The Impact of the Injected Mass of the Gastrin-Releasing Peptide Receptor Antagonist on Uptake in Breast Cancer: Lessons from a Phase I Trial of [99mTc]Tc-DB8; Pharmaceutics; Vol. 17, iss. 8
| Parent link: | Pharmaceutics.— .— Basel: MDPI AG Vol. 17, iss. 8.— 2025.— Article number 1000, 20 p. |
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| Andere auteurs: | , , , , , , , , , , , , , |
| Samenvatting: | Title screen Background/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific probes for SPECT would permit imaging-guided therapy in regions with restricted access to PET facilities. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the [99mTc]Tc-DB8 GRPR-antagonistic peptide. We also addressed the important issue of finding the optimal injected peptide mass. Methods: Fifteen female patients with ER-positive primary breast cancer were enrolled and divided into three cohorts receiving [99mTc]Tc-DB8 (corresponding to three distinct doses of 40, 80, or 120 µg DB8) comprising five patients each. Additionally, four patients with ER-negative primary tumors were injected with 80 µg [99mTc]Tc-DB8. The injected activity was 360 ± 70 MBq. Planar scintigraphy was performed after 2, 4, 6, and 24 h, and SPECT/CT scans followed planar imaging 2, 4, and 6 h after injection. Results: No adverse events were associated with [99mTc]Tc-DB8 injections. The effective dose was 0.009–0.014 mSv/MBq. Primary tumors and all known lymph node metastases were visualized irrespective of injected peptide mass. The highest uptake in the ER-positive tumors was 2 h after injection of [99mTc]Tc-DB8 at a 80 µg DB8 dose (SUVmax 5.3 ± 1.2). Injection of [99mTc]Tc-DB8 with 80 µg DB8 provided significantly (p < 0.01) higher uptake in primary ER-positive breast cancer lesions than injection with 40 µg DB8 (SUVmax 2.0 ± 0.3) or 120 µg (SUVmax 3.2 ± 1.4). Tumor-to-contralateral breast ratio after injection of 80 μg was also significantly (p < 0.01, ANOVA test) higher than ratios after injection of other peptide masses. The uptake in ER-negative lesions was significantly lower (SUVmax 2.0 ± 0.3) than in ER-positive tumors. Conclusions: Imaging using [99mTc]Tc-DB8 is safe, tolerable, and associated with low absorbed doses. The tumor uptake is dependent on the injected peptide mass. The injection of an optimal mass (80 µg) provides the highest uptake in ER-positive tumors. At optimal dosing, the uptake was significantly higher in ER-positive than in ER-negative lesions Текстовый файл |
| Taal: | Engels |
| Gepubliceerd in: |
2025
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| Onderwerpen: | |
| Online toegang: | https://doi.org/10.3390/pharmaceutics17081000 |
| Formaat: | Elektronisch Hoofdstuk |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=681848 |
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| 200 | 1 | |a The Impact of the Injected Mass of the Gastrin-Releasing Peptide Receptor Antagonist on Uptake in Breast Cancer: Lessons from a Phase I Trial of [99mTc]Tc-DB8 |f Olga Bragina, Vladimir Chernov, Mariia Larkina [et al.] | |
| 203 | |a Текст |b визуальный |c электронный | ||
| 283 | |a online_resource |2 RDAcarrier | ||
| 300 | |a Title screen | ||
| 320 | |a References: 55 tit | ||
