [¹⁸F]MPPF binding.

Conclusions

Mild-to-moderate stress associated with daily transport and exposure to a laboratory environment can trigger significant alterations in hippocampal binding of the 5-HT_1A receptor ligand [¹⁸F]MPPF. This finding indicates that utmost care is necessary to control and report transport and associated handling procedures for animals used in μPET studies analyzing the serotonergic system in order to enhance the robustness of conclusions and allow replicability of findings. In view of earlier studies indicating that an increase in hippocampal 5-HT_1A receptor expression may be associated with a resilience to stress, it would be of interest to further evaluate 5-HT_1A receptor imaging approaches as a candidate biomarker for the vulnerability to stress.

SUBMITTER: Buchecker V

PROVIDER: S-EPMC7524912 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

[<sup>18</sup>F]MPPF and [<sup>18</sup>F]FDG μPET imaging in rats: impact of transport and restraint stress.

Buchecker Verena V Waldron Ann-Marie AM van Dijk R Maarten RM Koska Ines I Brendel Matthias M von Ungern-Sternberg Barbara B Lindner Simon S Gildehaus Franz Josef FJ Ziegler Sibylle S Bartenstein Peter P Potschka Heidrun H

EJNMMI research 20200929 1

<h4>Background</h4>Stress exposure can significantly affect serotonergic signaling with a particular impact on 5-HT<sub>1A</sub> receptor expression. Positron emission tomography (PET) provides opportunities for molecular imaging of alterations in 5-HT<sub>1A</sub> receptor binding following stress exposure. Considering the possible role of 5-HT<sub>1A</sub> receptors in stress coping mechanisms, respective imaging approaches are of particular interest.<h4>Material and methods</h4>For twelve con ...[more]

PMID: 32990819

Similar Datasets

Project description:BackgroundThere is evidence that metabolic disease burden in lymphoma influences patient outcome. However, the impact of disease severity on the cardiovascular system is unknown.ObjectivesThe aim of this study was to examine whether lymphoma is associated with arterial inflammation by investigating the relationship between disease metabolic burden and arterial fluorodeoxyglucose (FDG) uptake.MethodsSixty-two chemotherapy-naïve patients with active Hodgkin's or non-Hodgkin's lymphoma were matched (2:1) to individual control groups of lymphoma patients previously treated and free of active disease. All groups underwent 18F-FDG position emission tomography-computed tomography imaging. Disease severity was quantified by metabolic tumor volume (MTV) and total lesion glycolysis corresponding to standardized uptake values (SUVs) ≥41% or ≥2.5 of the maximum SUV within lymphoma regions, and aortic FDG uptake was quantified through the target-to-background ratio (TBR). Inflammatory and disease severity biomarkers were also measured.ResultsMTV and total lesion glycolysis measurements were significantly correlated with inflammatory and disease biomarkers. Aortic TBR was higher in patients with active non-Hodgkin's lymphoma compared with control subjects (median difference 0.51; 95% confidence interval [CI]: 0.28 to 0.78; p < 0.001). Similarly, patients with active Hodgkin's lymphoma had higher values of aortic TBR compared with control subjects (median difference 0.31; 95% CI: 0.15 to 0.49; p < 0.001). In addition, aortic TBR was modestly increased in patients with stage III to IV disease compared with those with stage I to II disease (median aortic TBR: 2.23 [interquartile range: 2.01 to 2.54] vs. 2.06 [interquartile range: 1.83 to 2.27; p = 0.050). In multivariable analysis, aortic FDG uptake and MTV≥2.5 values were independently associated (β = 0.425; 95% CI: 0.189 to 0.662; p = 0.001; R2 = 0.208), as were aortic FDG uptake and MTV≥41% (β = 0.407; 95% CI: 0.167 to 0.649, p = 0.001; R2 = 0.191).ConclusionsAortic wall FDG uptake is related with disease severity indicative of a possible vascular effect of lymphoma. This work highlights a new potential role of molecular imaging in cardio-oncology for evaluating disease severity and its consequences on the vasculature.

Project description:Multiple myeloma (MM) is a debilitating neoplasm of terminally differentiated plasma B cells that resulted in over 13,000 deaths in 2017 alone. Combination therapies involving melphalan, a small-molecule DNA alkylating agent, are commonly prescribed to patients with relapsed or refractory MM, necessitating the stratification of responding patients to minimize toxicities and improve quality of life. Here, we evaluated the use of 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (18F-FDOPA), a clinically available PET radiotracer with specificity to the L-type amino acid transporter 1 (LAT1), which also mediates melphalan uptake, for imaging melphalan therapy response in a preclinical immunocompetent model of MM. Methods: C57BL/KaLwRij mice were implanted subcutaneously with unilateral murine green fluorescent protein-expressing 5TGM1 tumors and divided into 3 independent groups: untreated, treated beginning week 2 after tumor implantation, and treated beginning week 3 after tumor implantation. The untreated and week 2 treated groups were imaged with preclinical MRI and dynamic 18F-FDG and 18F-FDOPA PET/CT at week 4 on separate, contiguous days, whereas the week 3 treated group was longitudinally imaged weekly for 3 wk. Metabolic tumor volume, total lesion avidity, SUVmax, and total uptake were calculated for both tracers. Immunohistochemistry was performed on representative tissue from all groups for LAT1 and glucose transporter 1 (GLUT1) expression. Results: Melphalan therapy induced a statistically significant reduction in lesion avidity and uptake for both 18F-FDG and 18F-FDOPA. There was no visible effect on GLUT1 expression, but LAT1 density increased in the week 2 treated group. Longitudinal imaging of the week 3 treated group showed variable changes in 18F-FDG and 18F-FDOPA uptake, with an increase in 18F-FDOPA lesion avidity in the second week relative to baseline. LAT1 and GLUT1 surface density in the untreated and week 3 treated groups were qualitatively similar. Conclusion: 18F-FDOPA PET/CT complemented 18F-FDG PET/CT in imaging melphalan therapy response in preclinical extramedullary MM. 18F-FDOPA uptake was linked to LAT1 expression and melphalan response, with longitudinal imaging suggesting stabilization of LAT1 levels and melphalan tumor cytotoxicity. Future work will explore additional MM cell lines with heterogeneous LAT1 expression and response to melphalan therapy.

Dataset Information

[¹⁸F]MPPF and [¹⁸F]FDG μPET imaging in rats: impact of transport and restraint stress.

Background

Material and methods

Results

Conclusions

Publications

[<sup>18</sup>F]MPPF and [<sup>18</sup>F]FDG μPET imaging in rats: impact of transport and restraint stress.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

[18F]MPPF and [18F]FDG μPET imaging in rats: impact of transport and restraint stress.

Background

Material and methods

Results

Conclusions

Publications

[<sup>18</sup>F]MPPF and [<sup>18</sup>F]FDG μPET imaging in rats: impact of transport and restraint stress.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

[¹⁸F]MPPF and [¹⁸F]FDG μPET imaging in rats: impact of transport and restraint stress.