Assessment of cell damage produced by 161Tb-/177Lu-somatostatin analog radiopharmaceuticals

The use of 161Tb has been proposed for targeted radionuclide therapy (TRT) because its decay properties are quite similar to those of 177Lu, which is currently the most used radionuclide in TRT. 161Tb emits low-energy photons that are useful for SPECT imaging and relatively low-energy β--particles. However, unlike 177Lu, 161Tb emits a significant number of internal conversion electrons (IE) and Auger electrons (AE) with energies ≤ 40 keV, which could be an advantage to improve the therapeutic efficacy. Moreover, in vitro and in vivo characteristics of 2 somatostatin (SST) analogs labeled with both 161Tb and 177Lu using DOTA as chelating agent demonstrated that both radionuclides produce stable complexes with very similar biodistribution and pharmacokinetics properties. In this research, the biological damage produced to AR42J cells clusters of different sizes by three different SST analog radiopharmaceuticals (RFs) labeled with 161Tb or 177Lu located in different regions within the cells was assessed. For this purpose, the cellular dosimetry and cell surviving fraction assessments using the MIRDcell code were performed. Dosimetry evaluations reveal that most of the beta--particles emitted by 177Lu can penetrate from the membrane to the nucleus. Therefore, 177Lu-RPs localization within the cells does not affect the nucleus absorbed dose (AD) and the generated biological damage. In contrast, 161Tb-RPs localization causes differences in the nucleus AD due to the IE and AE emitted by 161Tb increase the nucleus AD and reduce the cell survival when the radiotracer is localized inside the cell. In conclusion, 161Tb is a better option than 177Lu to label STT ligands due to the induction of greater biological damage for the same number of disintegrations.