Membrane and Nuclear Absorbed Doses from 177Lu and 161Tb in Tumor Clusters: Effect of Cellular Heterogeneity and Potential Benefit of Dual Targeting—A Monte Carlo Study
J Nucl Med. 2023-06-15; : jnumed.123.265509
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Larouze A(1), Alcocer-Ávila M(1), Morgat C(2), Champion C(3), Hindié E(4)(5).
(1)Université de Bordeaux-CNRS-CEA, Centre Lasers Intenses et Applications, UMR
5107, Talence, France.
(2)Service de Médecine Nucléaire, CHU de Bordeaux, Université de Bordeaux, UMR
CNRS 5287, INCIA, Talence, France; and.
(3)Université de Bordeaux-CNRS-CEA, Centre Lasers Intenses et Applications, UMR
5107, Talence, France; .
(4)Service de Médecine Nucléaire, CHU de Bordeaux, Université de Bordeaux, UMR
CNRS 5287, INCIA, Talence, France; and
(5)Institut Universitaire de France, Paris, France.
Early use of targeted radionuclide therapy to eradicate tumor cell clusters and
micrometastases might offer cure. However, there is a need to select appropriate
radionuclides and assess the potential impact of heterogeneous targeting.
Methods: The Monte Carlo code CELLDOSE was used to assess membrane and nuclear
absorbed doses from 177Lu and 161Tb (β–emitter with additional conversion and
Auger electrons) in a cluster of 19 cells (14-μm diameter, 10-μm nucleus). The
radionuclide distributions considered were cell surface, intracytoplasmic, or
intranuclear, with 1,436 MeV released per labeled cell. To model heterogeneous
targeting, 4 of the 19 cells were unlabeled, their position being stochastically
determined. We simulated situations of single targeting, as well as dual
targeting, with the 2 radiopharmaceuticals aiming at different targets. Results:
161Tb delivered 2- to 6-fold higher absorbed doses to cell membranes and 2- to
3-fold higher nuclear doses than 177Lu. When all 19 cells were targeted,
membrane and nuclear absorbed doses were dependent mainly on radionuclide
location. With cell surface location, membrane absorbed doses were substantially
higher than nuclear absorbed doses, both with 177Lu (38-41 vs. 4.7-7.2 Gy) and
with 161Tb (237-244 vs. 9.8-15.1 Gy). However, when 4 cells were not targeted by
the cell surface radiopharmaceutical, the membranes of these cells received on
average only 9.6% of the 177Lu absorbed dose and 2.9% of the 161Tb dose,
compared with a cluster with uniform cell targeting, whereas the impact on
nuclear absorbed doses was moderate. With an intranuclear radionuclide location,
the nuclei of unlabeled cells received only 17% of the 177Lu absorbed dose and
10.8% of the 161Tb dose, compared with situations with uniform targeting. With
an intracytoplasmic location, nuclear and membrane absorbed doses to unlabeled
cells were one half to one quarter those obtained with uniform targeting, both
for 177Lu and for 161Tb. Dual targeting was beneficial in minimizing absorbed
dose heterogeneities. Conclusion: To eradicate tumor cell clusters, 161Tb may be
a better candidate than 177Lu. Heterogeneous cell targeting can lead to
substantial heterogeneities in absorbed doses. Dual targeting was helpful in
reducing dose heterogeneity and should be explored in preclinical and clinical
© 2023 by the Society of Nuclear Medicine and Molecular Imaging.