Enhanced Local Drug Accumulation via Intra-Arterial Administration of Magnetic Nanoparticles and Hyperthermia Induced Antitumor Effects in a Rat Pancreatic Cancer Model

Wednesday, April 2, 2025

10:30 AM – 10:39 AM CT

Location: Music City Center, 207 CD

Presenting Author(s)

Kentaro Yamada, MD, PhD (he/him/his)

Research Assistant Professor
Oregon Health & Science University, United States

Author/Co-author(s)

KM

Kenkichi Michimoto, MD, PhD (he/him/his)

Postdoctoral Scholar
Dotter Department of Interventional Radiology, Oregon Health & Science University, United States
PS

Prem Singh, PhD

Postdoctoral Scholar
Department of Pharmaceutical Sciences, Oregon State University, United States
TG

Todd Graham, MS

Senior Research Associate
Oregon Health & Science University, United States
AA

Arianna Anoushiravani, BS

Rsearch fellow
Dotter Department of Interventional Radiology, Oregon Health & Science University, United States
YS

Yadong Shi, MD

Rsearch fellow
Dotter Department of Interventional Radiology, Oregon Health & Science University, United States
OT

Oleh Taratula, PhD

Associate Professor
Oregon State University, United States
Khashayar Farsad, MD, PhD (he/him/his)

Professor
Oregon Health and Science University, United States

Purpose: To investigate whether selective intra-arterial administration (IA) of cobalt-doped iron oxide nanoparticles (IONPs) enhances drug accumulation in pancreatic cancer compared to systemic IV in a rat orthotopic pancreatic cancer model. Additionally, to assess the anti-tumor efficacy of hyperthermia induced by an alternating magnetic field (AMF) following IONPs IA.

Materials and Methods:

IONPs with a fluorescent dye were conjugated with an LHRH receptor-targeting peptide to improve tumor accumulation. Based on a previous report {1}, an orthotopic pancreatic cancer model was created using DSL6A/C1 rat pancreatic cancer cells; animals with tumors over 10 mm were enrolled. For the biodistribution study, the IV group received 4 mg Fe/kg (n=4) based on the prior study {2}, the IA group received 10% or 20% of IV dose via the splenic a. (n=5) followed by embolization with gelatin sponge. Organs were harvested at 24 hrs (IV group) and 1 hr (IA group) post-administration. Near-infrared (NIR) imaging measured fluorescence signal intensity (SI); organ-to-tumor SI ratios were compared. For therapeutic evaluation, the control group received IONPs IA and TAE; the treatment group additionally received 30 mins AMF (235 kHz, 27.1 kA m-1). Tumor volumes were measured at days 7, 14, and 21 post-treatment, and changes relative to pre-treatment were compared.

Results:

Organ-to-tumor NIR signal ratios in the brain, lungs, heart, liver, and kidneys were significantly lower in the IA group compared to the IV group (p < 0.05 each), indicating reduced systemic exposure of IONPs with IA; no significant difference was observed in the spleen. Despite receiving only 10% or 20% of the IV dose, the tumor SI tended to be higher in the IA group, although it was not significant (IA vs IV, median SI, 12.0 vs 5.67, p = 0.064). The AMF group showed tumor shrinkage or suppressed growth rates compared to consistent tumor growth in the control group (Table). One animal was lost during the follow-up. Residual accumulation of IONPs in tumor tissue was confirmed via NIR imaging after the 21-day follow-up.

Conclusion:

In a rat pancreatic cancer model, IA administration of IONPs at 10% or 20% of the IV dose achieved local drug accumulation comparable to that of IV administration. The combination of IONPs and AMF-induced hyperthermia demonstrated significant anti-tumor effects.