Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer
The gastrin-releasing peptide receptor (GRPR) is a promising molecular target for imaging and therapy of prostate cancer using bombesin peptides that bind to the receptor with high affinity. Targeted copper theranostics (TCTs) using copper radionuclides, <sup>64</sup>Cu for imaging and &...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/6/728 |
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| author | Truc T. Huynh Ellen M. van Dam Sreeja Sreekumar Cedric Mpoy Benjamin J. Blyth Fenella Muntz Matthew J. Harris Buck E. Rogers |
| author_facet | Truc T. Huynh Ellen M. van Dam Sreeja Sreekumar Cedric Mpoy Benjamin J. Blyth Fenella Muntz Matthew J. Harris Buck E. Rogers |
| author_sort | Truc T. Huynh |
| collection | DOAJ |
| description | The gastrin-releasing peptide receptor (GRPR) is a promising molecular target for imaging and therapy of prostate cancer using bombesin peptides that bind to the receptor with high affinity. Targeted copper theranostics (TCTs) using copper radionuclides, <sup>64</sup>Cu for imaging and <sup>67</sup>Cu for therapy, offer significant advantages in the development of next-generation theranostics. [<sup>64</sup>Cu]Cu-SAR-BBN is in clinical development for PET imaging of GRPR-expressing cancers. This study explores the therapeutic efficacy of [<sup>67</sup>Cu]Cu-SAR-BBN in a pre-clinical mouse model. The peptide was radiolabeled with <sup>67</sup>Cu, and specific binding of the radiolabeled peptide towards GRPR-positive PC-3 prostate cancer cells was confirmed with 52.2 ± 1.4% total bound compared to 5.8 ± 0.1% with blocking. A therapy study with [<sup>67</sup>Cu]Cu-SAR-BBN was conducted in mice bearing PC-3 tumors by injecting 24 MBq doses a total of six times. Tumor growth was inhibited by 93.3% compared to the control group on day 19, and median survival increased from 34.5 days for the control group to greater than 54 days for the treatment group. The ease and stability of the radiochemistry, favorable biodistribution, and the positive tumor inhibition demonstrate the suitability of this copper-based theranostic agent for clinical assessment in the treatment of cancers expressing GRPR. |
| first_indexed | 2024-03-09T22:46:27Z |
| format | Article |
| id | doaj.art-6b47add857c6406db5f89e77d7494c0d |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:46:27Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-6b47add857c6406db5f89e77d7494c0d2023-11-23T18:27:43ZengMDPI AGPharmaceuticals1424-82472022-06-0115672810.3390/ph15060728Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate CancerTruc T. Huynh0Ellen M. van Dam1Sreeja Sreekumar2Cedric Mpoy3Benjamin J. Blyth4Fenella Muntz5Matthew J. Harris6Buck E. Rogers7Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63108, USAClarity Pharmaceuticals Ltd., Sydney, NSW 2015, AustraliaDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63108, USADepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63108, USACancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, AustraliaCancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, AustraliaClarity Pharmaceuticals Ltd., Sydney, NSW 2015, AustraliaDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63108, USAThe gastrin-releasing peptide receptor (GRPR) is a promising molecular target for imaging and therapy of prostate cancer using bombesin peptides that bind to the receptor with high affinity. Targeted copper theranostics (TCTs) using copper radionuclides, <sup>64</sup>Cu for imaging and <sup>67</sup>Cu for therapy, offer significant advantages in the development of next-generation theranostics. [<sup>64</sup>Cu]Cu-SAR-BBN is in clinical development for PET imaging of GRPR-expressing cancers. This study explores the therapeutic efficacy of [<sup>67</sup>Cu]Cu-SAR-BBN in a pre-clinical mouse model. The peptide was radiolabeled with <sup>67</sup>Cu, and specific binding of the radiolabeled peptide towards GRPR-positive PC-3 prostate cancer cells was confirmed with 52.2 ± 1.4% total bound compared to 5.8 ± 0.1% with blocking. A therapy study with [<sup>67</sup>Cu]Cu-SAR-BBN was conducted in mice bearing PC-3 tumors by injecting 24 MBq doses a total of six times. Tumor growth was inhibited by 93.3% compared to the control group on day 19, and median survival increased from 34.5 days for the control group to greater than 54 days for the treatment group. The ease and stability of the radiochemistry, favorable biodistribution, and the positive tumor inhibition demonstrate the suitability of this copper-based theranostic agent for clinical assessment in the treatment of cancers expressing GRPR.https://www.mdpi.com/1424-8247/15/6/728gastrin-releasing peptide receptorbombesin peptide antagonisttheranosticcopper-67 |
| spellingShingle | Truc T. Huynh Ellen M. van Dam Sreeja Sreekumar Cedric Mpoy Benjamin J. Blyth Fenella Muntz Matthew J. Harris Buck E. Rogers Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer Pharmaceuticals gastrin-releasing peptide receptor bombesin peptide antagonist theranostic copper-67 |
| title | Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer |
| title_full | Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer |
| title_fullStr | Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer |
| title_full_unstemmed | Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer |
| title_short | Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer |
| title_sort | copper 67 labeled bombesin peptide for targeted radionuclide therapy of prostate cancer |
| topic | gastrin-releasing peptide receptor bombesin peptide antagonist theranostic copper-67 |
| url | https://www.mdpi.com/1424-8247/15/6/728 |
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