PHASE I CLINICAL STUDY OF A NEW RADIOPHARMACEUTICAL BASED ON RECOMBINANT TARGET MOLECULES DARPIN9_29 LABELED WITH 99mTECHNETIUM FOR RADIONUCLIDE DIAGNOSIS OF THE Her2/neu-POSITIVE BREAST CANCER

DOI: https://doi.org/10.29296/24999490-2021-02-06

O.D. Bragina(1, 2), V.I. Chernov(1, 2), M.S. Larkina(2, 5), E.S. Stasyuk(2), R.V. Zelchan(1, 2), A.A. Medvedeva(1), E.Yu. Garbukov(1), R.Yu. Vernadskyi(1), S.M. Deev(2, 3), V.M. Tolmachev(2, 4) 1-Cancer Research Institute, Tomsk National Research Medical Center, Kooperativny Str., 5, Tomsk, 634009, Russian Federation; 2-National Research Tomsk Polytechnic University, Lenina Avenue, 30, Tomsk, 634050, Russian Federation; 3-Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Ulitsa Miklukho-Maklaya, 16/10, Moscow, 117997, Russian Federation; 4-Uppsala University, Segerstedthuset, Dag Hammarskjölds väg 7, Uppsala, Sweden; 5-Siberian State Medical University, Moskovsky trakt, 2, Tomsk, 634050, Russian Federation E-mail: rungis@mail.ru

Introduction. The main attention of researchers is paid to the study of one of the members of the EGF family – the receptor of epidermal growth factor 2 (Her2/neu), the overexpression of which is detected in 15–20% of cases of invasive breast cancer and had an unfavorable prognosis and an aggressive process. In recent years, alternative scaffold proteins are used for the targeted radionuclide imaging. Molecules of DARPin (Design Ankyrin Repeat Protein) are one of the representatives of scaffolds. The aim of the study. Assessment of the clinical use of a new radiopharmaceutical 99mTc-DARPin9_29 for the diagnosis of breast cancer with overexpression of Her2/neu in humans. Methods. The study included 12 breast cancer patients (T1-4N0-2M0): in 6 patients, Her2/neu overexpression was noted, in 6 patients – not detected. At the preclinical stage, all patients underwent morphological and immunohistochemical studies of the primary tumor biopsy material. 99mTc-DARPin9_29 was injected intravenously before therapy, WholeBody scintigraphy and SPECT were performed 2, 4, 6, and 24 hours after injection. Results. The distribution of radiopharmaceuticals in organs revealed the greatest accumulation in the liver and kidneys, adrenal glands, and spleen. The half-life elimination from blood was 2.51 hours. In studying tumor/background index, values of the studied parameter in patients with overexpression of Her2 receptors were revealed tо be more than by 2.5 times higher than the values in the subgroup of patients with negative expression of this marker. Conclusion. The radiopharmaceutical 99mTc-DARPin9_29 may be considered as a new additional method for Her2-positive breast tumors diagnosis.
Keywords: 
breast cancer, DARPin9_29, target radionuclide diagnostics

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