Alexander Popov

Radionuclide-based molecular imaging modalities are active and developing areas of functional and molecular diagnosis. Among the radionuclides used for SPECT imaging in oncology, ^99mTc is a leading candidate for radiolabeling. At present, a sufficient number of complexons for ^99mTc have been described; however, the development of effective delivery systems for this isotope to the area of interest is a complex research task. The use of tumor-targeting molecules as carriers for radioactive tracers is an effective strategy that has enabled the development of many novel radiopharmaceuticals for cancer imaging. Background: To date, a number of studies have shown tumorotropicity of tetrapyrrole compounds to tumor tissues, in particular derivatives of natural chlorophyll A. Methods: Purification was performed using solid-phase extraction. Assessment of radiochemical yield and purity was performed via radio-ITLC. The in vitro tumor cell accumulation was assessed using SKOV-3 and A-431 cell lines. Dose-dependent biodistribution was evaluated in Nu/J mice bearing epidermoid carcinoma (A-431) xenografts. Results: In this work, we obtained complexes with ^99mTc based on water-soluble carboxylate chlorin e₆ derivatives in order to evaluate their potential for use as SPECT radiopharmaceuticals. We performed radiolabelling optimization of a series of the novel chlorins and primary preclinical studies, including an assessment of the effect of their lipophilicity and charge on tumor uptake. Conclusions: Modification of the periphery of the chlorin macrocycle with chelating groups allows for complexing a wide range of metals, including ^99mTc, which can be used for targeted delivery of the radionuclide to the area of interest.

The use of radiopharmaceuticals for diagnostics in oncology allows for the detection of the disease at an early stage. Among diagnostic radionuclides, ^99mTc is a promising isotope that has been used to create several drugs for clinical use. One of the most effective ^99mTc chelators is 6-hydrazinylnicotinic acid (HYNIC), which, when combined with various vector molecules, can be used for targeted delivery of radionuclides to tumor tissues. At the same time, it is known that tetrapyrrole macrocycles are capable of selective accumulation in tumors, and thus can be used to target radiopharmaceuticals with ^99mTc. In this work, the conjugate of natural chlorin and HYNIC was obtained, and preliminary preclinical studies were carried out on its radiocomplex with ^99mTc.

Combined therapy is currently a popular method for increasing the efficiency of antitumor treatment. It involves the use of two different tumor treatment methods, namely, chemotherapy and PDT. Combining a cytotoxic agent and a photosensitizer in a single molecule results in a synergistic antitumor effect that overcomes the multiple drug resistance and reduces the therapeutic drug doses. In this work, pyridine-containing natural chlorins were obtained by introducing a pyridine group into 13¹-[ ]-(4-aminobutyl)amide of chlorin [ ] and its bacteriochlorin analogue, [ ]-propyloxime-[ ]-propoxybacteriopurinimide as well as [ ]-aminobacteriopurinimide methyl ester. Moreover, a terpyridine residue was introduced as an external chelating moiety into [ ]-hydroxypurpurinimide and [ ]-aminobacteriopurinimide, and platinum complexes of all the above photosensitizers were obtained. The interactions of the latter with DNA were simulated and the lead compound, the platinum complex of pyridine derivative 13¹-[ ]-(4-aminobutyl)amide chlorin [ ], which may become a potential agent for combined photodynamic and chemotherapy in oncology, was selected. The ability of the compounds obtained to manifest photodynamic and chemocytotoxic effects on tumor cells of various genesis was shown.

When conducting combined therapy of malignant neoplasms, treatment methods with various mechanisms of antitumor effects are used, while an additive or even synergistic effect can be realized. Combination treatment regimens are aimed at increasing the efficiency and, above all, at the complete eradication of the tumor, which can be achieved either by suppressing the survival mechanisms in PDT-resistant tumor cells or by pre-attenuation of tumor cells so that they become more susceptible to subsequent PDT. Photodynamic therapy is an approved medical technology for the treatment of various malignant neoplasms, and several precancerous and non-cancer diseases. To date, numerous data have been published on the combined use of PDT with traditional and innovative methods of treatment. This review considers research in this area in recent years.