Dual-Tracer PET Imaging to Track Liver Cancer Therapy
Abstract
This application proposes to develop a new two-probe imaging strategy to guide effective therapy for liver cancer under Fiscal Year 2021 (FY21) Peer Reviewed Cancer Research Program (PRCRP) Topic Area of Liver Cancer. Primary liver cancers such as the hepatocellular carcinoma (HCC), the third leading cause of cancer-related death worldwide, is difficult to treat, and it impacts the lives of the military, Veterans, and their families as well as the civilian. There are enzymes in our body, many of them reside in the liver. They have their normal functions to support metabolism and physiology, but also play an important role, sometimes unique role, to convert harmless drugs (pro-drugs) into active cancer fighting therapeutics. Many pro-drugs were developed mimicking the building blocks of our genetic materials (DNA) to interfere or block the synthesis of genetic materials needed for tumor progression. This application deals with two of these enzymes (key players), each responsible for activating a class of the pro-drugs. Our previous research discovered that after an extended treatment using a specific (targeting one of the players) class of drugs, there will be a shift of the player’s activity from initially high to low while the other player’s activity goes from low to high in the process. Therefore, continuing treatment with the initial drug wouldn’t stop tumor growth, because it shifts to the other player once the current player is pinned down by the initial drug, a term called drug-resistance. As the resistance is caused by the activity shifting from one player to the other, we need to switch to a different class of drugs matching (targeting) the player with high activity, accordingly. However, this shift is not visible, and painful biopsies are usually needed to obtain tissue samples for molecular and pathological evaluation for determination. To avoid such repeated liver biopsy to cancer patients, we proposed a new two-probe imaging approach, one for each of the players. Such imaging approach will be developed so that in the future, patients just need to go to the Nuclear Medicine suite of the Radiology Department in a hospital for two consecutive scans, each with a radiolabeled probe to measure the activity of a specific player. In this way, we can get a quantitative readout of the internal activities of the two key players without sticking the needles into the patients’ liver repeatedly during the course of treatment. Liver cancer impacts our Service Members, Veterans, and their beneficiaries more than the general public due to higher risk factor associated such as the viral hepatitis infection in the far east (where there is a very large contingent of our armed force stationing long-term). Chronic viral hepatitis infection often leads to primary liver cancer. As mentioned above, liver cancer once formed is difficult to treat. It is important to identify the key player to maximize a targeting (matching) treatment regimen. The proposed two-probe imaging approach will initially help determine the dominant player for activating its matching pro-drug. During the course of the treatment, the two-probe scans will follow each cycle of the treatment to detect any resistance (metabolic shift) discussed above, and will switch treatment according to the shifting dominance between the players to overcome drug-resistance and minimize liver cancer relapse. The FY21 PRCRP Overarching Challenge to be studied is to develop strategies and biomarkers to predict treatment resistance to mitigate risk in target populations. Resistance/relapse will surely develop during the course of cancer therapy as discussed above. We propose to develop a new two-probe imaging approach to measure the shifting activities of two key players involved in the activation of the specific cancer pro-drugs of our interest in real-time in liver cancer non-invasively as crucial biomarkers of resistance, to thereby rationally guide treatment
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210784
Entities
People
- Zhenghong Lee
Organizations
- Case Western Reserve University
- United States Army