Specifics of Clinical Trials of Radiopharmaceuticals in Russia

It is difficult to imagine modern medicine without radiological methods of diagnosis and treatment of patients. Almost every district clinic has equipment for radiological diagnostics. In many cities it is possible to have a CT scan when a quick and accurate diagnosis and localization of tissue lesions are required, but also for routine examinations, for example, before a brace system is installed.

Almost every district clinic has equipment for radiological diagnostics. In many cities, computed tomography can be performed when a quick and accurate diagnosis and localization of tissue lesions is required and for routine examinations, for example, before a brace system is placed.

Radiation therapy, also called radio- or radiation therapy, is no less developed. Radiotherapy is a treatment with ionizing radiation and is most commonly used in oncology to treat malignant tumors. The purpose of radiotherapy is to destroy the cells that make up a malignant tumor. This is achieved through the ability of ionizing radiation to damage the DNA of cancer cells, thereby stopping their uncontrolled reproduction.

There are three ways to treat a tumor in radiation therapy:

1. Remote is the most commonly used method. With the remote method of action, healthy tissues may be located between the focus of action and its “target”, which entails many negative side effects.
2. Contact is the radiation source is located in the immediate vicinity of the tumor: in the focus or in the space next to the tumor. This allows for fewer radiation sessions compared to the distant method, but this method of exposure is technically more complex.
3. Radionuclide therapy – a radioactive nuclide as an independent agent or as part of a radiopharmaceutical  in the form of a solution is injected into the patient’s body orally, intravenously, or directly into the tumor.

In this article, we want to talk in detail about radionuclide therapy, its advantages, general criteria for the effectiveness of radiopharmaceuticals, and the peculiarities of clinical trials of radiopharmaceuticals.

Like chemotherapy, radionuclide therapy is a systemic treatment, meaning that the drug reaches the cells throughout the body with the bloodstream. However, unlike chemotherapy, these radioactive substances specifically target the malignant cells. In this way, the number of potential side effects is reduced. Only RFAs that are able to form a strong bond with the tumor, so-called carriers that have a high affinity for the tumor, are suitable for treatment. These agents can deliver targeted doses of radiation directly to tumors and their metastases, with minimal effect on healthy tissues and organs.

In general, the ideal radiopharmaceutical has the following properties:

• reaches all malignant cells in all places where they are localized;
• acts exclusively on the cells that make up a malignant tumor and metastases;
• does not harm healthy tissues and organs, while delivering maximum doses of ionizing radiation to the malignant tumor;
• eliminates cells of the malignant tumor with great effectiveness.

To register a radiopharmaceutical, of course, preclinical and clinical studies are required. There are a number of peculiarities.

On the one hand, preclinical and clinical studies of radiopharmaceuticals are similar to studies of drugs used for cancer chemotherapy:

• Due to the high toxicity of both radiopharmaceuticals and chemotherapy, phase I studies are not conducted with healthy volunteers, but with patients suffering from the corresponding disease.
• Studies of both radiopharmaceutical  s and other chemotherapy drugs are generally not placebo-controlled, since the use of placebos is unethical with respect to patients.

However, because radiopharmaceutical, unlike any other drugs, is radioactive, there are many peculiarities of both treating patients with radiopharmaceutical  s and conducting clinical trials of radiopharmaceuticals:

• First of all, being radioactive, radiopharmaceuticals are so-called open sources, i.e., these drugs can have an impact on the environment, the patient, medical personnel, and personnel involved in the production of radiopharmaceutical s. This circumstance leads to the necessity of strict compliance with the requirements of the Federal Law “On Radiation Safety of the Population”.
• Secondly, due to the detrimental effect of radiation on biological systems, of medical value are radionuclides with a relatively short half-life to ensure a short-term effect of radiation on the body. Thus, the production of radiopharmaceuticals must be:

1. 1. Very rapid and be carried out in relative proximity to the medical facility where the drug will be used on patients. For example, the production of the radiopharmaceutical can be organized on the premises of a medical radiological trial site.
   2. If the physical half-life is ultra-short, and if the radiopharmaceutical can be produced by simply combining the radionuclide with a non-radioactive carrier, the radiopharmaceutical can be produced shortly before administration to the patient by dividing production into several stages. In this case, production can be partially organized at a nuclear power plant (NPP), while the actual “combination” is performed by specialists in the laboratory of the medical institution where the radiopharmaceutical is to be administered to the patient.

Thus, clinical trials of radiopharmaceuticals are among the most difficult not only because of the nosology under study, but also because of a number of peculiarities of the radiopharmaceutical, which we have discussed in this article. A successful clinical trial of an radiopharmaceutical requires the coordinated work of medical personnel, radiopharmaceutical developers, and the contract research organization (CRO).