Effectiveness of therapeutic radionuclides in targeted treatment

In the last decade, preclinical research in the field of targeted radionuclide therapy began to focus on Auger emitters and emitters undergoing one or more cascaded alpha transformations with the simultaneous emission of both beta and gamma radiation - the so-called 'in vivo' generators. ---- In common clinical practice, ¹³¹I (T_1/2 8.05 days) and ¹⁷⁷Lu (T_1/2 6.65 days) have been used in targeted therapeutic applications for many years. From February 2021, in the Czech Republic, it is available for the treatment of inoperable or metastasizing, well-differentiated (G1 and G2) gastroenteropancreatic neuroendocrine tumors (GEP-NET), which progress on treatment with somatostatin analogues and in which the excessive presence of somatostatin receptors on the surface of the tumor is confirmed by scintigraphy. --- The clinical efficacy of ¹⁷⁷Lu against prostate cancer has also been studied and confirmed. In connection with PSMA and GEP-NETs, the possibilities of using alpha emitters, e.g. ²²⁵Ac and ²¹³Bi, were investigated. Actinium-225 (T_1/2 10 days, α 5.8 MeV) and its daughter radionuclide ²¹³Bi (T_1/2 45 min, a 5.8 MeV (2.1%), β^- 1.4 MeV (98%) ) are studied in several clinical studies and preclinical research. ---- Compared to beta emitters, which are used in therapy for a significantly longer period of time, the mass of emitted a particles is about 7000 times greater than β-particles. At the same time, the energy of a-particles is 10-30 times greater than β-particles: a typically 4-8 MeV and β- approximately 0.2 - 2.25 MeV. The linear energy transfer LET of a-particles is about 100 times greater than that of β-particles. For alpha particles with energies of 4-8 MeV, the LET in the tissue is about 100 keV/micrometer, towards the end of the path in the Bragg maximum it can locally increase to 300 keV/μm. For β-particles with typical energies of hundreds of keV, the LET is only about 0.2 keV/micrometer. However, the effective range of a-particles in the tissue is considerably shorter than that of μ-particles. For a, the range is about 2 - 5 cell diameters, for β - hundreds of cell diameters. Auger emitters are touted as potential competition to beta emitters. Research attention is mainly devoted to the study of ¹⁶¹Tb, which is currently produced at the LVR-15 reactor at the CVR UJV. Assessment of the biological effectiveness of the above-mentioned radionuclides, determination of MTD, blood count and kidney function are, in connection with dosimetry, key parameters for determining the effectiveness and safety of therapy. The aim of the lecture is to show the available preclinical and clinical data from the application of radiopharmaceuticals with the mentioned radionuclides, to try to compare their biological effectiveness and to present possible trends for the future. (authors)