The Emission of Internal Conversion Electrons Rather Than Auger Electrons Increased the Nucleus-Absorbed Dose for 161 Tb Compared with 177 Lu with a Higher Dose Response for [ 161 Tb]Tb-DOTA-LM3 Than for [ 161 Tb]Tb-DOTATATE.

Autor:	Spoormans K; Nuclear Medical Applications, Belgian Nuclear Research Center, Mol, Belgium; and kaat.spoormans@sckcen.be.; Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium., Struelens L; Nuclear Medical Applications, Belgian Nuclear Research Center, Mol, Belgium; and., Vermeulen K; Nuclear Medical Applications, Belgian Nuclear Research Center, Mol, Belgium; and., De Saint-Hubert M; Nuclear Medical Applications, Belgian Nuclear Research Center, Mol, Belgium; and., Koole M; Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium., Crabbé M; Nuclear Medical Applications, Belgian Nuclear Research Center, Mol, Belgium; and.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2024 Oct 01; Vol. 65 (10), pp. 1619-1625. Date of Electronic Publication: 2024 Oct 01.
DOI:	10.2967/jnumed.124.267873
Abstrakt:	Preclinical data have shown that ¹⁶¹ Tb-labeled peptides targeting the somatostatin receptor are therapeutically more effective for peptide receptor radionuclide therapy than are their ¹⁷⁷ Lu-labeled counterparts. To further substantiate this enhanced therapeutic effect, we performed cellular dosimetry to quantify the absorbed dose to the cell nucleus and compared dose-response curves to evaluate differences in relative biological effectiveness in vitro. Methods: CA20948 cell survival was assessed after treatment with [ ¹⁶¹ Tb]Tb- and [ ¹⁷⁷ Lu]Lu-DOTATATE (agonist) and with [ ¹⁶¹ Tb]Tb- and [ ¹⁷⁷ Lu]Lu-DOTA-LM3 (antagonist) via a clonogenic assay. Cell binding, internalization, and dissociation assays were performed up to 7 d to acquire time-integrated activity coefficients. Separate S values for each type of particle emission (Auger/internal conversion [IC] electrons and β ^- particles) were computed via Monte Carlo simulations, while considering spheric cells. Once the absorbed dose to the cell nucleus was calculated, survival curves were fitted to the appropriate linear or linear-quadratic model and corresponding relative biological effectiveness was evaluated. Results: Although the radiopeptide uptake was independent of the radionuclide, [ ¹⁶¹ Tb]Tb-DOTATATE and [ ¹⁶¹ Tb]Tb-DOTA-LM3 delivered a 3.6 and 3.8 times higher dose to the nucleus, respectively, than their ¹⁷⁷ Lu-labeled counterparts on saturated receptor binding. This increased nucleus-absorbed dose was mainly due to the additional emission of IC and not Auger electrons by ¹⁶¹ Tb. When activity concentrations were considered, both [ ¹⁶¹ Tb]Tb-DOTATATE and [ ¹⁶¹ Tb]Tb-DOTA-LM3 showed a lower survival fraction than did labeling with ¹⁷⁷ Lu. When the absorbed dose to the nucleus was considered, no significant difference could be observed between the dose-response curves for [ ¹⁶¹ Tb]Tb- and [ ¹⁷⁷ Lu]Lu-DOTATATE. [ ¹⁶¹ Tb]Tb-DOTA-LM3 showed a linear-quadratic dose response, whereas [ ¹⁶¹ Tb]Tb-DOTATATE showed only a linear dose response within the observed dose range, suggesting additional cell membrane damage by Auger electrons. Conclusion: The IC, rather than Auger, electrons emitted by ¹⁶¹ Tb resulted in a higher absorbed dose to the cell nucleus and lower clonogenic survival for [ ¹⁶¹ Tb]Tb-DOTATATE and [ ¹⁶¹ Tb]Tb-DOTA-LM3 than for the ¹⁷⁷ Lu-labeled analogs. In contrast, [ ¹⁶¹ Tb]Tb-DOTATATE showed no higher dose response than [ ¹⁷⁷ Lu]Lu-DOTATATE, whereas for [ ¹⁶¹ Tb]Tb-DOTA-LM3 an additional quadratic response was observed. Because of this quadratic response, potentially caused by cell membrane damage, [ ¹⁶¹ Tb]Tb-DOTA-LM3 is a more effective radiopeptide than [ ¹⁶¹ Tb]Tb-DOTATATE for labeling with ¹⁶¹ Tb. (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze:	MEDLINE
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