Assessing Lymphatic Uptake of Lipids Using Magnetic Resonance Imaging: A Feasibility Study in Healthy Human Volunteers with Potential Application for Tracking Lymph Node Delivery of Drugs and Formulation Excipients
Adelaide Jewell,
Hannah Williams,
Caroline L. Hoad,
Paul R. Gellert,
Marianne B. Ashford,
James Butler,
Snow Stolnik,
David Scurr,
Michael J. Stocks,
Luca Marciani,
Penny A. Gowland,
Pavel Gershkovich
Affiliations
Adelaide Jewell
School of Pharmacy, University of Nottingham, Nottingham NG7 2QL, UK
Hannah Williams
Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2QX, UK
Caroline L. Hoad
Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2QX, UK
Paul R. Gellert
Advanced Drug Delivery Pharmaceutical Sciences, R&D, AstraZeneca, Macclesfield SK10 2NA, UK
Marianne B. Ashford
Advanced Drug Delivery Pharmaceutical Sciences, R&D, AstraZeneca, Macclesfield SK10 2NA, UK
James Butler
GlaxoSmithKline Research and Development, Ware, Hertfordshire SG12 0DP, UK
Snow Stolnik
School of Pharmacy, University of Nottingham, Nottingham NG7 2QL, UK
David Scurr
School of Pharmacy, University of Nottingham, Nottingham NG7 2QL, UK
Michael J. Stocks
School of Pharmacy, University of Nottingham, Nottingham NG7 2QL, UK
Luca Marciani
National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK
Penny A. Gowland
Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2QX, UK
Pavel Gershkovich
School of Pharmacy, University of Nottingham, Nottingham NG7 2QL, UK
Dietary lipids and some pharmaceutical lipid excipients can facilitate the targeted delivery of drugs to the intestinal lymphatics. Here, the feasibility of magnetic resonance imaging (MRI) for imaging lipid uptake into the intestinal lymphatics was assessed, shedding light on which lymph nodes can be targeted using this approach. Three healthy male volunteers were scanned at 3.0 T at baseline, 120, 180, 240, and 300 min post high-fat meal. A sagittal multi-slice image was acquired using a diffusion-weighted whole-body imaging sequence with background suppression (DWIBS) (pre inversion TI = 260 ms). Changes in area, major, and minor axis length were compared at each time point. Apparent diffusion coefficient (ADC) was calculated (b = 0 and 600 s/mm2) across eight slices. An average of 22 nodes could be visualised across all time points. ADC increased at 120 and 180 min compared to the baseline in all three participants by an average of 9.2% and 6.8%, respectively. In two participants, mean node area and major axis lengths increased at 120 and 180 min relative to the baseline. In conclusion, the method described shows potential for repeated lymph node measurements and the tracking of lipid uptake into the lymphatics. Further studies should focus on methodology optimisation in a larger cohort.