Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227
Osteosarcoma is a high-grade sarcoma characterized by osteoid formation, nearly universal expression of IGF1R and with a subset expressing HER-2. These qualities provide opportunities for the use of the alpha particle-emitting isotopes to provide targeted radiation therapy via alpha particles precis...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-11-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.1030094/full |
| _version_ | 1811308574555504640 |
|---|---|
| author | Peter M. Anderson Vivek Subbiah Vivek Subbiah Matteo M. Trucco |
| author_facet | Peter M. Anderson Vivek Subbiah Vivek Subbiah Matteo M. Trucco |
| author_sort | Peter M. Anderson |
| collection | DOAJ |
| description | Osteosarcoma is a high-grade sarcoma characterized by osteoid formation, nearly universal expression of IGF1R and with a subset expressing HER-2. These qualities provide opportunities for the use of the alpha particle-emitting isotopes to provide targeted radiation therapy via alpha particles precisely to bone-forming tumors in addition to IFG1R or Her-2 expressing metastases. This review will detail experience using the alpha emitter radium-223 (223Ra, tradename Xofigo), that targets bone formation, in osteosarcoma, specifically related to patient selection, use of gemcitabine for radio-sensitization, and using denosumab to increasing the osteoblastic phenotype of these cancers. A case of an inoperable left upper lobe vertebral-paraspinal-mediastinal osteoblastic lesion treated successfully with 223Ra combined with gemcitabine is described. Because not all areas of osteosarcoma lesions are osteoblastic, but nearly all osteosarcoma cells overexpress IGF1R, and some subsets expressing Her-2, the anti-IGF1R antibody FPI-1434 linked to actinium-225 (225Ac) or the Her-2 antibody linked to thorium-227 (227Th) may become other means to provide targeted alpha particle therapy against osteosarcoma (NCT03746431 and NCT04147819). |
| first_indexed | 2024-04-13T09:26:44Z |
| format | Article |
| id | doaj.art-7bd2a0d6d3184a758e0f5ba9d4b065fe |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-13T09:26:44Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-7bd2a0d6d3184a758e0f5ba9d4b065fe2022-12-22T02:52:26ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-11-01910.3389/fmed.2022.10300941030094Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227Peter M. Anderson0Vivek Subbiah1Vivek Subbiah2Matteo M. Trucco3Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, Cleveland Clinic Children’s Hospital, Pediatric Institute, Cleveland Clinic, Cleveland, OH, United StatesInvestigational Cancer Therapeutics, Cancer Medicine, Clinical Center for Targeted Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDivision of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pediatric Hematology, Oncology and Bone Marrow Transplant, Cleveland Clinic Children’s Hospital, Pediatric Institute, Cleveland Clinic, Cleveland, OH, United StatesOsteosarcoma is a high-grade sarcoma characterized by osteoid formation, nearly universal expression of IGF1R and with a subset expressing HER-2. These qualities provide opportunities for the use of the alpha particle-emitting isotopes to provide targeted radiation therapy via alpha particles precisely to bone-forming tumors in addition to IFG1R or Her-2 expressing metastases. This review will detail experience using the alpha emitter radium-223 (223Ra, tradename Xofigo), that targets bone formation, in osteosarcoma, specifically related to patient selection, use of gemcitabine for radio-sensitization, and using denosumab to increasing the osteoblastic phenotype of these cancers. A case of an inoperable left upper lobe vertebral-paraspinal-mediastinal osteoblastic lesion treated successfully with 223Ra combined with gemcitabine is described. Because not all areas of osteosarcoma lesions are osteoblastic, but nearly all osteosarcoma cells overexpress IGF1R, and some subsets expressing Her-2, the anti-IGF1R antibody FPI-1434 linked to actinium-225 (225Ac) or the Her-2 antibody linked to thorium-227 (227Th) may become other means to provide targeted alpha particle therapy against osteosarcoma (NCT03746431 and NCT04147819).https://www.frontiersin.org/articles/10.3389/fmed.2022.1030094/fullosteosarcomaosteoblastic metastasesbone metastaseslung metastasesradiosensitizationdenosumab |
| spellingShingle | Peter M. Anderson Vivek Subbiah Vivek Subbiah Matteo M. Trucco Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227 Frontiers in Medicine osteosarcoma osteoblastic metastases bone metastases lung metastases radiosensitization denosumab |
| title | Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227 |
| title_full | Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227 |
| title_fullStr | Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227 |
| title_full_unstemmed | Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227 |
| title_short | Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227 |
| title_sort | current and future targeted alpha particle therapies for osteosarcoma radium 223 actinium 225 and thorium 227 |
| topic | osteosarcoma osteoblastic metastases bone metastases lung metastases radiosensitization denosumab |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.1030094/full |
| work_keys_str_mv | AT petermanderson currentandfuturetargetedalphaparticletherapiesforosteosarcomaradium223actinium225andthorium227 AT viveksubbiah currentandfuturetargetedalphaparticletherapiesforosteosarcomaradium223actinium225andthorium227 AT viveksubbiah currentandfuturetargetedalphaparticletherapiesforosteosarcomaradium223actinium225andthorium227 AT matteomtrucco currentandfuturetargetedalphaparticletherapiesforosteosarcomaradium223actinium225andthorium227 |