Phase I Clinical Study with the GRPR-Antagonist [99mTc]Tc-DB8 for SPECT Imaging of Prostate Cancer: Does the Injected Peptide Mass Make a Difference?
| Parent link: | Pharmaceutics.— .— Basel: MDPI AG Vol. 17, iss. 10.— 2025.— Article number 1323, 20 p. |
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| Other Authors: | , , , , , , , , , , , , , |
| Summary: | Background/Objectives: The gastrin-releasing peptide receptor (GRPR) shows high-density expression in prostate cancer (PCa), especially in the early stages of the disease. The introduction of a safe radiotracer for assessing GRPR-expression in PCa may serve as an alternative or complementary tracer to PSMA-directed probes for patients with insufficient PSMA expression. In the present study, the tolerability and safety, biodistribution, and dosimetry of the new GRPR-targeting radiopeptide [99mTc]Tc-DB8 were investigated for the first time in male PCa patients. A mass escalation study was performed, aiming to improve tumor-to-background contrast and, thereby, to enhance diagnostic accuracy. Methods: Sixteen male patients were enrolled in a single-center diagnostic open-label exploratory Phase I clinical trial. Patients were administered a single intravenous injection of 40, 80, or 120 µg of [99mTc]Tc-DB8 peptide (n = 5–6) and underwent whole-body planar imaging (anterior and posterior) 2, 4, 6, and 24 h post-injection (pi) and SPECT-CT acquisition 2, 4, and 6 h pi. Results: Administration of [99mTc]Tc-DB8 was well tolerated at all tested peptide masses. The effective dose did not differ significantly between the injected peptide mass and was 0.005 ± 0.003 mSv/MBq. High activity uptake was observed in the pancreas and kidneys, which 3-fold decreased with an increasing injected peptide mass from 40 to 120 µg. The activity uptake in primary tumors did not differ significantly between cohorts injected with different peptide masses [SUVmax 1.65–9.96]. The tumor-to-muscle ratios increased with time and were the highest for the cohort injected with 120 µg of peptide, 7.2 ± 3.1 (4.64-11-25) at 4 h pi. Conclusions: Single intravenous administration of [99mTc]Tc-DB8, for visualization of GRPR expression in PCa using SPECT imaging was well tolerated in a peptide mass range of 40–120 µg. An injected peptide mass of 80–120 µg/patient and SPECT acquisition 2–4 h pi were found to be optimal for further clinical studies due to the significantly lower activity accumulation in the pancreas and kidneys Текстовый файл |
| Language: | English |
| Published: |
2025
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| Subjects: | |
| Online Access: | https://doi.org/10.3390/pharmaceutics17101323 |
| Format: | Electronic Book Chapter |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=683076 |
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| 200 | 1 | |a Phase I Clinical Study with the GRPR-Antagonist [99mTc]Tc-DB8 for SPECT Imaging of Prostate Cancer: Does the Injected Peptide Mass Make a Difference? |f Anna Orlova, Anastasia Rybina, Anna Medvedeva [et al.] | |
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| 330 | |a Background/Objectives: The gastrin-releasing peptide receptor (GRPR) shows high-density expression in prostate cancer (PCa), especially in the early stages of the disease. The introduction of a safe radiotracer for assessing GRPR-expression in PCa may serve as an alternative or complementary tracer to PSMA-directed probes for patients with insufficient PSMA expression. In the present study, the tolerability and safety, biodistribution, and dosimetry of the new GRPR-targeting radiopeptide [99mTc]Tc-DB8 were investigated for the first time in male PCa patients. A mass escalation study was performed, aiming to improve tumor-to-background contrast and, thereby, to enhance diagnostic accuracy. Methods: Sixteen male patients were enrolled in a single-center diagnostic open-label exploratory Phase I clinical trial. Patients were administered a single intravenous injection of 40, 80, or 120 µg of [99mTc]Tc-DB8 peptide (n = 5–6) and underwent whole-body planar imaging (anterior and posterior) 2, 4, 6, and 24 h post-injection (pi) and SPECT-CT acquisition 2, 4, and 6 h pi. Results: Administration of [99mTc]Tc-DB8 was well tolerated at all tested peptide masses. The effective dose did not differ significantly between the injected peptide mass and was 0.005 ± 0.003 mSv/MBq. High activity uptake was observed in the pancreas and kidneys, which 3-fold decreased with an increasing injected peptide mass from 40 to 120 µg. The activity uptake in primary tumors did not differ significantly between cohorts injected with different peptide masses [SUVmax 1.65–9.96]. The tumor-to-muscle ratios increased with time and were the highest for the cohort injected with 120 µg of peptide, 7.2 ± 3.1 (4.64-11-25) at 4 h pi. Conclusions: Single intravenous administration of [99mTc]Tc-DB8, for visualization of GRPR expression in PCa using SPECT imaging was well tolerated in a peptide mass range of 40–120 µg. An injected peptide mass of 80–120 µg/patient and SPECT acquisition 2–4 h pi were found to be optimal for further clinical studies due to the significantly lower activity accumulation in the pancreas and kidneys | ||
| 336 | |a Текстовый файл | ||
| 461 | 1 | |t Pharmaceutics |c Basel |n MDPI AG | |
| 463 | 1 | |t Vol. 17, iss. 10 |v Article number 1323, 20 p. |d 2025 | |
| 610 | 1 | |a GRPR | |
| 610 | 1 | |a SPECT | |
| 610 | 1 | |a prostate cancer | |
| 610 | 1 | |a Tc-99m | |
| 610 | 1 | |a molecular imaging | |
| 610 | 1 | |a труды учёных ТПУ | |
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| 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 | |
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| 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 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 | |
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| 701 | |a Tashireva |b L. A. |g Lyubov Aleksandrovna | ||
| 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 Lushnikova |b N. |g Nadejda | |
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| 701 | 1 | |a Nock |b B. A. |g Berthold | |
| 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 | |
| 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 | |
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