Dataset Information

Effect of 26 Weeks of Liraglutide Treatment on Coronary Artery Inflammation in Type 2 Diabetes Quantified by [⁶⁴Cu]Cu-DOTATATE PET/CT: Results from the LIRAFLAME Trial.

ABSTRACT:

Background

Quantification of coronary artery inflammation and atherosclerosis remains a challenge in high-risk individuals. In this study we sought to investigate if the glucagon like peptide-1 receptor agonist liraglutide has a direct anti-inflammatory effect in the coronary arteries using positron emission tomography (PET) with a radioactive tracer targeting activated macrophages in the vessel-wall.

Methods

Thirty randomly selected participants with type 2 diabetes from the placebo-controlled trial LIRAFLAME were enrolled in this sub-study. Participants were, prior to enrollment in this sub-study, randomized to either treatment with daily liraglutide (n=15) or placebo (n=15). Both groups underwent a combined [⁶⁴Cu]Cu-DOTATATE positron emission tomography and computed tomography scan of the heart at baseline and after 26 weeks of treatment. Coronary artery uptake of [⁶⁴Cu]Cu-DOTATATE were measured as maximum standardized uptake values (SUV_max); and means of the maximum values (mSUV_max), both values were calculated at the level of each participant and each individual coronary-segment.

Results

SUV_max and mSUV_max values decreased significantly in the liraglutide group both at the participant level (SUV_max: p=0.013; mSUV_max: p=0.004) and at the coronary-segment level (SUV_max: p=0.001; mSUV_max: p<0.0001). No change was observed in the placebo group neither at the participant level (SUV_max: p=0.69; mSUV_max: p=0.67) or at the coronary-segment level (SUV_max: p=0.49; mSUV_max: p=0.30). When comparing the mean change in uptake values between the two groups at both the participant level (SUV_max: p=0.076; mSUV_max: p=0.077) and the coronary segment level (SUV_max: p=0.13; mSUV_max: p=0.11) a borderline significant difference was observed. Baseline SUV_max [⁶⁴Cu]Cu-DOTATATE uptake values showed a weak positive correlation with the inflammatory biomarker high-sensitivity c-reactive protein (τ =0.26, p=0.045).

Conclusion

Liraglutide treatment for 26-weeks caused a significant reduction in [⁶⁴Cu]Cu-DOTATATE uptake in the coronary arteries whereas this was not seen in the placebo treated group. In addition, [⁶⁴Cu]Cu-DOTATATE PET/CT as a marker of coronary inflammation correlated with the systemic inflammation marker hs-CRP.

SUBMITTER: Jensen JK

PROVIDER: S-EPMC8669791 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Effect of 26 Weeks of Liraglutide Treatment on Coronary Artery Inflammation in Type 2 Diabetes Quantified by [<sup>64</sup>Cu]Cu-DOTATATE PET/CT: Results from the LIRAFLAME Trial.

Jensen Jacob K JK Zobel Emilie H EH von Scholten Bernt J BJ Rotbain Curovic Viktor V Hansen Tine W TW Rossing Peter P Kjaer Andreas A Ripa Rasmus S RS

Frontiers in endocrinology 20211130

<h4>Background</h4>Quantification of coronary artery inflammation and atherosclerosis remains a challenge in high-risk individuals. In this study we sought to investigate if the glucagon like peptide-1 receptor agonist liraglutide has a direct anti-inflammatory effect in the coronary arteries using positron emission tomography (PET) with a radioactive tracer targeting activated macrophages in the vessel-wall.<h4>Methods</h4>Thirty randomly selected participants with type 2 diabetes from the plac ...[more]

