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

Jewell, Adelaide; Williams, Hannah; Hoad, Caroline L.; Gellert, Paul R.; Ashford, Marianne B.; Butler, James; Stolnik, Snow; Scurr, David; Stocks, Michael J.; Marciani, Luca; Gowland, Penny A.; Gershkovich, Pavel

Abstract

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.

Citation

Jewell, A., Williams, H., Hoad, C. L., Gellert, P. R., Ashford, M. B., Butler, J., …Gershkovich, P. (2021). 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. Pharmaceutics, 13(9), Article 1343. https://doi.org/10.3390/pharmaceutics13091343

• Journal Article Type: Article
• Acceptance Date: Aug 25, 2021
• Online Publication Date: Aug 27, 2021
• Publication Date: 2021-09
• Deposit Date: Sep 23, 2021
• Publicly Available Date: Sep 23, 2021
• Journal: Pharmaceutics
• Electronic ISSN: 1999-4923
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 9
• Article Number: 1343
• DOI: https://doi.org/10.3390/pharmaceutics13091343
• Public URL: https://nottingham-repository.worktribe.com/output/6245046
• Publisher URL: https://www.mdpi.com/1999-4923/13/9/1343