Evaluation of maSSS/maSES-PEG2-RM26 for their potential therapeutic use after labeling with Re-188. Could their [99mTc]Tc-labeled counterparts be used to estimate dosimetry?
Abstract Background Gastrin releasing peptide receptor (GRPR)-directed radiopharmaceuticals for targeted radionuclide therapy may be a very promising addition in prostate and breast cancer patient management. Aiming to provide a GRPR-targeting theranostic pair, we have utilized the Tc-99m/Re-188 rad...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-01-01
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| Series: | EJNMMI Radiopharmacy and Chemistry |
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| Online Access: | https://doi.org/10.1186/s41181-024-00326-3 |
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| author | Panagiotis Kanellopoulos Quanyi Yu Abouzayed Abouzayed Ekaterina Bezverkhniaia Vladimir Tolmachev Anna Orlova |
| author_facet | Panagiotis Kanellopoulos Quanyi Yu Abouzayed Abouzayed Ekaterina Bezverkhniaia Vladimir Tolmachev Anna Orlova |
| author_sort | Panagiotis Kanellopoulos |
| collection | DOAJ |
| description | Abstract Background Gastrin releasing peptide receptor (GRPR)-directed radiopharmaceuticals for targeted radionuclide therapy may be a very promising addition in prostate and breast cancer patient management. Aiming to provide a GRPR-targeting theranostic pair, we have utilized the Tc-99m/Re-188 radiometal pair, in combination with two bombesin based antagonists, maSSS-PEG2-RM26 and maSES-PEG2-RM26. The two main aims of the current study were (i) to elucidate the influence of the radiometal-exchange on the biodistribution profile of the two peptides and (ii) to evaluate the feasibility of using the [99mTc]Tc labeled counterparts for the dosimetry estimation for the [188Re]Re-labeled conjugates. Results Both peptides were successfully labeled with Re-188 and evaluated both in vitro and in vivo. In GRPR expressing PC-3 cells, both [188Re]Re-labeled peptides displayed high cellular uptake (8.5 ± 0.1% and 5 ± 0.3% of added activity, respectively), heavily GRPR-driven, while retaining the radioantagonistic profile with slow internalization rates. Both agents demonstrated high receptor affinity when loaded with natRe (7.5 nM and 8 nM, respectively). When tested in vivo in GRPR expressing PC-3 xenografts, both radioantagonists demonstrated high tumor accumulation (6.3 ± 0.5%IA/g and 5 ± 1%IA/g at 1 h pi, respectively), with good retention over time (4 ± 2%IA/g and 3.1 ± 0.1%IA/g at 4 h pi, respectively). In addition, their biodistribution profiles were closely mimicking their [99mTc]Tc-labeled counterparts. Statistically significant lower tumor uptake was found for both conjugates labeled with Tc-99m, which may result in underestimation of the dose delivered to the tumor. Conclusions All the results indicate that Tc-99 m could be used for dosimetry evaluation for the two [188Re]Re-labeled radioligands, with minimal alterations in their biodistribution pattern and tumor targeting capabilities. |
| format | Article |
| id | doaj-art-5a3182ab3ded479ebef6412e123642a8 |
| institution | Kabale University |
| issn | 2365-421X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj-art-5a3182ab3ded479ebef6412e123642a82025-01-19T12:44:05ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2025-01-0110111410.1186/s41181-024-00326-3Evaluation of maSSS/maSES-PEG2-RM26 for their potential therapeutic use after labeling with Re-188. Could their [99mTc]Tc-labeled counterparts be used to estimate dosimetry?Panagiotis Kanellopoulos0Quanyi Yu1Abouzayed Abouzayed2Ekaterina Bezverkhniaia3Vladimir Tolmachev4Anna Orlova5Department of Medicinal Chemistry, Uppsala UniversityDepartment of Medicinal Chemistry, Uppsala UniversityDepartment of Medicinal Chemistry, Uppsala UniversityDepartment of Medicinal