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Quantification of Lipoprotein Uptake in Vivo Using Magnetic Particle Imaging and Spectroscopy

Hildebrand, S; Löwa, N; Paysen, H; Fratila, RM; Reverte-Salisa, L; Trakoolwilaiwan, T; Niu, Z; ... Pfeifer, A; + view all (2021) Quantification of Lipoprotein Uptake in Vivo Using Magnetic Particle Imaging and Spectroscopy. ACS Nano , 15 (1) pp. 434-446. 10.1021/acsnano.0c03229. Green open access

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Abstract

Lipids are a major source of energy for most tissues, and lipid uptake and storage is therefore crucial for energy homeostasis. So far, quantification of lipid uptake in vivo has primarily relied on radioactive isotope labeling, exposing human subjects or experimental animals to ionizing radiation. Here, we describe the quantification of in vivo uptake of chylomicrons, the primary carriers of dietary lipids, in metabolically active tissues using magnetic particle imaging (MPI) and magnetic particle spectroscopy (MPS). We show that loading artificial chylomicrons (ACM) with iron oxide nanoparticles (IONPs) enables rapid and highly sensitive post hoc detection of lipid uptake in situ using MPS. Importantly, by utilizing highly magnetic Zn-doped iron oxide nanoparticles (ZnMNPs), we generated ACM with MPI tracer properties superseding the current gold-standard, Resovist, enabling quantification of lipid uptake from whole-animal scans. We focused on brown adipose tissue (BAT), which dissipates heat and can consume a large part of nutrient lipids, as a model for tightly regulated and inducible lipid uptake. High BAT activity in humans correlates with leanness and improved cardiometabolic health. However, the lack of nonradioactive imaging techniques is an important hurdle for the development of BAT-centered therapies for metabolic diseases such as obesity and type 2 diabetes. Comparison of MPI measurements with iron quantification by inductively coupled plasma mass spectrometry revealed that MPI rivals the performance of this highly sensitive technique. Our results represent radioactivity-free quantification of lipid uptake in metabolically active tissues such as BAT.

Type: Article
Title: Quantification of Lipoprotein Uptake in Vivo Using Magnetic Particle Imaging and Spectroscopy
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acsnano.0c03229
Publisher version: https://doi.org/10.1021/acsnano.0c03229
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: BAT, TRL, brown adipose tissue, chylomicron, lipid uptake, magnetic particle imaging, magnetic particle spectroscopy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy
URI: https://discovery.ucl.ac.uk/id/eprint/10119538
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