Back

Toward the Clinical Translation of Safe Intravenous Long Circulating Iodinated Lipid Nanoemulsion Contrast Agents for CT Imaging

Attia, M. F.; Marasco, R. N.; Kwain, S.; Foxx, C.; Whitehead, D. C.; Kabanov, A.; Lee, Y. Z.

2024-08-29 bioengineering
10.1101/2024.08.28.610138 bioRxiv
Show abstract

Current clinical small molecule x-ray CT agents are effective but pose risks such as nephrotoxicity, short blood circulation time, limiting scan durations, potential thyroid impact, and immune responses. These challenges drive the development of kidney-safe x-ray nanoparticle (NP)-based contrast agents (CAs), though translation to clinical practice is hindered by chemical complexities and potential toxicity. We have engineered an intravenous, injectable, and safe blood pool NP-based CT CAs at a clinical-equivalent dose of [~]300 mgI/kg ([~]2 mL/kg), ideal for vascular and hepatic imaging which are limited by clinical agents. Our iodinated lipid nanodroplet emulsions (ILNEs) contrast agent offers high x-ray attenuation thus improved contrast enhancement, extended stability, and exceptional batch-to-batch consistency. It also boasts a straightforward and scalable manufacturing process with minimal protein interaction, prolonged blood residency ([~]4h), and hepatic clearance within 3 days, avoiding nephrotoxicity. Studies in vitro, in mice, and 16.6kg porcine animal model studies confirm its safety, cytocompatibility, and absence of tissue damage. Blood, and thyroid-stimulating hormone (TSH) analyses, and kidney and liver function tests, also support further toxicity evaluations for clinical translation.

Matching journals

The top 7 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.