MPB-1523 MRI Contrast agent for hepatocellular carcinoma
◆ The current causes and diagnosis methods for hepatocellular carcinoma
Generally, like other liver diseases, liver cancer does not show symptoms in the early stage. The condition has usually already become very severe once the symptoms can be felt. The symptoms of liver cancer are related to the size and location of the tumor and this is one of the main reasons that liver cancer has always been the top national killer amongst all cancers. Similar to other cancers, the cause of liver cancer is very complex and is rarely resulted from a single cause. Many academics believe that hepatitis B and hepatitis C are the main original causes of liver cancer. As hepatitis persists along with hepatocyte necrosis, liver cirrhosis and cell carcinoma can start to develop. This will eventually become liver cancer that can be diagnosed clinically.
Liver cancer is malignant cancer with an average age of onset between 50 and 60 years old. If there is no effective treatment, it usually takes only 4-6 months from the onset to death. Clinically, the ability to detect liver cancer early is the key to successful treatment. This is because the early stage of liver cancer tumor usually can be removed by surgery. Based on the statistics, the 10-year survival rate after surgery for tumors smaller than 3 and 2 cm are 40% and 80% respectively.
The initial diagnosis for liver cancer is mainly ultrasound and alpha-fetoprotein (AFP) examination. The AFP count for 85% of patients with large-scale liver cancer will increase. However, for small-scale liver cancer with tumors less than 3cm, only 2/3 of the patients experiences an increase in AFP count. Hence, a normal AFP count does not eliminate the possibility of liver cancer. Abdominal ultrasound can detect whether there are nodules or tumors present in the liver. The sensitivity of abdominal ultrasound to liver cancer is very high and can detect tumors as small as 1cm. However, there are factors which influence the doctor’s interpretation of the ultrasound scan. The factors include excessive gas in the intestine, the uneven liver surface, the fatty liver disease that makes the liver look paler, being blocked by bones or the tumor location is well-hidden.
Both computed tomography (CT) and magnetic resonance imaging (MRI) can provide further information about the nature of the liver tumor and are currently the tools used for diagnosis of liver cancer. There are about 3 million patients with chronic hepatitis B and C in Taiwan. If hepatitis persists and worsens, cirrhosis and liver cancer can develop. Currently, the more accurate tools used to detect liver cancers are CT and MRI. For tumors with sizes between 1 and 2cm, the accuracy of CT is 60% while that of MRI can be up to 80-90%. However, for tumors that are about 1cm, the accuracy of CT is only 10% and that of MRI is reduced to 30-70%. Due to the uneven liver surface resulted from cirrhosis, it is more difficult to use ultrasound and normal MRI to find the liver cancer lesion in cirrhosis patients with hepatitis B and C. As a result, the doctors recommend that these patients should use contrast agent targeting the liver during the annual MRI scan. The sensitivity of this type of contrast agent to tumors can be up to 90%. The contrast agent targeting the liver can reveal early-stage liver cancer that is less than 1cm, and early detection increases the cure rate of the patients.
However, injection of gadolinium (Gd) based contrast agent is usually required to differentiate benign and malignant tumors when diagnosing liver tumors. The traditional linear chelating Gd-based contrast agent uses its characteristic of entering and leaving the blood vessel rapidly to increase imaging intensity of liver tissue. However, it is not specific to the liver tumor. Currently, Primovist (Gd-EOB-DTPA) produced in 2008 is the only contrast agent that is approved by FDA and can diagnose liver cancer effectively.
During the Pharmacovigilance Risk Assessment Committee (PRAC) meeting in July 2017, the European Medicine Agency (EMA) discussed the Gd-based contrast agent used for MRI clinically and suggested to terminate the license for 4 types of linear Gd-based contrast agents. Currently, Primovist® is the only remaining linear Gd contrast agent for liver cancer imaging on the market. Based on the IOP Injection animal testing result, IOP can differentiate hemangioma and tumor effectively and has high accuracy in the range of 0.1-0.5mm. As a result, there are chances that IOP Injection is able to aid in liver tumor diagnosis.
◆ Value Proposition of MPB-1523：
MPB-1523 (IOP Injection) is iron oxide nanoparticles modified by polyethylene glycol and has high magnetic relaxation and high macrophage phagocytosis efficiency. After the macrophages engulf the superparamagnetic iron oxide particles, the signals in the relevant region will decrease. On the other hand, tumor tissue does not have normal macrophages and the signal will remain unchanged. This generates contrast in signals. The aforementioned property can be applied to the create image contrast of organs and tissues rich in reticuloendothelial cells such as liver, spleen and lymph nodes, allowing medical personnel to decide whether the tumor is benign or malignant and whether lymphatic metastasis has occurred. Hence, the product as the following advantages.：
- Accurately differentiate benign hemangioma and malignant tumor.
- No doubts about Gd residues in the body.
◆ The progress of Clinical Trial for MPB-1523：
It has completed Phase I of clinical trials in the Taipei Veterans General Hospital and received approval from TFDA to conduct Phase II of clinical trials in 5 hospitals including National Taiwan University Hospital.
◆ Related clinical trial inquiry
If you need more information，Please go http://www1.cde.org.tw/ct_taiwan/archive1.html Search keyword “巨生”
or https://clinicaltrials.gov/ct2/home ，Other Term Search keyword “Megapro”