JOURNAL DESCRIPTION
The Medical Radiology and Radiation Safety journal ISSN 1024-6177 was founded in January 1956 (before December 30, 1993 it was entitled Medical Radiology, ISSN 0025-8334). In 2018, the journal received Online ISSN: 2618-9615 and was registered as an electronic online publication in Roskomnadzor on March 29, 2018. It publishes original research articles which cover questions of radiobiology, radiation medicine, radiation safety, radiation therapy, nuclear medicine and scientific reviews. In general the journal has more than 30 headings and it is of interest for specialists working in thefields of medicine¸ radiation biology, epidemiology, medical physics and technology. Since July 01, 2008 the journal has been published by State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. The founder from 1956 to the present time is the Ministry of Health of the Russian Federation, and from 2008 to the present time is the Federal Medical Biological Agency.
Members of the editorial board are scientists specializing in the field of radiation biology and medicine, radiation protection, radiation epidemiology, radiation oncology, radiation diagnostics and therapy, nuclear medicine and medical physics. The editorial board consists of academicians (members of the Russian Academy of Science (RAS)), the full member of Academy of Medical Sciences of the Republic of Armenia, corresponding members of the RAS, Doctors of Medicine, professor, candidates and doctors of biological, physical mathematics and engineering sciences. The editorial board is constantly replenished by experts who work in the CIS and foreign countries.
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The two-year impact factor of RISC, according to data for 2017, was 0.439, taking into account citation from all sources - 0.570, and the five-year impact factor of RISC - 0.352.
Medical Radiology and Radiation Safety. 2022. Vol. 67. № 2
THE FIRST EXPERIENCE OF CLINICAL USE 99mTс-DARPinG3 FOR RADIONUCLIDE DIAGNOSIS OF BREAST CANCER WITH HER2/neu OVEREXPRESSION
O.D. Bragina1,2, V.I. Chernov1,2, S.M. Deyev2,4, A.G.Vorobyeva4, E.V. Konovalova3, A.M. Orlova2,4, A.A. Shulga4,
E.Yu. Garbukhov 1, R.V. Zelchan 1,2, A.A. Medvedeva1, V.M. Tolmachev4
1Tomsk National Research Medical Center of Cancer Research Institute, Tomsk, Russia
2 National Research Tomsk Polytechnic University, Tomsk, Russia
3Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
4 Uppsala University, Uppsala, Sweden
Contact person: O.D. Bragina, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: To study the possibility of clinical use of the radiopharmaceutical 99mТс – DARPinG3 for the diagnosis of breast cancer with HER2 / neu overexpression in humans.
Material and methods: The clinical study was registered with ClinicalTrials.gov Identifier: NCT04277338 and approved by the Bioethical Committee of the Research Institute of Oncology of the Tomsk National Research Medical Center. The study included 9 breast cancer patients (T1-4N0-2M0-1) before systemic treatment: 5 – with HER2/neu overexpression; 4 – with negative expression. In all cases, a morphological and immunohistochemical study of the tumor biopsy material was carried out. The dosage of the DARPinG3 protein was 1000 μg; labeling was carried out according to the tricarbonyl technique. WholeBody scintigraphy and single-photon emission computed tomography were performed on an E.CAM 180 gamma camera from Siemens (Germany) at 2, 4, 6 and 24 hours after injection.
Results: The first clinical studies of 99mTc – DARPinG3 at a dosage of 1000 µg demonstrated the safety and the absence of toxic effects on patients with breast cancer. The radiopharmaceutical demonstrated rapid elimination from the bloodstream and an specific effective dose
(0.011 ± 0.001 mSv / MBq), comparable to results of other representatives of alternative scaffold proteins labeled with various isotopes. The highest accumulation of the labeled protein was observed in patients with HER2-positive breast tumors at 2 and 4 hours after injections
(p <0.05, Mann‒Whitney test).
Conclusion: The obtained results indicate that 99mTc-DARPinG3 is safe for clinical use in human and can be considered as a new additional method for diagnosing HER2-positive breast tumors.
