| Added by | JPPOUGET |
|---|---|
| Group name | EquipeJPP |
| Item Type | Journal Article |
| Title | Revisiting the Radiobiology of Targeted Alpha Therapy |
| Creator | Pouget and Constanzo |
| Author | Jean-Pierre Pouget |
| Author | Julie Constanzo |
| Abstract | Targeted alpha therapy (TAT) using alpha particle-emitting radionuclides is in the spotlight after the approval of 223RaCl2 for patients with metastatic castration-resistant prostate cancer and the development of several alpha emitter-based radiopharmaceuticals. It is acknowledged that alpha particles are highly cytotoxic because they produce complex DNA lesions. Hence, the nucleus is considered their critical target, and many studies did not report any effect in other subcellular compartments. Moreover, their physical features, including their range in tissues (<100 ?m) and their linear energy transfer (50-230 keV/?m), are well-characterized. Theoretically, TAT is indicated for very small-volume, disseminated tumors (e.g., micrometastases, circulating tumor cells). Moreover, due to their high cytotoxicity, alpha particles should be preferred to beta particles and X-rays to overcome radiation resistance. However, clinical studies showed that TAT might be efficient also in quite large tumors, and biological effects have been observed also away from irradiated cells. These distant effects are called bystander effects when occurring at short distance (<1 mm), and systemic effects when occurring at much longer distance. Systemic effects implicate the immune system. These findings showed that cells can die without receiving any radiation dose, and that a more complex and integrated view of radiobiology is required. This includes the notion that the direct, bystander and systemic responses cannot be dissociated because DNA damage is intimately linked to bystander effects and immune response. Here, we provide a brief overview of the paradigms that need to be revisited. |
| Publication | Frontiers in Medicine |
| Volume | 8 |
| Pages | 692436 |
| Date | 2021 |
| Journal Abbr | Front Med (Lausanne) |
| Language | eng |
| DOI | 10.3389/fmed.2021.692436 |
| ISSN | 2296-858X |
| Library Catalog | PubMed |
| Extra | PMID: 34386508 PMCID: PMC8353448 |
| Tags | bystander, cGAS-STING, first-last-coresponding, lipid rafts, non-targeted effects, review, targeted alpha particle therapy, targeted alpha radiotherapy |
| Date Added | 2024/12/07 - 07:05:06 |
| Date Modified | 2024/12/07 - 07:15:29 |
| Notes and Attachments | Full Text (Attachment) PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
