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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

dc.rights.licenseopenen_US
hal.structure.identifierCentre d'Etudes Lasers Intenses et Applications [CELIA]
dc.contributor.authorLAROUZE, Alexandre
hal.structure.identifierCentre d'Etudes Lasers Intenses et Applications [CELIA]
dc.contributor.authorALCOCER AVILA, Mario Enrique
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorMORGAT, Clement
hal.structure.identifierCentre d'Etudes Lasers Intenses et Applications [CELIA]
dc.contributor.authorCHAMPION, Christophe
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorHINDIE, Elif
dc.date.accessioned2023-06-28T12:13:34Z
dc.date.available2023-06-28T12:13:34Z
dc.date.issued2023-06-15
dc.identifier.issn1535-5667en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/183229
dc.description.abstractEnEarly 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. The Monte Carlo code CELLDOSE was used to assess membrane and nuclear absorbed doses from Lu and Tb (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. Tb delivered 2- to 6-fold higher absorbed doses to cell membranes and 2- to 3-fold higher nuclear doses than Lu. 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 Lu (38-41 vs. 4.7-7.2 Gy) and with Tb (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 Lu absorbed dose and 2.9% of the Tb 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 Lu absorbed dose and 10.8% of the Tb 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 Lu and for Tb. Dual targeting was beneficial in minimizing absorbed dose heterogeneities. To eradicate tumor cell clusters, Tb may be a better candidate than Lu. 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 studies.
dc.language.isoENen_US
dc.subject.enTargeted radionuclide therapy
dc.subject.en177Lu
dc.subject.en161Tb
dc.subject.enTerbium-161
dc.subject.enAbsorbed dose
dc.title.enMembrane 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
dc.title.alternativeJ Nucl Meden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.2967/jnumed.123.265509en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed37321819en_US
bordeaux.journalJournal of Nuclear Medicineen_US
bordeaux.volume64en_US
bordeaux.hal.laboratoriesInstitut de neurosciences cognitives et intégratives d'Aquitaine (INCIA) - UMR 5287en_US
bordeaux.issue6en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.teamImagerie multimodale translationnelle
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04145186
hal.version1
hal.date.transferred2023-06-29T04:33:29Z
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Nuclear%20Medicine&rft.date=2023-06-15&rft.volume=64&rft.issue=6&rft.eissn=1535-5667&rft.issn=1535-5667&rft.au=LAROUZE,%20Alexandre&ALCOCER%20AVILA,%20Mario%20Enrique&MORGAT,%20Clement&CHAMPION,%20Christophe&HINDIE,%20Elif&rft.genre=article


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