Ural Federal University: New Radiopharmaceuticals Can Diagnose and Treat Tumors More Effectively

Ural scientists determined the characteristics of patient dose loads for promising radiopharmaceuticals labeled with zirconium-89 and lutetium-177 radionuclides. In the practice of radionuclide diagnostics and therapy these radionuclides were most actively introduced in the last decade by efforts of foreign scientists, but detailed data on dose loads on the tumor and other organs and tissues are sketchy or absent at all.

UrFU specialists calculated optimal injectable activities for diagnosis and therapy of bone metastases and solid tumors of various organs and tissues, in particular for lymphoma and prostate cancer. Physicists have shown that the new medications can be highly effective analogues to existing radiopharmaceuticals due to the optimal half-life (3.27 and 6.73 days, respectively) and the low dose of radiation to healthy organs and tissues. Some recent results were published in the journal Applied Radiation and Isotopes.

“Today there is a wide range of radiopharmaceuticals used for radionuclide diagnosis and/or therapy. However, the world is constantly searching for more effective medications with the necessary radiation-physical properties: the half-life of the radionuclide, the degree of impact on tumor cells and healthy tissues. The main requirement is to reduce the degree of their radiotoxicity – because some modern medications give a rather high dose load not only on the tumor, but also on healthy tissues, which leads to pronounced side effects,” explains Mikhail Zhukovskiy, Chief Researcher at the Institute of Industrial Ecology, Ural Branch of Russian Academy of Sciences, Professor at the Department of Experimental Physics, UrFU.

The study was conducted in several steps. First, using a biokinetic model based on laboratory data on mice and a limited amount of clinical data on patients, physicists evaluated dose loads with zirconium-89 and lutetium-177-based radiopharmaceuticals. They determined how much the medications directly irradiate the tumor and affect healthy organs and tissues nearby. Second, they analyzed the effectiveness of radionuclides in combination with various vector “delivery agents” (monoclonal antibodies (MAb) rituximab, tetulomab, cetuximab and huA33 and their fragments). As a result, the most effective combination of these isotopes with medications for targeted radionuclide delivery to the tumor was identified. Lutetium-177-labeled cetuximab has the best ratio of absorbed doses to tumors and organs. Two other medications labeled with lutetium-177 showed advantages over conventional medications for palliative therapy of pain syndrome in bone metastases: methylenediphosphonate and ethylenediaminetetramethylene phosphonic acid.

“Currently, the development of both radionuclide diagnostics and therapy is very intensive. New carriers (MAb, peptides, proteins, etc.) and radionuclides are constantly being proposed. At the same time, the issue of dosimetric assessment of the effect of the medication on healthy organs and tissues and the assessment of long-term consequences of such radiation exposure is not always well addressed. Although it is extremely important to ensure comfortable and safe treatment of the patient. In addition, the lack of substantiated assessments of dose coefficients on organs and tissues when using new radiopharmaceuticals is a serious obstacle to their certification and introduction into the practice of use in clinics,” says Mohamed Hesham Mahmoud Hamed, Engineer at the Ural Federal University Department of Experimental Physics.

Preclinical and clinical trials of the new medications could be the next stage of the work. The results of the dose-response assessments, according to the scientists, can be useful to other researchers when working with other medications.

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