Assessment of cell damage produced by somatostatin analog radiopharmaceuticals labelled with lutetium‑177 or terbium‑161

Aim: 177Lu-labeled radiopharmaceuticals (RPs), are currently the most widely used for targeted radionuclide therapy (TRT), as they have demonstrated favorable safety and good response rates to treatment [1]. However, worldwide 177Lu availability is limited [2]. To overcome this problem, the use of 161Tb for TRT has been proposed because its decay characteristics are quite similar to those of 177Lu [3]. 161Tb emits low-energy photons (48.9 keV (17%) and 74.6 keV (10%)), useful for SPECT imaging, and relatively low-energy β-particles (Eavg = 154 keV). Unlike 177Lu, 161Tb emits a significant number of internal conversion (IE) and Auger electrons (AE) with energies ≤ 40 keV, which could be advantageous for improving therapeutic efficacy [4]. The aim of this study was to evaluate and compare the biological damage produced by 161Tb-labeled somatostatin (SST) and 177Lu-labeled SST analog RPs localized in different regions within pancreatic tumor AR42J cells [5]. Materials and methods: The biological damage caused to AR42J cell clusters of different sizes by three different SST analog RPs, labeled with 161Tb or 177Lu and located in different regions within the cells, was obtained with the MIRDcell code [6] by evaluating the absorbed dose (AD) to the cell nuclei and the cell survival fraction (Sf). MIRDcell calculated the Sf for each treatment using the linear quadratic model equation and taking into account the AD generated by the radiation emitted within the same cell (self ) and the radiation emitted by neighboring cells (cross). The α and β values of AR42J cells were determined experimentally. Results: Dosimetric evaluations show that most of the β-particles emitted by 177Lu penetrates the membrane and reaches the nucleus to deliver a specific fraction of their energy. Therefore, 177Lu-labeled RPs localization inside the cells only slightly affects the AD and the biological damage generated. In contrast, 161Tb-labeled RPs localization causes differences in AD due to the IE and AE emitted by 161Tb. However, as the cluster size increases, the difference in AD due to RPs localization is minimal and the Sf depends mainly on the number of labelled cells. Conclusion: For both 177Lu-labeled RPs and 161Tb-labeled RPs the main factors affecting the biological outcome are the dimensions of the cell cluster and the fraction of labelled cells inside the cluster. For a fixed cluster size and % of labelled cells, the localization of the RP inside the different cell compartments has a minimal influence on the AD to the cell nuclei and cell survival.