Unmet NeedHepatocellular carcinoma (HCC) is the fifth most common cancer type worldwide and a leading cause of cancer related deaths. HCC is clinically silent in its early stages, leading to diagnosis at more advanced stages when only non-surgical, palliative treatment is available. One treatment option for advanced HCC is intra-arterial therapy and embolization, as the hepatic artery is the tumor’s major blood supply. Transarterial radioembolization (TARE), which combines embolization and radiation therapy, has demonstrated promise for treating HCC. However, current TARE strategies rely on emulsified β-emitting particles (βRPT) that are less potent than other radionuclides and have a long range that can expose normal tissue to high doses of radiation and thus toxicity. Post-embolization syndrome (PES) is also a very common side effect of TARE. Consequently, there is a need to develop novel TARE strategies for liver cancer using emulsions that result in lower rates of PES following treatment and radionuclides that are highly damaging over a short range to only cancerous cells.
Technology OverviewJohns Hopkins researchers have developed a novel TARE strategy for HCC and other liver metastases that utilizes αRPT agents, which are potent, have a short range, and are generally impervious to cellular resistance mechanisms. Prior to delivery to the hepatic artery, these agents are emulsified in the FDA-approved Lipiodol, which has been shown to minimize PES when incorporated into embolization formulas. The researchers generated a preliminary αRPT-Lipidol emulsion labeled with
225Ac that was injected into the hepatic artery of rabbits with a VX2 liver tumor. This novel αRPT-Lipidol emulsion accumulated in the tumor but cleared out of normal liver tissue, resulting in a 13:1 tumor to liver ratio. These results indicate that αRPT-Lipidol emulsions could be a novel delivery mechanism for radionuclides in targeted therapy regimens for primary and metastatic liver cancer.
Stage of DevelopmentThe inventors have identified a novel TARE strategy for improved treatment of advanced-staged liver cancer. Further studies are required to identify optimal and highly potent αRPT agents capable of accumulating at the tumor site with minimal off-target effects that also demonstrate therapeutic efficacy
in vivo. Optimization of radiolabeling and emulsification will be performed along with the development of an αRPT imaging strategy for guided treatment and prognostication.
