review · Theranostics
Targeted radioligand therapy has become an important approach for managing various cancers, including neuroendocrine tumours and metastatic prostate cancer. Optimising these therapies requires an understanding of how distinct types of radiation interact with biological tissues to influence both treatment efficacy and toxicity. While patient-specific dosimetry helps estimate absorbed radiation doses in tumours and healthy organs, current models still rely heavily on findings from external-beam radiation therapy rather than radioligand therapy. Evidence shows that high-energy alpha-emitting radioisotopes such as actinium-225 cause direct DNA ionisation, leading to complex and largely irreparable double-strand breaks. In contrast, beta-emitting radioisotopes like lutetium-177 mainly produce indirect DNA damage via free radical formation, resulting in single-strand breaks and potentially reversible double-strand breaks.
Targeted radioligand therapy offers promising ways to treat advanced cancers by delivering radiation directly to tumours. Understanding precisely how alpha and beta emitters damage cancer DNA, alongside improving personalised radiation measurements, helps clinicians design safer treatments that destroy tumours effectively while sparing healthy organs from harmful side effects.
The abstract does not indicate a direct commercialisation pathway, as it provides a review of the physical, biological, and dosimetric mechanisms underpinning actinium-225 and lutetium-177 therapies rather than a specific product or commercial pipeline.
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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 IvyspringInternational Publisher 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 177 Lu/ 225 Ac 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 -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 -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.
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DOI: 10.7150/thno.107963
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