PMID: 34917038

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Project description:Current noninvasive imaging methods for monitoring immune response were largely developed for interrogation of the local reaction. This study developed the radiotracer 64Cu-labeled anti-CD11b (64Cu-αCD11b) for longitudinal assessment of local and systemic immune response involving mobilization of CD11b+ myeloid cells by small-animal PET/CT. Methods: Acute or chronic inflammation in the ears of BALB/c mice was induced by 12-o-tetradecanoylphorbol-13-acetate. Acute lung inflammation was induced by intratracheal lipopolysaccharide inoculation. αCD11b was conjugated with p-SCN-Bn-DOTA followed by labeling with 64Cu. PET/CT and biodistribution were evaluated at different times after intravenous injection of 64Cu-αCD11b. Cell populations from bone marrow (BM) and spleen were analyzed by flow cytometry. Results: 64Cu-αCD11b was primarily taken up by BM and spleen in control mice. In comparison, 64Cu-αCD11b uptake was significantly reduced in the BM and spleen of CD11b-knockout mice, indicating that 64Cu-αCD11b selectively homed to CD11b+ myeloid cells in vivo. In mice with ear inflammation, for the local inflammatory response, 64Cu-αCD11b PET/CT revealed significantly higher 64Cu-αCD11b uptake in the inflamed ears in the acute inflammation phase than the chronic phase, consistent with markedly increased infiltration of CD11b+ cells into the inflammatory lesions at the acute phase. Moreover, imaging of 64Cu-αCD11b also showed the difference in mouse systemic response for different inflammatory stages. Compared with uptake in control mice, BM 64Cu-αCD11b uptake in mice with ear inflammation was significantly lower in the acute phase and higher in the chronic phase, reflecting an initial mobilization of CD11b+ cells from the BM to the inflammatory foci followed by a compensatory regeneration of CD11b+ myeloid cells in the BM. Similarly, in mice with lung inflammation, 64Cu-αCD11b PET/CT readily detected acute lung inflammation and recruitment of CD11b+ myeloid cells from the BM. Immunohistochemistry staining and flow cytometry results confirmed the noninvasive imaging of PET/CT. Conclusion: 64Cu-αCD11b PET/CT successfully tracked ear and pulmonary inflammation in mice and differentiated acute from chronic inflammation at the local and systemic levels. 64Cu-αCD11b PET/CT is a robust quantitative method for imaging of local and systemic immune responses.

Project description:PurposeCopper is essential for enzymatic processes throughout the body. [64Cu]copper (64Cu) positron emission tomography (PET) has been investigated as a diagnostic tool for certain malignancies, but has not yet been used to study copper homeostasis in humans. In this study, we determined the hepatic removal kinetics, biodistribution and radiation dosimetry of 64Cu in healthy humans by both intravenous and oral administration.MethodsSix healthy participants underwent PET/CT studies with intravenous or oral administration of 64Cu. A 90 min dynamic PET/CT scan of the liver was followed by three whole-body PET/CT scans at 1.5, 6, and 20 h after tracer administration. PET data were used for estimation of hepatic kinetics, biodistribution, effective doses, and absorbed doses for critical organs.ResultsAfter intravenous administration, 64Cu uptake was highest in the liver, intestinal walls and pancreas; the gender-averaged effective dose was 62 ± 5 μSv/MBq (mean ± SD). After oral administration, 64Cu was almost exclusively taken up by the liver while leaving a significant amount of radiotracer in the gastrointestinal lumen, resulting in an effective dose of 113 ± 1 μSv/MBq. Excretion of 64Cu in urine and faeces after intravenous administration was negligible. Hepatic removal kinetics showed that the clearance of 64Cu from blood was 0.10 ± 0.02 mL blood/min/mL liver tissue, and the rate constant for excretion into bile or blood was 0.003 ± 0.002 min- 1.Conclusion64Cu biodistribution and radiation dosimetry are influenced by the manner of tracer administration with high uptake by the liver, intestinal walls, and pancreas after intravenous administration, while after oral administration, 64Cu is rapidly absorbed from the gastrointestinal tract and deposited primarily in the liver. Administration of 50 MBq 64Cu yielded images of high quality for both administration forms with radiation doses of approximately 3.1 and 5.7 mSv, respectively, allowing for sequential studies in humans.Trial registration numberEudraCT no. 2016-001975-59. Registration date: 19/09/2016.

Dataset Information

Effect of 26 Weeks of Liraglutide Treatment on Coronary Artery Inflammation in Type 2 Diabetes Quantified by [⁶⁴Cu]Cu-DOTATATE PET/CT: Results from the LIRAFLAME Trial.

Background

Methods

Results

Conclusion

Publications

Effect of 26 Weeks of Liraglutide Treatment on Coronary Artery Inflammation in Type 2 Diabetes Quantified by [<sup>64</sup>Cu]Cu-DOTATATE PET/CT: Results from the LIRAFLAME Trial.

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Dataset Information

Effect of 26 Weeks of Liraglutide Treatment on Coronary Artery Inflammation in Type 2 Diabetes Quantified by [64Cu]Cu-DOTATATE PET/CT: Results from the LIRAFLAME Trial.

Background

Methods

Results

Conclusion

Publications

Effect of 26 Weeks of Liraglutide Treatment on Coronary Artery Inflammation in Type 2 Diabetes Quantified by [<sup>64</sup>Cu]Cu-DOTATATE PET/CT: Results from the LIRAFLAME Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Effect of 26 Weeks of Liraglutide Treatment on Coronary Artery Inflammation in Type 2 Diabetes Quantified by [⁶⁴Cu]Cu-DOTATATE PET/CT: Results from the LIRAFLAME Trial.