Chemistry, Uppsala UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityDepartment of Medicinal Chemistry, Uppsala UniversityAbstract Background Gastrin releasing peptide receptor (GRPR)-directed radiopharmaceuticals for targeted radionuclide therapy may be a very promising addition in prostate and breast cancer patient management. Aiming to provide a GRPR-targeting theranostic pair, we have utilized the Tc-99m/Re-188 radiometal pair, in combination with two bombesin based antagonists, maSSS-PEG2-RM26 and maSES-PEG2-RM26. The two main aims of the current study were (i) to elucidate the influence of the radiometal-exchange on the biodistribution profile of the two peptides and (ii) to evaluate the feasibility of using the [99mTc]Tc labeled counterparts for the dosimetry estimation for the [188Re]Re-labeled conjugates. Results Both peptides were successfully labeled with Re-188 and evaluated both in vitro and in vivo. In GRPR expressing PC-3 cells, both [188Re]Re-labeled peptides displayed high cellular uptake (8.5 ± 0.1% and 5 ± 0.3% of added activity, respectively), heavily GRPR-driven, while retaining the radioantagonistic profile with slow internalization rates. Both agents demonstrated high receptor affinity when loaded with natRe (7.5 nM and 8 nM, respectively). When tested in vivo in GRPR expressing PC-3 xenografts, both radioantagonists demonstrated high tumor accumulation (6.3 ± 0.5%IA/g and 5 ± 1%IA/g at 1 h pi, respectively), with good retention over time (4 ± 2%IA/g and 3.1 ± 0.1%IA/g at 4 h pi, respectively). In addition, their biodistribution profiles were closely mimicking their [99mTc]Tc-labeled counterparts. Statistically significant lower tumor uptake was found for both conjugates labeled with Tc-99m, which may result in underestimation of the dose delivered to the tumor. Conclusions All the results indicate that Tc-99 m could be used for dosimetry evaluation for the two [188Re]Re-labeled radioligands, with minimal alterations in their biodistribution pattern and tumor targeting capabilities.https://doi.org/10.1186/s41181-024-00326-3BombesinTc-99mRe-188AntagonistRadiopharmaceuticalsGRPR |
| spellingShingle | Panagiotis Kanellopoulos Quanyi Yu Abouzayed Abouzayed Ekaterina Bezverkhniaia Vladimir Tolmachev Anna Orlova Evaluation of maSSS/maSES-PEG2-RM26 for their potential therapeutic use after labeling with Re-188. Could their [99mTc]Tc-labeled counterparts be used to estimate dosimetry? EJNMMI Radiopharmacy and Chemistry Bombesin Tc-99m Re-188 Antagonist Radiopharmaceuticals GRPR |
| title | Evaluation of maSSS/maSES-PEG2-RM26 for their potential therapeutic use after labeling with Re-188. Could their [99mTc]Tc-labeled counterparts be used to estimate dosimetry? |
| title_full | Evaluation of maSSS/maSES-PEG2-RM26 for their potential therapeutic use after labeling with Re-188. Could their [99mTc]Tc-labeled counterparts be used to estimate dosimetry? |
| title_fullStr | Evaluation of maSSS/maSES-PEG2-RM26 for their potential therapeutic use after labeling with Re-188. Could their [99mTc]Tc-labeled counterparts be used to estimate dosimetry? |
| title_full_unstemmed | Evaluation of maSSS/maSES-PEG2-RM26 for their potential therapeutic use after labeling with Re-188. Could their [99mTc]Tc-labeled counterparts be used to estimate dosimetry? |
| title_short | Evaluation of maSSS/maSES-PEG2-RM26 for their potential therapeutic use after labeling with Re-188. Could their [99mTc]Tc-labeled counterparts be used to estimate dosimetry? |
| title_sort | evaluation of masss mases peg2 rm26 for their potential therapeutic use after labeling with re 188 could their 99mtc tc labeled counterparts be used to estimate dosimetry |
| topic | Bombesin Tc-99m Re-188 Antagonist Radiopharmaceuticals GRPR |
| url | https://doi.org/10.1186/s41181-024-00326-3 |
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