MRI Monitoring Transcatheter Intraportal Vein Delivery of Clinically-Applicable-Magnetic Labeled Natural Killer Cells for Liver Tumor Adoptive immunotherapy

Wednesday, March 8, 2023

3:54 PM – 4:03 PM

Location: Phoenix Convention Center, 222AB

Presenting Author(s)

Aydin Eresen, PhD (he/him/his)

Postdoctoral Fellow
University of California, Irvine

Disclosure(s): No financial relationships to disclose

Author/Co-author(s)

ZZ

Zigeng Zhang, MD

Postdoctoral Fellow
University of California, Irvine
Zeyang Yu, MS (he/him/his)

Research volunteer (master student)
University of Washington
Nadine Abi-Jaoudeh, MD, FSIR

Professor of Radiology
University of California
Farouk Nouizi, PhD

Assistant Researcher
Radiological Sciences - UCI
VY

Vahid Yaghmai, n/a

Chairman of Radiology
University of California, Irvine
ZZ

Zhuoli Zhang, PhD

Professor
University of California, Irvine

Disclosure(s):

Aydin Eresen, PhD: No financial relationships to disclose

Zigeng Zhang, MD: No financial relationships to disclose

Zeyang Yu, MS: No financial relationships to disclose

Nadine Abi-Jaoudeh, MD, FSIR: Angiodynamics Inc: Contracted Research (Ongoing); AstraZeneca: Consultant (Ongoing); BlackSwan Vascular Inc: Contracted Research (Terminated, November 7, 2022); Bruin Biosciences Inc.: Ownership Interest (Ongoing); Eisai Co., Ltd: Advisory Committee or Review Panel Member (Terminated, April 15, 2021); Genentech F. Hoffmann-La Roche Ltd: Consultant (Ongoing); Guerbet SA: Research Grant Recipient (Ongoing); Histosonics Inc.: Data safety Monitoring Board (Ongoing); Innova Vascular Inc: Advisory Committee or Review Panel Member (Ongoing); Instylla HES Inc: Contracted Research (Ongoing); Johnson and Johnson: Consultant (Ongoing); Lynx Group LLC: Advisory Committee or Review Panel Member (Terminated, January 27, 2022); Medtronic Inc: Advisory Committee or Review Panel Member (Terminated, April 30, 2021); Pfizer Inc: Advisory Committee or Review Panel Member (Terminated, October 15, 2021); Philips Medical Systems Inc Koninklijke NV: Research Grant Recipient (Ongoing); QED Therapeutics Inc: Advisory Committee or Review Panel Member (Terminated, February 1, 2021); Sirtex Medical Ltd: Contracted Research (Ongoing); Teclison Limited (PI): Research Grant Recipient (Ongoing)

Farouk Nouizi, PhD: No financial relationships to disclose

Purpose:

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.

Results:

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.

Conclusion:

Transcatheter IPV infusion permitted selective delivery of NK cells to liver tissues, and MRI allowed tracking NK cell biodistributions within the tumors.