Preclinical Evaluation of a Novel High-Affinity Radioligand [<sup>99m</sup>Tc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA)
Radionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a mo...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| author | Ekaterina Bezverkhniaia Panagiotis Kanellopoulos Ayman Abouzayed Mariia Larkina Maryam Oroujeni Anzhelika Vorobyeva Ulrika Rosenström Vladimir Tolmachev Anna Orlova |
| author_facet | Ekaterina Bezverkhniaia Panagiotis Kanellopoulos Ayman Abouzayed Mariia Larkina Maryam Oroujeni Anzhelika Vorobyeva Ulrika Rosenström Vladimir Tolmachev Anna Orlova |
| author_sort | Ekaterina Bezverkhniaia |
| collection | DOAJ |
| description | Radionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a molecule that contains mercaptoacetyl–triglutamate chelator for labeling with Tc-99m (designated as BQ0413). The purpose of this study was to evaluate the imaging properties of [<sup>99m</sup>Tc]Tc-BQ0413. PSMA-transfected PC3-pip cells were used to evaluate the specificity and affinity of [<sup>99m</sup>Tc]Tc-BQ0413 binding in vitro. PC3-pip tumor-bearing BALB/C nu/nu mice were used as an in vivo model. [<sup>99m</sup>Tc]Tc-BQ0413 bound specifically to PC3-pip cells with an affinity of 33 ± 15 pM. In tumor-bearing mice, the tumor uptake of [<sup>99m</sup>Tc]Tc-BQ0413 (38 ± 6 %IA/g in PC3-pip 3 h after the injection of 40 pmol) was dependent on PSMA expression (3 ± 2 %IA/g and 0.9 ± 0.3 %IA/g in PSMA-negative PC-3 and SKOV-3 tumors, respectively). We show that both unlabeled BQ0413 and the commonly used binder PSMA-11 enable the blocking of [<sup>99m</sup>Tc]Tc-BQ0413 uptake in normal PSMA-expressing tissues without blocking the uptake in tumors. This resulted in an appreciable increase in tumor-to-organ ratios. At the same injected mass (5 nmol), the use of BQ0413 was more efficient in suppressing renal uptake than the use of PSMA-11. In conclusion, [<sup>99m</sup>Tc]Tc-BQ0413 is a promising probe for the visualization of PSMA-positive lesions using single-photon emission computed tomography (SPECT). |
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| issn | 1661-6596 1422-0067 |
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| spelling | doaj.art-51889ef7c8134b9fb773186c1f3a3d022023-12-22T14:14:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241739110.3390/ijms242417391Preclinical Evaluation of a Novel High-Affinity Radioligand [<sup>99m</sup>Tc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA)Ekaterina Bezverkhniaia0Panagiotis Kanellopoulos1Ayman Abouzayed2Mariia Larkina3Maryam Oroujeni4Anzhelika Vorobyeva5Ulrika Rosenström6Vladimir Tolmachev7Anna Orlova8Department of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, SwedenDepartment of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, SwedenDepartment of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, SwedenResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634009 Tomsk, RussiaDepartment of Immunology, Genetics and Pathology, Uppsala University, 752 37 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 752 37 Uppsala, SwedenDepartment of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 752 37 Uppsala, SwedenDepartment of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, SwedenRadionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a molecule that contains mercaptoacetyl–triglutamate chelator for labeling with Tc-99m (designated as BQ0413). The purpose of this study was to evaluate the imaging properties of [<sup>99m</sup>Tc]Tc-BQ0413. PSMA-transfected PC3-pip cells were used to evaluate the specificity and affinity of [<sup>99m</sup>Tc]Tc-BQ0413 binding in vitro. PC3-pip tumor-bearing BALB/C nu/nu mice were used as an in vivo model. [<sup>99m</sup>Tc]Tc-BQ0413 bound specifically to PC3-pip cells with an affinity of 33 ± 15 pM. In tumor-bearing mice, the tumor uptake of [<sup>99m</sup>Tc]Tc-BQ0413 (38 ± 6 %IA/g in PC3-pip 3 h after the injection of 40 pmol) was dependent on PSMA expression (3 ± 2 %IA/g and 0.9 ± 0.3 %IA/g in PSMA-negative PC-3 and SKOV-3 tumors, respectively). We show that both unlabeled BQ0413 and the commonly used binder PSMA-11 enable the blocking of [<sup>99m</sup>Tc]Tc-BQ0413 uptake in normal PSMA-expressing tissues without blocking the uptake in tumors. This resulted in an appreciable increase in tumor-to-organ ratios. At the same injected mass (5 nmol), the use of BQ0413 was more efficient in suppressing renal uptake than the use of PSMA-11. In conclusion, [<sup>99m</sup>Tc]Tc-BQ0413 is a promising probe for the visualization of PSMA-positive lesions using single-photon emission computed tomography (SPECT).https://www.mdpi.com/1422-0067/24/24/17391prostate cancerprostate-specific membrane antigenPSMAtechnetium-99mBQ0413single-photon emission computed tomography |
| spellingShingle | Ekaterina Bezverkhniaia Panagiotis Kanellopoulos Ayman Abouzayed Mariia Larkina Maryam Oroujeni Anzhelika Vorobyeva Ulrika Rosenström Vladimir Tolmachev Anna Orlova Preclinical Evaluation of a Novel High-Affinity Radioligand [<sup>99m</sup>Tc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA) International Journal of Molecular Sciences prostate cancer prostate-specific membrane antigen PSMA technetium-99m BQ0413 single-photon emission computed tomography |
| title | Preclinical Evaluation of a Novel High-Affinity Radioligand [<sup>99m</sup>Tc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA) |
| title_full | Preclinical Evaluation of a Novel High-Affinity Radioligand [<sup>99m</sup>Tc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA) |
| title_fullStr | Preclinical Evaluation of a Novel High-Affinity Radioligand [<sup>99m</sup>Tc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA) |
| title_full_unstemmed | Preclinical Evaluation of a Novel High-Affinity Radioligand [<sup>99m</sup>Tc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA) |
| title_short | Preclinical Evaluation of a Novel High-Affinity Radioligand [<sup>99m</sup>Tc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA) |
| title_sort | preclinical evaluation of a novel high affinity radioligand sup 99m sup tc tc bq0413 targeting prostate specific membrane antigen psma |
| topic | prostate cancer prostate-specific membrane antigen PSMA technetium-99m BQ0413 single-photon emission computed tomography |
| url | https://www.mdpi.com/1422-0067/24/24/17391 |
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