# Alpha-Particle Emitter Radiopharmaceutical Therapy for Liver Cancer

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $574,001

## Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the fifth most frequently
diagnosed cancer worldwide, as well as the second most frequent cause of cancer death. Furthermore, the liver
is also the most common site for metastatic cancer. Most patients with advanced disease are offered only non-
surgical palliative treatment options. Hepatic tumors derived their blood supply from the hepatic artery whereas
normal liver tissue’s blood supply is mainly sourced from the portal vein. Intra-arterial therapies, such as
chemoembolization and radioembolization, exploit the hepatic tumors’ blood supply via the hepatic artery to
selectively deliver contrast and therapies. Lipiodol is an FDA approved radio-opaque contrast agent used in liver
tumor imaging during intra-arterial therapies. Lipiodol accumulates and remains in the tumor while clearing out
of normal liver tissue when injected via the hepatic artery, providing a vehicle to deliver therapeutic agents, such
as, chemotherapeutics and -emitting radionuclides (188Re and 131I) to liver tumors, but these treatments have
limitations, urging the need for development of new therapies. Alpha-emitting radiopharmaceutical therapy
(RPT) is highly potent, causing largely irreparable DNA damage to targeted cells. Due to the short range of
alpha particles, RPT minimizes damage to nearby healthy cells. The high-energy transfer of alpha particles
makes RPT impervious to most resistance mechanisms including pathway redundancy and oxygenation status,
a desirable feature for treatment of liver tumors. Lipiodol has detailed information on its pharmacology,
formulation and toxicity, due to its FDA-approved status, and its repurposing for RPT can build upon information
from previous studies for FDA approval to help rapidly translate a novel RPT agent-Lipiodol emulsion to the
clinic. The proposed work is focused on evaluating targeted RPT emulsions for unresectable primary liver
cancer as compared to standard of care treatment (Aim 1). A selected RPT emulsion will be tested in a technical
rabbit VX2 liver cancer model, allowing us to evaluate these agents’ distribution via the hepatic artery (Aim 2).
Finally, the proposed work is focused on the development of a companion imaging agent or the expansion of
imaging protocols to allow for a single theranostic agent (Aims 1-3). The successful completion of the proposed
research is that an RPT agent-Lipiodol emulsion, based on current FDA approved Lipiodol emulsions, can be
repurposed for quick development and evaluation as a therapeutic or theranostic agent for primary and
metastatic liver cancer.

## Key facts

- **NIH application ID:** 10744755
- **Project number:** 5R01CA239041-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Jessie Nedrow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $574,001
- **Award type:** 5
- **Project period:** 2019-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10744755

## Citation

> US National Institutes of Health, RePORTER application 10744755, Alpha-Particle Emitter Radiopharmaceutical Therapy for Liver Cancer (5R01CA239041-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10744755. Licensed CC0.

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