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Targeted Radioligand Therapy: Physics and Biology, Internal Dosimetry and Other Practical Aspects During 177Lu/225Ac Treatment in Neuroendocrine Tumors and Metastatic Prostate Cancer Publisher Pubmed



Dadgar H1 ; Pashazadeh A2 ; Norouzbeigi N1 ; Assadi M3 ; Albalooshi B4 ; Baum RP5 ; Alibraheem A6 ; Haidar M7 ; Beheshti M8 ; Geramifar P9 ; Vali R10 ; Mohammadi S11 ; Dash S12 ; Malasani V12 Show All Authors
Authors
  1. Dadgar H1
  2. Pashazadeh A2
  3. Norouzbeigi N1
  4. Assadi M3
  5. Albalooshi B4
  6. Baum RP5
  7. Alibraheem A6
  8. Haidar M7
  9. Beheshti M8
  10. Geramifar P9
  11. Vali R10
  12. Mohammadi S11
  13. Dash S12
  14. Malasani V12
  15. Cimini A13
  16. Ricci M14
  17. Esmail AA15
  18. Murad S15
  19. Marafi F16
  20. Treglia G17, 18
  21. Khalaf AN19
  22. Anwar FM19
  23. Usmani S20
  24. Omar Y21
  25. Muhsin H22
  26. Tyurin IE23
  27. Zakhary A23
  28. Alsebaie S24
  29. Cortes DM25
  30. Alhashim M26, 27
  31. Arabi H28
  32. Zaidi H28, 29, 30, 31

Source: Theranostics Published:2025


Abstract

Radioligand therapy (RLT) has garnered significant attention due to the recent emergence of innovative and effective theranostic agents, which showed promising therapeutic and prognostic results in various cancers. Moreover, understanding the interaction between different types of radiation and biological tissues is essential for optimizing therapeutic interventions These concepts directly apply to clinical RLTs and play a crucial role in determining the efficacy and toxicity profile of different radiopharmaceutical agents. Personalized dosimetry is a powerful tool that aids in estimating patient-specific absorbed doses in both tumors and normal organs. Dosimetry in RLT is an area of active investigation, as our current understanding of the relationship between absorbed dose and tissue damage is primarily derived from external-beam radiation therapy. Further research is necessary to comprehensively comprehend this relationship in the context of RLTs. In the present review, we present a thorough examination of the involvement of 177Lu/225Ac radioisotopes in the induction of direct and indirect DNA damage, as well as their influence on the initiation of DNA repair mechanisms in cancer cells of neuroendocrine tumors and metastatic prostate cancer. Current data indicate that high-energy α-emitter radioisotopes can directly impact DNA structure by causing ionization, leading to the formation of ionized atoms or molecules. This ionization process predominantly leads to the formation of irreparable and intricate double-strand breaks (DSBs). On the other hand, the majority of DNA damage caused by β-emitter radioisotopes is indirect, as it involves the production of free radicals and subsequent chemical reactions. Beta particles themselves can also physically interact with the DNA molecule, resulting in single-strand breaks (SSBs) and potentially reversible DSBs. © The author(s).
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