[18F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response
Abstract The growing interest and clinical translation of alpha particle (α) therapies brings with it new challenges to assess target cell engagement and to monitor therapeutic effect. Noninvasive imaging has great potential to guide α-treatment and to harness the potential of these agents in the co...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-17460-0 |
| _version_ | 1818018518505881600 |
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| author | Hanwen Zhang Diane Abou Peng Lu Abbie Meghan Hasson Alexandria Villmer Nadia Benabdallah Wen Jiang David Ulmert Sean Carlin Buck E. Rogers Norman F. Turtle Michael R. McDevitt Brian Baumann Brian W. Simons Farrokh Dehdashti Dong Zhou Daniel L. J. Thorek |
| author_facet | Hanwen Zhang Diane Abou Peng Lu Abbie Meghan Hasson Alexandria Villmer Nadia Benabdallah Wen Jiang David Ulmert Sean Carlin Buck E. Rogers Norman F. Turtle Michael R. McDevitt Brian Baumann Brian W. Simons Farrokh Dehdashti Dong Zhou Daniel L. J. Thorek |
| author_sort | Hanwen Zhang |
| collection | DOAJ |
| description | Abstract The growing interest and clinical translation of alpha particle (α) therapies brings with it new challenges to assess target cell engagement and to monitor therapeutic effect. Noninvasive imaging has great potential to guide α-treatment and to harness the potential of these agents in the complex environment of disseminated disease. Poly(ADP) ribose polymerase 1 (PARP-1) is among the most abundantly expressed DNA repair enzymes with key roles in multiple repair pathways—such as those induced by irradiation. Here, we used a third-generation PARP1-specific radiotracer, [18F]-PARPZ, to delineate castrate resistant prostate cancer xenografts. Following treatment with the clinically applied [225Ac]-PSMA-617, positron emission tomography was performed and correlative autoradiography and histology acquired. [18F]-PARPZ was able to distinguish treated from control (saline) xenografts by increased uptake. Kinetic analysis of tracer accumulation also suggests that the localization of the agent to sites of increased PARP-1 expression is a consequence of DNA damage response. Together, these data support expanded investigation of [18F]-PARPZ to facilitate clinical translation in the ⍺-therapy space. |
| first_indexed | 2024-04-14T07:40:32Z |
| format | Article |
| id | doaj.art-9b792b047c414428bbbdfc607f1aa8a7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-14T07:40:32Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-9b792b047c414428bbbdfc607f1aa8a72022-12-22T02:05:31ZengNature PortfolioScientific Reports2045-23222022-07-011211910.1038/s41598-022-17460-0[18F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy responseHanwen Zhang0Diane Abou1Peng Lu2Abbie Meghan Hasson3Alexandria Villmer4Nadia Benabdallah5Wen Jiang6David Ulmert7Sean Carlin8Buck E. Rogers9Norman F. Turtle10Michael R. McDevitt11Brian Baumann12Brian W. Simons13Farrokh Dehdashti14Dong Zhou15Daniel L. J. Thorek16Department of Radiology, Washington University School of MedicineDepartment of Radiology, Washington University School of MedicineDepartment of Radiology, Washington University School of MedicineDepartment of Radiology, Washington University School of MedicineDepartment of Radiology, Washington University School of MedicineDepartment of Radiology, Washington University School of MedicineProgram in Quantitative Molecular Therapeutics, Washington University School of MedicineJohnsson Comprehensive Cancer Center, University of CaliforniaDepartment of Radiology, University of PennsylvaniaProgram in Quantitative Molecular Therapeutics, Washington University School of MedicineDepartment of Radiology, Washington University School of MedicineDepartment of Radiology, Memorial Sloan Kettering Cancer CenterProgram in Quantitative Molecular Therapeutics, Washington University School of MedicineCenter for Comparative Medicine, Baylor College of MedicineDepartment of Radiology, Washington University School of MedicineDepartment of Radiology, Washington University School of MedicineDepartment of Radiology, Washington University School of MedicineAbstract The growing interest and clinical translation of alpha particle (α) therapies brings with it new challenges to assess target cell engagement and to monitor therapeutic effect. Noninvasive imaging has great potential to guide α-treatment and to harness the potential of these agents in the complex environment of disseminated disease. Poly(ADP) ribose polymerase 1 (PARP-1) is among the most abundantly expressed DNA repair enzymes with key roles in multiple repair pathways—such as those induced by irradiation. Here, we used a third-generation PARP1-specific radiotracer, [18F]-PARPZ, to delineate castrate resistant prostate cancer xenografts. Following treatment with the clinically applied [225Ac]-PSMA-617, positron emission tomography was performed and correlative autoradiography and histology acquired. [18F]-PARPZ was able to distinguish treated from control (saline) xenografts by increased uptake. Kinetic analysis of tracer accumulation also suggests that the localization of the agent to sites of increased PARP-1 expression is a consequence of DNA damage response. Together, these data support expanded investigation of [18F]-PARPZ to facilitate clinical translation in the ⍺-therapy space.https://doi.org/10.1038/s41598-022-17460-0 |
| spellingShingle | Hanwen Zhang Diane Abou Peng Lu Abbie Meghan Hasson Alexandria Villmer Nadia Benabdallah Wen Jiang David Ulmert Sean Carlin Buck E. Rogers Norman F. Turtle Michael R. McDevitt Brian Baumann Brian W. Simons Farrokh Dehdashti Dong Zhou Daniel L. J. Thorek [18F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response Scientific Reports |
| title | [18F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response |
| title_full | [18F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response |
| title_fullStr | [18F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response |
| title_full_unstemmed | [18F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response |
| title_short | [18F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response |
| title_sort | 18f labeled parp 1 pet imaging of psma targeted alpha particle radiotherapy response |
| url | https://doi.org/10.1038/s41598-022-17460-0 |
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