Accurate to the millimeter
A new method for the diagnosis of cancer and metastases has been developed
Scientists of the Krasnoyarsk Scientific Center SB RAS have developed a new drug based on aptamers for the detection of cancerous tumors and their metastases. The component allows you to detect clusters of cancer cells in the body with a size of two millimeters and does not give false positive results. This will significantly improve the accuracy of cancer diagnosis and monitoring of their recurrence. The results of the study are published in the journal Molecular Therapy — Nucleic Acids (Ozerskaya et al., 11C-radiolabeled aptamer for imaging of tumors and metastases using positron emission tomography- computed tomography Author links open overlay panel).
The spread of cancer cells through the blood and lymph begins in the early stages of the disease. Sometimes this happens even before the primary tumor becomes large enough to be visualized using positron emission tomography, magnetic resonance imaging or computed tomography. Traditional methods for determining the localization of metastases in the body are not sensitive enough and specific enough to distinguish transformed tissues of small size. It is necessary to create a drug capable of selectively marking tumor foci even of critically small sizes, at the same time, so that visualization could be carried out on existing standard scanners.
A team of scientists from Siberia, which included researchers from the Krasnoyarsk Scientific Center SB RAS, with the participation of colleagues from the University of Ottawa (Canada), has developed a new radiopharmaceutical based on aptamers for the detection and visualization of cancerous tumors and metastases using positron emission and computed tomography. This will significantly increase the accuracy of diagnosis and monitoring of cancer development.
In the new method, scientists used anti-cancer DNA aptamers labeled with radioactive carbon to detect the localization of tumors and metastases. Aptamers are short oligonucleotide molecules synthesized in the laboratory that can bind to certain cells or other molecules. It is a cheaper and completely non-toxic alternative to antibodies as a means of targeting, diagnosis and delivery of medicines. The carbon isotope used as a label is one of the most rapidly decaying and safe radionuclides and does not affect the chemical structure and properties of the biomolecule.
The resulting system was tested on mice with Ehrlich's ascitic carcinoma and its metastases. An aptamer with a radioactive label made it possible to identify primary and secondary tumors smaller than two millimeters, whereas radioactive glucose, which is now used as a standard, determines only seven-millimeter foci. Experts also note that such a combination of components presents highly specific and high-contrast images of cancer cells, does not give false positive results and can be used for targeted drug delivery.
"The identification of primary tumors and metastasis sites is an important step in cancer diagnosis and monitoring of subsequent treatment. The synthesis of new radiopharmaceuticals for the treatment of cancer metastases is of great importance, since existing radionuclides for cancer imaging do not demonstrate sufficient selectivity, accumulating in tumors and tissues with high metabolic activity. The advantages of aptamers as radioactively labeled probes for cancer imaging are specificity to targets and their rapid elimination from the body without tissue damage. High specificity and affinity to the target receptor or cell, as well as the small size of aptamers provide good penetration into the tumor and contrast image. For visualization, we labeled the aptamer with a radioactive carbon isotope with a short half-life. Standard radiopharmaceuticals have a resolution limit of eight square millimeters. The carbon isotope aptamer had a much higher resolution, less than two square millimeters. We were able to distinguish small metastatic lesions throughout the body: in the thyroid gland, stomach, liver, kidneys, intestines, muscles, lungs, heart, pancreas and even in the bone marrow of the ribs. The created drug was completely eliminated from the body within an hour. The study of acute toxicity showed that the aptamer-based drug is not toxic. Therefore, it opens up new opportunities for cancer diagnosis," she shared the results of her work. Anna Kichkailo, Doctor of Biological Sciences, Head of the Laboratory of Digital Controlled Drugs and Theranostics of the FITC KNC SB RAS, Head of the Laboratory of Biomolecular and Medical Technologies of the Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky.
It should be noted that the graphic image of the results of the study by Siberian scientists became the cover of the December issue of the journal Molecular Therapy - Nucleic Acids. Usually, the brightest and most interesting result is chosen as an illustration for the cover of a scientific journal.
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