Abstract
Purpose In pre-clinical studies, super-paramagnetic iron oxide nanoparticles (SPIOs) have shown promise as drug delivery vehicles for hepatocellular carcinoma (HCC). A major limitation of conventional intravenous (IV) administration of SPIOs is deposition in the reticuloendothelial system instead of the target tumor. Local image-guided delivery might be one approach to overcome this limitation and potentially increase efficacy. We aimed to test the hypothesis that ultrasound-guided intratumoral (IT) injection of SPIOs increases uptake and offers more uniform distribution within target tumors compared to IV injection. Materials and Methods We induced HCC tumors using the MCA-RH7777 cell line in 12 Sprague-Dawley rats. After 2 weeks, 7T MRI scans (ClinScan, Bruker) were acquired to verify tumor growth and measure baseline R2*. Rats were randomly assigned to two groups to receive doxorubicin-loaded SPIOs (6 mg/mL) either IV (n=6) or IT (n=6). IT injection was performed percutaneously under ultrasound guidance via a single 30-G needle into multiple regions of the tumor. In all rats, we acquired post-treatment MRI scans 4 hr after injections to measure post-treatment R2* values. ΔR2* was measured as an imaging surrogate for nanoparticle concentration. We compared IV and IT delivery using two separate outcome measures: a) SPIO uptake using a 2-sample T-test and b) SPIO distribution on a pixel-by-pixel basis using Levene's Test, with alpha = 0.05. Results ΔR2* for the IV injected group was 18.9 ± 21.4 s-1 (mean ± SD). ΔR2* for the IT injected group was 46.9 ± 20.4 s-1. SPIO uptake after IT injections was significantly higher than after IV injections (p Conclusion Image-guided IT injection significantly improves uptake of therapeutic nanoparticles into liver tumors, although with more variable uptake distribution, compared to standard IV delivery. Direct IT injections may thus offer less systemic exposure than IV delivery and serve as a successful local method to deliver nanotherapies. Future studies should explore IT methods that can reduce variability of SPIO distribution.
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