Preclinical Evaluation of 99mTc-Labeled GRPR Antagonists maSSS/SES-PEG2-RM26 for Imaging of Prostate Cancer; Pharmaceutics; Vol. 13, iss. 2
| Parent link: | Pharmaceutics Vol. 13, iss. 2.— 2021.— [182, 14 p.] |
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| Körperschaft: | |
| Weitere Verfasser: | , , , , , , |
| Zusammenfassung: | Title screen Background: Gastrin-releasing peptide receptor (GRPR) is an important target for imaging of prostate cancer. The wide availability of single-photon emission computed tomography/computed tomography (SPECT/CT) and the generator-produced 99mTc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers. Methods: Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG2-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PEG2-RM26 (RM26 = d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) were radiolabeled with 99mTc and characterized in vitro using PC-3 cells and in vivo, using NMRI or PC-3 tumor bearing mice. SPECT/CT imaging and dosimetry calculations were performed for [99mTc]Tc-maSSS-PEG2-RM26. Results: Peptides were radiolabeled with high yields (>98%), demonstrating GRPR specific binding and slow internalization in PC-3 cells. [99mTc]Tc-maSSS-PEG2-RM26 outperformed [99mTc]Tc-maSES-PEG2-RM26 in terms of GRPR affinity, with a lower dissociation constant (61 pM vs 849 pM) and demonstrating higher tumor uptake. [99mTc]Tc-maSSS-PEG2-RM26 had tumor-to-blood, tumor-to-muscle, and tumor-to-bone ratios of 97 ± 56, 188 ± 32, and 177 ± 79, respectively. SPECT/CT images of [99mTc]Tc-maSSS-PEG2-RM26 clearly visualized the GRPR-overexpressing tumors. The dosimetry estimated for [99mTc]Tc-maSSS-PEG2-RM26 showed the highest absorbed dose in the small intestine (1.65•10-3 mGy/MBq), and the effective dose is 3.49•10-3 mSv/MBq. Conclusion: The GRPR antagonist maSSS-PEG2-RM26 is a promising GRPR-targeting agent that can be radiolabeled through a single-step with the generator-produced 99mTc and used for imaging of GRPR-expressing prostate cance. |
| Sprache: | Englisch |
| Veröffentlicht: |
2021
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| Schlagworte: | |
| Online-Zugang: | https://doi.org/10.3390/pharmaceutics13020182 |
| Format: | Elektronisch Buchkapitel |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=665210 |
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| 200 | 1 | |a Preclinical Evaluation of 99mTc-Labeled GRPR Antagonists maSSS/SES-PEG2-RM26 for Imaging of Prostate Cancer |f A. Abouzayed, S. S. Rinne, S. Hamideh [et al.] | |
| 203 | |a Text |c electronic | ||
| 300 | |a Title screen | ||
| 320 | |a [References: 45 tit.] | ||
| 330 | |a Background: Gastrin-releasing peptide receptor (GRPR) is an important target for imaging of prostate cancer. The wide availability of single-photon emission computed tomography/computed tomography (SPECT/CT) and the generator-produced 99mTc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers. Methods: Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG2-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PEG2-RM26 (RM26 = d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) were radiolabeled with 99mTc and characterized in vitro using PC-3 cells and in vivo, using NMRI or PC-3 tumor bearing mice. SPECT/CT imaging and dosimetry calculations were performed for [99mTc]Tc-maSSS-PEG2-RM26. Results: Peptides were radiolabeled with high yields (>98%), demonstrating GRPR specific binding and slow internalization in PC-3 cells. [99mTc]Tc-maSSS-PEG2-RM26 outperformed [99mTc]Tc-maSES-PEG2-RM26 in terms of GRPR affinity, with a lower dissociation constant (61 pM vs 849 pM) and demonstrating higher tumor uptake. [99mTc]Tc-maSSS-PEG2-RM26 had tumor-to-blood, tumor-to-muscle, and tumor-to-bone ratios of 97 ± 56, 188 ± 32, and 177 ± 79, respectively. SPECT/CT images of [99mTc]Tc-maSSS-PEG2-RM26 clearly visualized the GRPR-overexpressing tumors. The dosimetry estimated for [99mTc]Tc-maSSS-PEG2-RM26 showed the highest absorbed dose in the small intestine (1.65•10-3 mGy/MBq), and the effective dose is 3.49•10-3 mSv/MBq. Conclusion: The GRPR antagonist maSSS-PEG2-RM26 is a promising GRPR-targeting agent that can be radiolabeled through a single-step with the generator-produced 99mTc and used for imaging of GRPR-expressing prostate cance. | ||
| 461 | |t Pharmaceutics | ||
| 463 | |t Vol. 13, iss. 2 |v [182, 14 p.] |d 2021 | ||
| 610 | 1 | |a электронный ресурс | |
| 610 | 1 | |a труды учёных ТПУ | |
| 610 | 1 | |a prostate cancer | |
| 610 | 1 | |a gastrin-releasing peptide receptor antagonist | |
| 610 | 1 | |a technetium-99m | |
| 610 | 1 | |a singlephoton emission computed tomography | |
| 610 | 1 | |a RM26 | |
| 610 | 1 | |a рак | |
| 610 | 1 | |a технеций-99m | |
| 610 | 1 | |a компьютерная томография | |
| 610 | 1 | |a визуализация | |
| 701 | 1 | |a Abouzayed |b A. |g Ayman | |
| 701 | 1 | |a Rinne |b S. S. |g Sara | |
| 701 | 1 | |a Hamideh |b S. |g Sabahnoo | |
| 701 | 1 | |a Sorensen |b J. |g Jens | |
| 701 | 1 | |a Chernov |b V. I. |c specialist in the field of medical technology |c lead engineer of Tomsk Polytechnic University, doctor of medical sciences |f 1962- |g Vladimir Ivanovich |3 (RuTPU)RU\TPU\pers\34191 |9 17725 | |
| 701 | 1 | |a Tolmachev |b V. M. |c specialist in the field of medical technology |c Director of the Research Center "Oncoteranostika", Tomsk Polytechnic University, Ph.D |f 1961- |g Vladimir Maksimilianovich |3 (RuTPU)RU\TPU\pers\46552 |9 22210 | |
| 701 | 1 | |a Orlova |b A. M. |c specialist in the field of medical technology |c Senior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D |f 1960- |g Anna Markovna |3 (RuTPU)RU\TPU\pers\46554 |9 22212 | |
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| 856 | 4 | |u https://doi.org/10.3390/pharmaceutics13020182 | |
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