Liver cancer is one of the leading causes of cancer-related deaths globally, particularly for patients with chronic hepatitis and cirrhosis. Accurate assessment of liver function prior to treatment is crucial to prevent liver failure due to insufficient residual liver function after therapy. Traditional methods for liver function evaluation, such as liver function blood tests, indocyanine green retention tests (ICGR15), or CT/MRI scans, often lack sufficient sensitivity and specificity and can be affected by various factors, making it challenging to accurately reflect liver function. Thus, there is an urgent need for a tool that can accurately assess liver function.

To address this issue, NARI’s Isotope Application Division has developed "Dolacga" for functional liver imaging. Its core component is a hexa-lactosyl-peptide derivative, which features galactose moieties that are specifically recognized by hepatic asialoglycoprotein receptors (ASGPRs). This specificity allows for precise targeting of the liver. When Dolacga is reconstituted with the radioactive isotope gallium-68 and used with positron emission tomography/computed tomography (PET/CT), it provides detailed imaging of ASGPR distribution in the liver.

Figures 1 and 2 illustrate the structure of Dolacga and the asialoglycoprotein receptor, respectively.

The ASGPR is a specific receptor located on the liver cell membrane, primarily responsible for clearing aged glycoproteins from the blood. Its expression is highly correlated with liver function, and a reduction in ASGPR levels is indicative of liver damage. By leveraging this characteristic, PET/CT imaging with Ga-68-Dolacga allows for accurate assessment of liver function and the degree of liver impairment.

Dolacga’s innovative technology has been awarded over 20 patents and numerous domestic and international accolades, underscoring its potential in the field of liver function assessment. Its technical advantages include high specificity, low background absorption, and high sensitivity. Additionally, Dolacga features an "immediate-use" gallium-68 labeling process that requires only 15 minutes, eliminating the need for further purification. In 2024, Dolacga completed Phase II clinical trials for preoperative liver function assessment in hepatocellular cancer (HCC) patients. Preliminary results indicate that Dolacga can significantly differentiate between normal liver tissue and cancerous regions, providing precise quantitative information on liver function to support surgical planning.

Beyond preoperative liver function assessment for liver cancer, Dolacga also holds potential value for patients undergoing proton therapy or chemotherapy for cancer. Both treatments require precise pre-treatment liver function evaluation to prevent excessive liver damage. Dolacga can aid physicians in making more accurate decisions for these treatment modalities, thereby ensuring the safety and efficacy of the therapeutic process.

NARI plans to expand the clinical applications of Dolacga. Currently NARI is collaborating with hospitals to conduct clinical trials that assess residual liver function in liver cancer patients before and after proton therapy. Additionally, NARI is planning for clinical studies to evaluate liver function in cancer patients prior to chemotherapy. These trials will help determine Dolacga's efficacy in various treatment contexts and refine its application strategies.

Furthermore, NARI aims to establish a stable drug supply platform and continue promoting this technology in collaboration with major hospitals. The goal is to provide a more accurate and convenient liver function assessment tool to the global medical community. Future objectives include further optimizing the imaging agent's performance, expanding into international markets, and integrating AI for automated image recognition and analysis, thereby enhancing the clinical value of Dolacga.