| 330 | |a Background/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific probes for SPECT would permit imaging-guided therapy in regions with restricted access to PET facilities. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the [99mTc]Tc-DB8 GRPR-antagonistic peptide. We also addressed the important issue of finding the optimal injected peptide mass. Methods: Fifteen female patients with ER-positive primary breast cancer were enrolled and divided into three cohorts receiving [99mTc]Tc-DB8 (corresponding to three distinct doses of 40, 80, or 120 µg DB8) comprising five patients each. Additionally, four patients with ER-negative primary tumors were injected with 80 µg [99mTc]Tc-DB8. The injected activity was 360 ± 70 MBq. Planar scintigraphy was performed after 2, 4, 6, and 24 h, and SPECT/CT scans followed planar imaging 2, 4, and 6 h after injection. Results: No adverse events were associated with [99mTc]Tc-DB8 injections. The effective dose was 0.009–0.014 mSv/MBq. Primary tumors and all known lymph node metastases were visualized irrespective of injected peptide mass. The highest uptake in the ER-positive tumors was 2 h after injection of [99mTc]Tc-DB8 at a 80 µg DB8 dose (SUVmax 5.3 ± 1.2). Injection of [99mTc]Tc-DB8 with 80 µg DB8 provided significantly (p < 0.01) higher uptake in primary ER-positive breast cancer lesions than injection with 40 µg DB8 (SUVmax 2.0 ± 0.3) or 120 µg (SUVmax 3.2 ± 1.4). Tumor-to-contralateral breast ratio after injection of 80 μg was also significantly (p < 0.01, ANOVA test) higher than ratios after injection of other peptide masses. The uptake in ER-negative lesions was significantly lower (SUVmax 2.0 ± 0.3) than in ER-positive tumors. Conclusions: Imaging using [99mTc]Tc-DB8 is safe, tolerable, and associated with low absorbed doses. The tumor uptake is dependent on the injected peptide mass. The injection of an optimal mass (80 µg) provides the highest uptake in ER-positive tumors. At optimal dosing, the uptake was significantly higher in ER-positive than in ER-negative lesions | ||
| 336 | |a Текстовый файл | ||
| 461 | 1 | |t Pharmaceutics |c Basel |n MDPI AG | |
| 463 | 1 | |t Vol. 17, iss. 8 |v Article number 1000, 20 p. |d 2025 | |
| 610 | 1 | |a электронный ресурс | |
| 610 | 1 | |a труды учёных ТПУ | |
| 610 | 1 | |a radionuclide molecular imaging | |
| 610 | 1 | |a gastrin-releasing peptide receptor antagonist | |
| 610 | 1 | |a breast cancer | |
| 610 | 1 | |a optimal injected mass | |
| 610 | 1 | |a SPECT | |
| 701 | 1 | |a Bragina |b O. D. |c specialist in the field of medical technology |c Senior Researcher of the Tomsk Polytechnic University, Doctor of Medical Sciences |f 1986- |g Olga Dmitrievna |y Tomsk |9 19084 | |
| 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 |9 17725 | |
| 701 | 1 | |a Larkina |b M. S. |g Mariya Sergeevna |f 1984- |c pharmacist |c Professor; Senior Researcher of the Tomsk Polytechnic University, Doctor of Pharmaceutical Sciences |9 22417 | |
| 701 | 1 | |a Varvashenya |b R. N. |c pharmacist |c engineer at Tomsk Polytechnic University |f 1997- |g Ruslan Nikolaevich |9 88559 | |
| 701 | 1 | |a Zelchan (Zeltchan) |b R. V. |c specialist in the field of medical technology |c Researcher of the Tomsk Polytechnic University, Candidate of Medical Sciences |f 1984- |g Roman Vladimirovich |9 17728 | |
| 701 | 1 | |a Medvedeva |b А. А. |g Anna Aleksandrovna |f 1975- |c specialist in the field of medical technology |c research fellow of Tomsk Polytechnic University, Doctor of Medical Sciences |9 20294 | |
| 701 | 1 | |a Ivanova |b A. |g Anastasia | |
| 701 | 1 | |a Tashireva |b L. A. |g Lyubov Aleksandrovna | |
| 701 | 1 | |a Maina |b T. | |
| 701 | 1 | |a Nock |b B. A. |g Berthold | |
| 701 | 1 | |a Kanellopoulos |b P. |g Panagiotis | |
| 701 | 1 | |a Sorensen |b J. | |
| 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 |9 22212 | |
| 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 |9 22210 | |
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