Tomsk researchers have developed a new radiopharmaceutical for the diagnosis of an aggressive type of breast cancer, Tomsk Polytechnic University reports. Phase I clinical trial took place during the last year at the Research Institute of Oncology of the Tomsk National Research Medical Center of the Russian Academy of Sciences. 29 patients took part in the phase; the product proved to be successful.
The drug was developed with a technology that is fundamentally new for Russia: the use of a frame protein.
“The peculiarity of the obtained radiopharmaceutical is its structure, which includes a skeleton protein and Technetium-99, a radioactive isotope. The protein is responsible for a very accurate search for a tumor cell and acts based on antigen-antibody principle, whereas the isotope is in charge of visualization, as the location of the isotope, and, therefore, of the tumor cell, can be seen with a gamma camera (a device available in all cancer centers and specialized early treatment centers). Diagnostic drugs with such a structure are considered extremely promising due to their accuracy and lack of toxicity. However, they have not yet been introduced into mainstream use anywhere in the world,” the university press service said in its statement.
The developed drug uses the ADAPT6 framework protein, specific to the Her2/neu cancer marker, which is a receptor on the surface of a tumor cell. The more such receptors there are on a cell, the more aggressive the disease is. 15-20% of patients with breast cancer have an increased expression of this receptor, with up to 2 million Her2/neu receptors on one cell.
“The treatment of this type of breast cancer involves the use of expensive targeted drugs, which should be prescribed on the basis of a most accurate diagnosis in order not to miss tumor cells during treatment, but, at the same time, to minimize the impact of drugs on healthy tissues,” said Olga Bragina, one of the authors of the article, a researcher at Oncoteranostica center at Tomsk Polytechnic University.
At the first stage of the clinical trials, the patients were divided into three groups. Each group was administered one of the three dosages: 250, 500, or 1000 mg. Experts note that even the maximum dosage of the drug used in the study is by an order of magnitude lower than in standard diagnostic drugs used to diagnose other types of cancer. Each patient was administered the product once.
Two, four, six, and twenty-four hours after the administration of the drug the patients had a scan in a gamma camera. This was necessary to assess the rate of distribution of the drug and the rate of its accumulation.
“The trials showed a significant difference in the accumulation of the drug in tumors with Her2/neu overexpression compared to tumors without this receptor, and a high tumor-to-liver ratio. This means that the use of the drug makes it possible to visualize metastases not only in the mammary gland, but also in the liver, if there are any,” Olga Bragina said. “In one case, the Her2/neu status was changed: it was found that the patient had negative expression, and that led to a change in the treatment strategy.
In another case, the patient was found to have additional metastatic foci in the thoracic vertebrae and in the rib, which could not be visualized before by standard diagnostic methods.”
According to experts, the product will have to go through several more stages of clinical trials.
