Aydin Eresen, PhD (he/him/his)
University of California, Irvine
Disclosure(s): No financial relationships to disclose
We investigated the hypothesis that MRI can monitor transcatheter intraportal vein (IPV) delivery of clinically applicable Heparin-Protamine-Ferumoxytol (HPF) nanocomplex-labeled natural killer (NK) cells to the liver tumor in a rat model of liver tumor. Our study aims to test transcatheter intraportal vein (IPV) infusion of natural killer (NK) cells for liver tumor adoptive transfer immunotherapy in a rat model of liver tumor.
Materials and Methods:
NK cell line NK-92MI was cultured and labeled with FDA-approved heparin-protamine-ferumoxytol (HPF) nanocomplexes. Twenty-four male Sprague–Dawley rats implanted N1S1 tumors. Liver tumor rat models underwent catheterization for IPV infusion of HPF-labeled NK cells (n = 12) and intravenous (IV) injection (n = 12). MRI measurements within the tumor and adjacent liver tissues were compared pre- and post-NK cell infusion. Histology studies were used to identify NK cells in the target tumors.
For IPV infusion, a significant difference in R2* values was found before and 30 min after NK cell infusion within liver tissues surrounding the tumors (pre-infusion vs. 30-min post-infusion; 75.12 ± 9.18 s-1 vs. 143.5 ±13.14 s-1; p < 0.001), but no significant difference was found in the tumor nodules at this earlier 30-min follow-up period (p > 0.05). A significant difference in R2* values was found for the tumor tissues at the 12 h post-infusion follow-up interval (30-min post-infusion vs. 12 h post-infusion p < 0.001). Moreover, there were significant differences (in both tumors and surrounding liver tissues) between IV. and IPV groups at 12 h post-infusion (all p < 0.05). Histological results confirmed MRI findings.
Transcatheter IPV infusion permitted selective delivery of NK cells to liver tissues, and MRI allowed tracking NK cell biodistributions within the tumors.