Keywords: radionuclide diagnostics, scaffold proteins, DARPinG3, breast cancer, HER2/neu
For citation: Bragina OD, Chernov VI, Deyev SM, Vorobyeva AG, Konovalova EV, Orlova AM, Shulga AA, Garbu-
khov EYu, Zelchan RV, Medvedeva AA, Tolmachev VM. The first experience of clinical use 99mtc-darping3 for radionuclide diagnosis of breast cancer with her2/neu overexpression. Medical Radiology and Radiation Safety. 2022;67(2):38-42. (In Russian) doi: 10.33266/1024-6177-2022-67-2-38-42
References
1. Zavyalova M., Vtorushin S., Krakhmal N., et. al. Clinicopathological Features of Nonspecific Invasive Breast Cancer According to Its Molecular Subtypes. Experimental Oncology. 2016;38;2:122-127
(In Ukr.).
2. Babyshkina N., Malinovskaya E., Cherdinceva N., et. al. Neoadjuvant Chemotherapy for Different Molecular Breast Cancer Subtypes: a Retrospective Study in Russian Population. Medical Oncology. 2014;31;9:1-12.
3. Wolff A.C., Hammond M.E.H., Hicks D.G., et.al. Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. J. Clin. Oncol. 2013;31;3997-4013.
4. Bragina O.D., Chernov V.I., Zelchan R.V., Sinilkin I.IG., Medvedeva A.A., Larkina M.S. Alternative Scaffolds in Radionuclide Diagnosis of Malignancies. Byulleten Sibirskoy Meditsiny – Bulletin of Siberian Medicine. 2019;18;3:125-133 (In Russ.).
5. Shilova O.N., Deyev S.M. DARPins: Promising Scaffolds for Theranostics. Acta Nature. 2019;11;1:42-53 (In Russ.).
6. Bragina O.D., Larkina M.S., Stasyuk E.S., Chernov V.I., Yusubov M.S., Skuridin V.S., et. al. Development of Highly Specific Radiochemical Compounds Based on 99m Tc-Labeled Recombinant Molecules for Targeted Imaging of Cells Overexpressing Her-2/neu. Byulleten Sibirskoy Meditsiny – Bulletin of Siberian Medicine. 2017;16;3:25–33 (In Russ.).
7. Chernov V., Sinilkin I., Choynzonov E., et. al. Comparative Evaluation on 99mTc-Fitat Nanocolloids for Sentinel Lymph Nodes Visualisation in Patients with Cancer of Larynx and Hypopharynx. European Journal of Nuclear Medicine and Molecular Imaging. 2015;42;S1:704.
8. Vorobyeva A., Schulga A., Konovalova E., et. al. Optimal Composition and Position of Histidine-Containing Tags Improves Biodistribution of 99mTc-Labeled DARPin G3. Scientific Reports. 2019;9;1:9405.
9. Bragina O., Chernov V., Schulga A., et. al. Phase I Trial of 99mTc-(HE)3-G3, a DARPin-Based Probe for Imaging of HER2 Expression in Breast Cancer. Journal of Nuclear Medicine. 2021:Jnumed.121.262542. DOI: https://doi.org/10.2967/jnumed.121.262542.
10. Bragina O., Witting E., Garousi J., et. al. Phase I Study of 99mTc-ADAPT6, a Scaffold Protein-Based Probe for Visualization of HER2 Expression in Breast Cancer. Journal of Nuclear Medicine. 2021;62;4:493-499.
11. Bragina O.D., Chernov V.I., Garbukov E.Yu., et. al. Possibilities of Radionuclide Diagnostics of Her2-Positive Breast Cancer Using Technetium-99m-Labeled Target Molecules: the First Experience of Clinical Use. Byulleten sibirskoy meditsiny – Bulletin of Siberian Medicine. 2021;20;1:23-30 (In Russ.).
12. Bragina O.D., Chernov V.I., Tashireva L.A., Zelchan R.V., Medvedeva A.A., Lukina N.M., Goldberg V.E., Tolmachev V.M. Determination of the most Informative Prognostic Parameters for Assessing the Status of the Epidermal Growth Factor Receptor Her2/neu in the Primary Tumor in Breast Cancer Patients Using the Targeted Radiopharmaceutical «99mTс-ADAPT6». Voprosy onkologii – Problems of Oncology. 2021;67;3:368-373 (In Russ.).
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. Article was prepared with equal participation of the authors.
Article received: 30.11.2021. Accepted for publication: 30.03.2022.