A self-triggered radioligand therapy agent for fluorescence imaging of the treatment response in prostate cancer
Purpose Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is emerging as an effective treatment option for metastatic castration-resistant prostate cancer (mCRPC). An imaging-based method to quantify early treatment responses can help to understand and optimize RLT. Methods We developed a self-triggered probe 2 targeting the colocalization of PSMA and caspase-3 for fluorescence imaging of RLT-induced apoptosis. Results The probe binds to PSMA potently with a Ki of 4.12 nM, and its fluorescence can be effectively switched on by caspase-3 with a Km of 67.62 μM. Cellular and in vivo studies demonstrated its specificity for imaging radiation-induced caspase-3 upregulation in prostate cancer. To identify the detection limit of our method, we showed that probe 2 could achieve 1.79 times fluorescence enhancement in response to 177Lu-RLT in a medium PSMA-expressing 22Rv1 xenograft model. Conclusion Probe 2 can potently bind to PSMA, and the fluorescence signal can be sensitively switched on by caspase-3 both in vitro and in vivo. This method may provide an effective tool to investigate and optimize PSMA-RLT..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:49 |
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| Enthalten in: |
European journal of nuclear medicine and molecular imaging - 49(2022), 8 vom: 02. März, Seite 2693-2704 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Hongchuang [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Caspase-3 |
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| Anmerkungen: |
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022 |
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| doi: |
10.1007/s00259-022-05743-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
SPR047328142 |
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| 520 | |a Purpose Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is emerging as an effective treatment option for metastatic castration-resistant prostate cancer (mCRPC). An imaging-based method to quantify early treatment responses can help to understand and optimize RLT. Methods We developed a self-triggered probe 2 targeting the colocalization of PSMA and caspase-3 for fluorescence imaging of RLT-induced apoptosis. Results The probe binds to PSMA potently with a Ki of 4.12 nM, and its fluorescence can be effectively switched on by caspase-3 with a Km of 67.62 μM. Cellular and in vivo studies demonstrated its specificity for imaging radiation-induced caspase-3 upregulation in prostate cancer. To identify the detection limit of our method, we showed that probe 2 could achieve 1.79 times fluorescence enhancement in response to 177Lu-RLT in a medium PSMA-expressing 22Rv1 xenograft model. Conclusion Probe 2 can potently bind to PSMA, and the fluorescence signal can be sensitively switched on by caspase-3 both in vitro and in vivo. This method may provide an effective tool to investigate and optimize PSMA-RLT. | ||
| 650 | 4 | |a Radioligand therapy |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Prostate cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Prostate-specific membrane antigen (PSMA) |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Self-triggered probe |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Caspase-3 |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Wang, Yanpu |4 aut | |
| 700 | 1 | |a Zhang, Jingming |4 aut | |
| 700 | 1 | |a Duan, Xiaojiang |4 aut | |
| 700 | 1 | |a Zhang, Ting |4 aut | |
| 700 | 1 | |a Cai, Xuekang |4 aut | |
| 700 | 1 | |a Ha, Hyunsoo |4 aut | |
| 700 | 1 | |a Byun, Youngjoo |4 aut | |
| 700 | 1 | |a Fan, Yan |4 aut | |
| 700 | 1 | |a Yang, Zhi |4 aut | |
| 700 | 1 | |a Wang, Yiguang |4 aut | |
| 700 | 1 | |a Liu, Zhaofei |4 aut | |
| 700 | 1 | |a Yang, Xing |0 (orcid)0000-0001-5186-4990 |4 aut | |
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