Intra-Arterial Drug Delivery of Both a Small and Large Molecule Theranostic Radiotracer Probe into an Orthotopic OncoPIG Liver Tumor Model After Pseudovascular Isolation.

Abstract

Purpose: Directed therapies employing small (SM) and large (LM) molecule drugs to target tumor antigens are used for treatment. Theranostics radiolabels them for imaging and radiation treatment. Poor radiopharmaceutical kinetics, prolonged circulating times, and high nontarget radiation to normal tissues after intravenous (i.v) injection limits translation. Intra-arterial (i.a.) procedures locally concentrate nonspecific chemotherapies or radiation to treat hepatic tumors (HT). Pseudovascular isolation (PVI), embolizes the HT arterioles, blocking efferent flow into capillaries isolating the HT from the systemic vasculature maximizing uptake to provide curative tumor specific absorbed radiation.

Methods: [¹⁸F]Fluorodeoxyglucose (FDG) SM and ^99mTc-labeled macroaggregated albumin (MAA) LM surrogates were used to assess biodistribution in a porcine HT. Injected dose per gram (%ID/g) of the tracers obtained from 1 to 120 min after control (i.v) and experimental i.a. infusion with PVI.

Results: SM drug delivered to HT was 290-366% greater for PVI vs. i.v (60 min %ID/g 31.26 ± 2.55 vs. 8.83 ± 0.55, p = 0.033; 120 min 29.28 ± 1.44 vs. 8.94 ± 0.96, p = 0.145). Mean HT uptake of LM with PVI was up to 760% greater than i.v. without washout (60 min %ID/g 80.01 ± 2.87 vs. 10.61 ± 0.96 p = 0.001; 81.72 ± 3.0 vs. 11.98 ± 0.3 p = 0.001 at 120 min).

Conclusion: PVI significantly increases the concentration of both SM and LM drugs within a HT compared to i.v. infusion. PVI with tumor specific drugs offers an opportunity to locally cure HT using a drug that specifically targets tumor antigens.