Terbium-161 Delivers More Radiation to Cancer Cell Nuclei Than Lutetium-177 in Peptide Radionuclide Therapy

161Tb-DOTATATE and 161Tb-DOTA-LM3 delivered 3.6× and 3.8× higher nuclear absorbed doses than 177Lu-labeled counterparts. The enhanced dose was primarily from internal conversion electrons, not Auger electrons. 161Tb-DOTA-LM3 showed a superior linear-quadratic dose response (suggesting additional membrane damage) compared to the linear-only response of 161Tb-DOTATATE.

In vitro study using CA20948 neuroendocrine tumor cells. Clonogenic survival assays compared cell killing by 161Tb vs 177Lu with both DOTATATE and DOTA-LM3 peptides. Cell binding, internalization, and dissociation measured over 7 days. Monte Carlo simulations computed separate S values for each particle emission type. Survival curves fitted to linear or linear-quadratic models.

177Lu-DOTATATE is already an approved, effective treatment for neuroendocrine tumors. If 161Tb can deliver 3-4 times more radiation to tumor cell nuclei using the same targeting peptides, it could significantly improve treatment outcomes for patients with neuroendocrine cancers — and the antagonist peptide DOTA-LM3 may offer even greater benefit.

Peptide receptor radionuclide therapy has transformed neuroendocrine cancer treatment. The shift from 177Lu to 161Tb could represent the next major advance, delivering more targeted radiation damage while using the same proven peptide-targeting platform. Combined with antagonist peptides that bind more receptors without internalizing, this could dramatically improve patient outcomes.

In vitro study using a single cell line — tumor heterogeneity and microenvironment effects are not captured. 161Tb is not yet widely available for clinical use. Monte Carlo simulations assumed spherical cells, which may oversimplify actual cell geometry. The study didn't account for bystander effects or DNA repair capacity differences between cell types.