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Updated: Sep 14, 2025
Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma
Published on: August 31, 2022
Intra-Arterial Drug Delivery of Both a Small and Large Molecule Theranostic Radiotracer Probe into an Orthotopic
Samuel L Rice1,2, Fernando Gómez Muñoz1, Jamaal Benjamin2
1Department of Radiology, Netherlands Cancer Institute- Antoni van Leeuwenhoekziekenhuis, Plesmanlaan 121, Amsterdam, 1066 CX Netherlands.
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.
Insights
Pseudovascular isolation (PVI) significantly enhances drug delivery to hepatic tumors (HT) via intra-arterial infusion compared to intravenous injection. This technique maximizes therapeutic agent concentration for potential curative treatments.
Area of Science:
- Oncology
- Radiopharmaceuticals
- Interventional Radiology
Background:
- Directed therapies use small (SM) and large (LM) molecule drugs targeting tumor antigens.
- Theranostics combine imaging and treatment by radiolabeling these drugs.
- Intravenous (i.v.) injection faces limitations like poor kinetics and off-target radiation.
Purpose of the Study:
- To evaluate the efficacy of pseudovascular isolation (PVI) in enhancing drug delivery to hepatic tumors (HT).
- To compare drug uptake in HT using PVI with intra-arterial (i.a.) infusion versus i.v. injection.
Main Methods:
- Utilized [¹⁸F]Fluorodeoxyglucose (FDG) as an SM surrogate and 99mTc-labeled macroaggregated albumin (MAA) as an LM surrogate.
- Assessed biodistribution and injected dose per gram (%ID/g) in a porcine HT model.
- Compared i.v. injection with experimental i.a. infusion utilizing PVI over 120 minutes.
Main Results:
- SM drug delivery to HT was 290-366% greater with PVI compared to i.v. (60 min: 31.26 ± 2.55 vs. 8.83 ± 0.55 %ID/g).
- LM uptake in HT was up to 760% greater with PVI versus i.v. (60 min: 80.01 ± 2.87 vs. 10.61 ± 0.96 %ID/g).
- PVI demonstrated significantly higher drug concentrations in HT with minimal washout.
Conclusions:
- PVI significantly increases the concentration of both SM and LM drugs within HT compared to i.v. infusion.
- PVI offers a promising approach for localized treatment of HT using tumor-specific drugs.
- This technique maximizes radiation dose to the tumor while minimizing systemic exposure.
