Development and evaluation of a 99mTc-labeled olaparib analog for PARP imaging
Abstract Background Poly(ADP-ribose) polymerase (PARP) is an important therapeutic target in cancer treatment, and dynamic assessment of its expression level is essential for achieving precision therapy. Although 18F-labeled PARP-targeted radiotracers have demonstrated remarkable tumor-imaging capab...
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SpringerOpen
2025-07-01
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| Series: | EJNMMI Radiopharmacy and Chemistry |
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| Online Access: | https://doi.org/10.1186/s41181-025-00373-4 |
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| author | Wei Xu Junjie Yan Xinlin Zhong Donghui Pan Xinyu Wang Yuping Xu Lizhen Wang Chongyang Chen Min Yang |
| author_facet | Wei Xu Junjie Yan Xinlin Zhong Donghui Pan Xinyu Wang Yuping Xu Lizhen Wang Chongyang Chen Min Yang |
| author_sort | Wei Xu |
| collection | DOAJ |
| description | Abstract Background Poly(ADP-ribose) polymerase (PARP) is an important therapeutic target in cancer treatment, and dynamic assessment of its expression level is essential for achieving precision therapy. Although 18F-labeled PARP-targeted radiotracers have demonstrated remarkable tumor-imaging capabilities in preclinical studies, their high lipophilicity leads to increased non-specific uptake in abdominal organs, which has severely hindered their clinical translation. Furthermore, while PET imaging provides superior resolution and sensitivity, its infrastructure and operational demands may limit widespread accessibility in certain regions. Therefore, the development of SPECT-based PARP radiotracers could offer a complementary approach, potentially expanding access to PARP imaging in a broader range of clinical settings. To provide a more affordable and accessible alternative to PET probes, hydrazinonicotinamide (HYNIC)-olaparib was radiolabeled with technetium-99m (99mTc) and evaluated both in vitro and in vivo using the MDA-MB-453 breast cancer model. Results [99mTc][Tc-HYNIC/EDDA]-olaparib exhibits a high radiochemical yield (> 90%), excellent radiochemical purity (> 90%), and good in vitro stability. The introduction of ethylenediamine-N, N’-diacetic acid (EDDA) and tricine facilitated the synthesis of 99mTc complex, and improved the hydrophilicity (logP = 0.63 ± 0.25) of the probe as well, resulting in reduced the accumulation of radiation in the abdomen. In vitro results indicated that [99mTc][Tc-HYNIC/EDDA]-olaparib could target PRAP-1 in MDA-MB-453 cells. In vivo experiments, micro SPECT/CT imaging provided clear visualization of MDA-MB-453 tumors with significant tumor-to-background distinction, and accumulation of [99mTc][Tc-HYNIC/EDDA]-olaparib was quantified at 3.45 ± 0.17%ID/g at 1 h post intravenous injection. Conclusion These findings suggest that [99mTc][Tc-HYNIC/EDDA]-olaparib holds great promise as a novel radiotracer for PARP imaging. |
| format | Article |
| id | doaj-art-b025a8bc77bf40d093f82558b3e999bc |
| institution | Kabale University |
| issn | 2365-421X |
| language | English |
| publishDate | 2025-07-01 |
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| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj-art-b025a8bc77bf40d093f82558b3e999bc2025-08-20T04:03:12ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2025-07-0110111710.1186/s41181-025-00373-4Development and evaluation of a 99mTc-labeled olaparib analog for PARP imagingWei Xu0Junjie Yan1Xinlin Zhong2Donghui Pan3Xinyu Wang4Yuping Xu5Lizhen Wang6Chongyang Chen7Min Yang8School of Life Sciences and Health Engineering, Jiangnan UniversityNHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear MedicineSchool of Life Sciences and Health Engineering, Jiangnan UniversityNHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear MedicineNHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear MedicineNHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear MedicineNHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear MedicineNHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear MedicineSchool of Life Sciences and Health Engineering, Jiangnan UniversityAbstract Background Poly(ADP-ribose) polymerase (PARP) is an important therapeutic target in cancer treatment, and dynamic assessment of its expression level is essential for achieving precision therapy. Although 18F-labeled PARP-targeted radiotracers have demonstrated remarkable tumor-imaging capabilities in preclinical studies, their high lipophilicity leads to increased non-specific uptake in abdominal organs, which has severely hindered their clinical translation. Furthermore, while PET imaging provides superior resolution and sensitivity, its infrastructure and operational demands may limit widespread accessibility in certain regions. Therefore, the development of SPECT-based PARP radiotracers could offer a complementary approach, potentially expanding access to PARP imaging in a broader range of clinical settings. To provide a more affordable and accessible alternative to PET probes, hydrazinonicotinamide (HYNIC)-olaparib was radiolabeled with technetium-99m (99mTc) and evaluated both in vitro and in vivo using the MDA-MB-453 breast cancer model. Results [99mTc][Tc-HYNIC/EDDA]-olaparib exhibits a high radiochemical yield (> 90%), excellent radiochemical purity (> 90%), and good in vitro stability. The introduction of ethylenediamine-N, N’-diacetic acid (EDDA) and tricine facilitated the synthesis of 99mTc complex, and improved the hydrophilicity (logP = 0.63 ± 0.25) of the probe as well, resulting in reduced the accumulation of radiation in the abdomen. In vitro results indicated that [99mTc][Tc-HYNIC/EDDA]-olaparib could target PRAP-1 in MDA-MB-453 cells. In vivo experiments, micro SPECT/CT imaging provided clear visualization of MDA-MB-453 tumors with significant tumor-to-background distinction, and accumulation of [99mTc][Tc-HYNIC/EDDA]-olaparib was quantified at 3.45 ± 0.17%ID/g at 1 h post intravenous injection. Conclusion These findings suggest that [99mTc][Tc-HYNIC/EDDA]-olaparib holds great promise as a novel radiotracer for PARP imaging.https://doi.org/10.1186/s41181-025-00373-499mTcSPECT imagingPARPOlaparibCancer diagnosis |
| spellingShingle | Wei Xu Junjie Yan Xinlin Zhong Donghui Pan Xinyu Wang Yuping Xu Lizhen Wang Chongyang Chen Min Yang Development and evaluation of a 99mTc-labeled olaparib analog for PARP imaging EJNMMI Radiopharmacy and Chemistry 99mTc SPECT imaging PARP Olaparib Cancer diagnosis |
| title | Development and evaluation of a 99mTc-labeled olaparib analog for PARP imaging |
| title_full | Development and evaluation of a 99mTc-labeled olaparib analog for PARP imaging |
| title_fullStr | Development and evaluation of a 99mTc-labeled olaparib analog for PARP imaging |
| title_full_unstemmed | Development and evaluation of a 99mTc-labeled olaparib analog for PARP imaging |
| title_short | Development and evaluation of a 99mTc-labeled olaparib analog for PARP imaging |
| title_sort | development and evaluation of a 99mtc labeled olaparib analog for parp imaging |
| topic | 99mTc SPECT imaging PARP Olaparib Cancer diagnosis |
| url | https://doi.org/10.1186/s41181-025-00373-4 |
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