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
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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.