Post-effects of radioactive decay in ligands on biologically active transport platforms

Abstract

The electron capture consequences in the 57Co DOTA complex compound and processes of radiation-induced defect formation in DOTA under the effect of recoil nuclei produced after the α-decay of 241Am were studied using high performance liquid radiochromatography and emission Mössbauer spectroscopy. The experiments conducted have shown that the production of targeted RPHs on the base of alpha-emitters and when applying the conventional approach (biologically active molecular construct with any chelate carrying a radioactive tracer) is just a scientific mystification, since the recoiling alpha-emitting nucleus causes a destroying effect on the neighboring substrate molecules and entirely excludes the targeted transport of the preparation. This is a bold conclusion indeed. However, it is confirmed in part by the works of other authors and by the fact that the encapsulation of α-particle emitters in inorganic (rather than organic) nanocontainers significantly decreases the negative effect of recoil nuclei on the carrier molecule and allows radiation treatment to be done of cancerous tissues, which is similar to hadron therapy. It is the recoiling nuclei (and not at all the emitted alpha-particles) that possess a huge destroying ability and exert a therapeutic effect when conventional approach (biologically active molecular construct with any chelate carrying a alpha-emitters) are used. The amount of radiation-induced damage in a matrix, caused by a recoil nucleus with a typical energy of approximately 100 keV is by a factor of several hundreds higher than the amount caused by the 5–7 MeV α-particles. If a labelled molecular construction has reached the tumor cell, there is no doubt in the “prioritative” action of recoil nuclei as compared to that of α-particles. However, the picture changes dramatically if the recoil impact “is blocked” at the location where an α-particle is emitted (e.g., in inorganic nanocontainers). A success in the development and production of pharmaceutical forms based on alpha-emitters is possible only when the pernicious influence of recoil nuclei is “blocked” owing to a high radiation stability of labelled compounds or owing to other “means of transportation” of the radionuclides to lesions. A reasonable alternative to alpha-emitters might be Auger- and internal conversion electron emitters that possess (as it is shown by the present studies and, which is of more importance, by the worldwide radionuclide practice) by incomparably higher radiation stability of labelled compounds.