Microdosimetry assessment of the radiochemical element 177Lu in the treatment of metastatic prostate cancer of the LNCaP cell line
Abstract
Objective: The aim of our study is to optimize the dose to develop a new treatment protocol for prostate cancer with 177Lu in order to reduce the irradiation of surrounding organs at risk.
Methods: A cell line, LNCaP, was used as a target for 177Lu irradiation at the cellular level. A simple linear quadratic model implemented in the MIRDcell software was chosen to describe the survival probability of cancer cells.
Results: Our model was established with an activity range per cell of 0.01 to 0.62 Bq/cell corresponding to an absorbed dose of 2 to 125 Gy respectively. However, 0.3 Bq/cell approximately 62 Gy seemed to be the most acceptable planning as it corresponds to 7.4 GBq/cycle, the typical value delivered at 100% of tumor cell coverage. Indeed, a cellular energy distribution yields a self-dose of S(N<--N) = 1.35E-03 Gy/Bq·s, indicating that the nucleus absorbs more energy. Cellular absorption is much lower than that of the nucleus, with S (C<--C) = 1.68E-04 Gy/Bq·s. A portion of the energy is deposited in the cytoplasm, and energy is transferred between the cytoplasm and the nucleus, with S (N <--Cy) = S (Cy<--N) = 1.30E-04 Gy/Bq·s. The membrane cell contributes less to the cellular dose, with S(N<--CS) = 1.30E-04 Gy/Bq·s.
Conclusion: This study shows the necessity of a personalized pre-treatment dosimetry to deliver an optimal lethal dose to tumor cells.
Keywords: LNCaP cell line, 177Lu, linear quadratic, MIRDcell
Keywords:
LNCaP cell line, 177Lu, linear quadratic, MIRDcellDOI
https://doi.org/10.22270/jddt.v15i8.7292References
1. Erra B, Pradere B. Place de la médecine nucléaire au sein de la prise en charge du cancer de la prostate Nuclear medicine for prostate cancer management. Progrès en urologie 2019;29:S2-S7 https://doi.org/10.1016/S1166-7087(19)30165-4 PMid:31307627
2. Umbricht CA, Benešová M, Schmid RM, et al. 44Sc-PSMA-617 for radiotheragnostics in tandem with 177Lu-PSMA-617-preclinical investigations in comparison with 68Ga-PSMA-11 and 68Ga-PSMA-617. EJNMMI Res. 2017; 7:9. https://doi.org/10.1186/s13550-017-0257-4 PMid:28102507 PMCid:PMC5247395
3. Umbricht CA, Koster U, Bernhardt P, et al. Alpha-PET for Prostate Cancer: Preclinical investigation using 149Tb-PSMA-617. Sci Rep. 2019 ;9:17800. https://doi.org/10.1038/s41598-019-54150-w PMid:31780798 PMCid:PMC6882876
4. La lutte contre le cancer intensifiée grâce au SCK CEN et à l'IRE. https://www.ire.eu/public/media-room/la-lutte-contre-le-cancer-intensifiee-grace-au-sck-cen-et-a-lire. Consulted the 20/06/2024
5. NZAMBA Bisselou Paul Ludovic, ODO Bitti Addé, NZIENGUI Tirogo Christian, KOUASSI Kouamé Konan Yvon, KAGAMBEGA Zoewendbem Arsène Gaetan, TOURE Moctar. Prostate cancer in black subjects in Ivory Coast Prostate cancer in black subjects in Côte d'Ivoire. Rev int sc méd Abj. RISM 2021;23(1):49-54.
6. National Cancer Control Program (PNLcaP) of the Ministry of Health, Public Hygiene and Universal Health Coverage of the Republic of côte d'ivoire.
7. https://www.pnlca.org/copy-of-cancer-en-cote-d-voire-2. Consulted the 04/07/2024
8. Elisa Mattar and Nicole Jawerth. Office of Public Information and Communication. IAEA Bulletin. See and Kill Cancer Cells. https://www.iaea.org/fr/newscenter/news/voir-et-tuer-les-cellules-cancereuses. Consulted the 04/07/2024
9. Jabbari M and Pandesh S. Monte carlo investigation of S values for 111In radionuclide therapy. Braz. J. Rad. Sci. 11-04(2023) 01-12, e2348. https://doi.org/10.15392/2319-0612.2023.2348
10. Vaziri B, Wu H, Dhawan AP, Du P, Howell RW. MIRD Pamphlet No. 25: MIRDcell V2.0 Software Tool for Dosimetric Analysis of Biologic Response of Multicellular Populations. J Nucl Med. 2014 Sep;55(9):1557-64. https://doi.org/10.2967/jnumed.113.131037 PMid:25012457
11. Katugampola S, Wang J, Rosen A, et al. MIRD Pamphlet No. 27: MIRDcell V3, a revised software tool for multicellular dosimetry and bioeffect modeling. J Nucl Med. 2022;63:1441-1449. https://doi.org/10.2967/jnumed.121.263253 PMid:35145016 PMCid:PMC9454469
12. Katugampola S, Wang J, Howell RW. MIRD Pamphlet No. 30: MIRDcell V4, Artificial intelligence tools to formulate optimized radiopharmaceutical cocktails for therapy. J Nucl Med. submitted.
