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[¹⁸F]BODIPY-triglyceride-containing chylomicron-like particles as an imaging agent for brown adipose tissue in vivo.

ABSTRACT: Brown adipose tissue (BAT) is present in human adults and the current gold standard to visualize and quantify BAT is [¹⁸F]FDG PET-CT. However, this method fails to detect BAT under insulin-resistant conditions associated with ageing and weight gain, such as type 2 diabetes. The aim of this study was to develop a novel triglyceride-based tracer for BAT. For this purpose we designed a dual-modal fluorescent/PET fatty acid tracer based on commercially available BODIPY-FL-C₁₆, which can be esterified to its correspondent triglyceride, radiolabeled and incorporated into pre-synthesized chylomicron-like particles. BODIPY-FL-C₁₆ was coupled to 1,2-diolein with a subsequent radiolabeling step resulting in [¹⁸F]BODIPY-C₁₆-triglyceride that was incorporated into chylomicron-like particles. Various quality control steps using fluorescent and radioactive methods were conducted before BAT visualization was tested in mice. Triglyceride synthesis, radiolabeling and subsequent incorporation into chylomicron-like particles was carried out in decent yields. This radiotracer appeared able to visualize BAT in vivo, and the uptake of the radiotracer was stimulated by cold exposure. The here reported method can be used to incorporate radiolabeled triglycerides into pre-synthesized chylomicron-like particles. Our approach is feasible to visualize and quantify the uptake of triglyceride-derived fatty acids by BAT.

SUBMITTER: Paulus A

PROVIDER: S-EPMC6389948 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBrown adipose tissue (BAT) is a thermogenic tissue which can generate heat in response to mild cold exposure. As it constitutes a promising target in the fight against obesity, we need reliable techniques to quantify its activity in response to therapeutic interventions. The current standard for the quantification of BAT activity is [18F]FDG PET/CT. Various sequences in magnetic resonance imaging (MRI), including those measuring its relative fat content (fat fraction), have been proposed and evaluated in small proof-of-principle studies, showing diverging results. Here, we systematically compare the predictive value of adipose tissue fat fraction measured by MRI to the results of [18F]FDG PET/CT.MethodsWe analyzed the diagnostic reliability of MRI measured fat fraction (FF) for the estimation of human BAT activity in two cohorts of healthy volunteers participating in two prospective clinical trials (NCT03189511, NCT03269747). In both cohorts, BAT activity was stimulated by mild cold exposure. In cohort 1, we performed [18F]FDG PET/MRI; in cohort 2, we used [18F]FDG PET/CT followed by MRI. Fat fraction was determined by 2-point Dixon and 6-point Dixon measurement, respectively. Fat fraction values were compared to SUVmean in the corresponding tissue depot by simple linear regression.ResultsIn total, 33 male participants with a mean age of 23.9 years and a mean BMI of 22.8 kg/m2 were recruited. In 32 participants, active BAT was visible. On an intra-individual level, FF was significantly lower in high-SUV areas compared to low-SUV areas (cohort 1: p < 0.0001 and cohort 2: p = 0.0002). The FF of the supraclavicular adipose tissue depot was inversely related to its metabolic activity (SUVmean) in both cohorts (cohort 1: R2 = 0.18, p = 0.09 and cohort 2: R2 = 0.42, p = 0.009).ConclusionMRI FF explains only about 40% of the variation in BAT glucose uptake. Thus, it can currently not be used to substitute [18F] FDG PET-based imaging for quantification of BAT activity.Trial registrationClinicalTrials.gov. NCT03189511 , registered on June 17, 2017, actual study start date was on May 31, 2017, retrospectively registered. NCT03269747 , registered on September 01, 2017.

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[¹⁸F]BODIPY-triglyceride-containing chylomicron-like particles as an imaging agent for brown adipose tissue in vivo.

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OmicsDI is part of the ELIXIR infrastructure

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[18F]BODIPY-triglyceride-containing chylomicron-like particles as an imaging agent for brown adipose tissue in vivo.

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OmicsDI is part of the ELIXIR infrastructure

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[¹⁸F]BODIPY-triglyceride-containing chylomicron-like particles as an imaging agent for brown adipose tissue in vivo.