13. Chan HS, de Blois E, Morgenstern A, Bruchertseifer F, de Jong M, Breeman W, et al. In Vitro comparison of 213Bi- and 177Lu-radiation for peptide receptor radionuclide therapy. PLoS ONE 2017;12(7):e0181473. https://doi.org/10.1371/journal.pone.0181473 PMid:28732021 PMCid:PMC5521788
14. Loubeau G. Impact of nucleophosmin protein (NPM1) overexpression on prostate cancer progression. Agricultural Sciences. University Blaise Pascal - Clermont-Ferrand II, 2012. France. ffNNT : 2012CLF22319ff. fftel-00870415f
15. Kratochwil C, Fendler WP, Eiber M, Baum R, Bozkurt MF, Czernin J, et al. EANM procedure guidelines for radionuclide therapy with 177Lu-labelled PSMA-ligands (177Lu-PSMA RLT). Eur J Nucl Med Mol Imaging. 2019 46:2536-44. https://doi.org/10.1007/s00259-019-04485-3 PMid:31440799
16. Borgna F et al. "Combination of terbium-161 with somatostatin receptor antagonists-a potential paradigm shift for the treatment of neuroendocrine neoplasms". In: European journal of nuclear medicine and molecular imaging 2021;1-14. https://doi.org/10.1007/s00259-021-05564-0 PMid:34625828 PMCid:PMC8921065
17. Howell RW, Rajon D, Bolch WE. Monte Carlo simulation of irradiation and killing in three-dimensional cell populations with lognormal cellular uptake of radioactivity. Int J Radiat Biol. 2012; 88:115-122. https://doi.org/10.3109/09553002.2011.602379 PMid:21745001 PMCid:PMC4029158
18. Goddu SM, Howell RW, Rao DV. Cellular dosimetry: absorbed fractions for monoenergetic electron and alpha particle sources and S-values for radionuclides uniformly distributed in different cell compartments. J Nucl Med. 1994; 35:303-316.
19. Maria Anthi Kouri, Anastasios Georgopoulos , George E Manios , Eirini Maratou , Aris Spathis , Sofia Chatziioannou , Kalliopi Platoni , Efstathios P Efstathopoulos. Preliminary Study on Lutetium-177 and Gold Nanoparticles: Apoptosis and Radiation Enhancement in Hepatic Cancer Cell Line. Curr Issues Mol Biol. 2024 Oct 30;46(11):12244-12259. https://doi.org/10.3390/cimb46110727 PMid:39590321 PMCid:PMC11592690
20. Eberlein U, Nowak C, Bluemel C, Buck AK, Werner RA, Scherthan H, Lassmann M, DNA damage in blood lymphocytes in patients after (177)Lu peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2015 Oct;42(11):1739-1749. https://doi.org/10.1007/s00259-015-3083-9 PMid:26048612 PMCid:PMC4554740
21. . Monfared YK, Heidari P, Klempner SJ, Mahmood U, Parikh AR, Hong TS, Strickland MR, Esfahani SA, DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair. Pharmaceutics. 2023 Dec 12;15(12):2761. https://doi.org/10.3390/pharmaceutics15122761 PMid:38140100 PMCid:PMC10748326
22. Luna-Gutiérrez M, Azorín-Vega E, Oros-Pantoja R, Ocampo-García B, Cruz-Nova P, Jiménez-Mancilla N, Bravo-Villegas G, Santos-Cuevas C, Meléndez-Alafort L, Ferro-Flores G. Lutetium-177 labeled iPD-L1 as a novel immunomodulator for cancer-targeted radiotherapy. EJNMMI Radiopharm Chem. 2025 Jan 22;10(1):5. https://doi.org/10.1186/s41181-025-00328-9 PMid:39843795 PMCid:PMC11754567
23. Murthy V, Voter AF, Nguyen K, Allen-Auerbach M, Chen L, Caputo S, Ledet E, Akerele A, Tuchayi AM, Lawhn-Heath C, Wang T, Carducci MA, Pomper MG, Paller CJ, Czernin J, Solnes LB, Hope TA, Sartor O, Calais J, Gafita A. Efficacy and Toxicity of [177Lu] Lu-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: Results from the U.S. Expanded-Access Program and Comparisons with Phase 3 VISION Data. J Nucl Med 2024; 65:1740-1744. https://doi.org/10.2967/jnumed.124.267816 PMid:39327018
24. Sartor O, de Bono J, Chi KN. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. NEnglJMed. 2021;385:1091-1103. https://doi.org/10.1056/NEJMoa2107322 PMid:34161051 PMCid:PMC8446332
25. Nardo GLD. Concepts in radioimmunotherapy and immunotherapy: Radioimmunotherapy from a Lym-1 perspective Semin Oncol. 2005 Feb; 32 (1suppl1): S27-35. https://doi.org/10.1053/j.seminoncol.2005.01.011 PMid:15786023
26. Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Radiopharmaceutical therapy in cancer: clinical advances and challenges Nat Rev Drug Discov 2020;19:589-608 https://doi.org/10.1038/s41573-020-0073-9 PMid:32728208 PMCid:PMC7390460
27. Tranel J, Palm S, Graves SA, Feng FY, Hope TA. Impact of radiopharmceutical therapy (177Lu, 225Ac) microdistribution in a cancer associated fibroblasts model. EJNMMI Phys. 2022 Sep 30;9(1):67. https://doi.org/10.1186/s40658-022-00497-5 PMid:36178531 PMCid:PMC9525486
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