Phase I clinical study of a new radiopharmaceutical based on recombinant target molecules DARPin9_29 labeled with technetium-99m for radionuclide diagnosis of the Her2/neu-positive breast cancer


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Abstract

Introduction. The main attention of researchers is paid to the study of one of the members of the EGFfamily - 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 to 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.

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About the authors

Olga Dmitrievna Bragina

Tomsk National Research Medical Center; National Research Tomsk Polytechnic University

Email: rungis@mail.ru
Cancer Research Institute; PhD, MD, Senior Researcher in Nuclear Medicine Department Kooperativny Str., 5, Tomsk, 634009, Russian Federation; Lenina Avenue, 30, Tomsk, 634050, Russian Federation

Vladimir Ivanovich Chernov

Tomsk National Research Medical Center; National Research Tomsk Polytechnic University

Email: chernov@tnimc.ru
Cancer Research Institute; Dr. Sc. Med., MD, Prof., Head of the Department of Nuclear Medicine Kooperativny Str., 5, Tomsk, 634009, Russian Federation; Lenina Avenue, 30, Tomsk, 634050, Russian Federation

Maria Sergeevna Larkina

National Research Tomsk Polytechnic University; Siberian State Medical University

Email: marialarkina@mail.ru
PhD, Associate Professor, Pharmaceutical Analysis Department Lenina Avenue, 30, Tomsk, 634050, Russian Federation; Moskovsky trakt, 2, Tomsk, 634050, Russian Federation

Elene Sergeevna Stasyuk

National Research Tomsk Polytechnic University

Email: stasyuk@tpu.ru
PhD, researcher Lenina Avenue, 30, Tomsk, 634050, Russian Federation

Roman Vladimirovich Zelchan

Tomsk National Research Medical Center; National Research Tomsk Polytechnic University

Email: r.z.elchan@yandex.ru
Cancer Research Institute; PhD, MD, Senior Researcher in Nuclear Medicine Department Kooperativny Str., 5, Tomsk, 634009, Russian Federation; Lenina Avenue, 30, Tomsk, 634050, Russian Federation

Anna Aleksandrovna Medvedeva

Tomsk National Research Medical Center

Email: medvedeva@tnimc.ru
Cancer Research Institute; PhD, MD, Senior Researcher in Nuclear Medicine Department Kooperativny Str., 5, Tomsk, 634009, Russian Federation

Evgeny Yurievich Garbukov

Tomsk National Research Medical Center

Email: jrmaximum9@gmail.com
Cancer Research Institute; Senior Researcher in General Oncology Department Kooperativny Str., 5, Tomsk, 634009, Russian Federation

Roman Yurievich Vernadskyi

Tomsk National Research Medical Center

Email: vernadskyi@gmail.com
Cancer Research Institute; Junior Researcher in General Oncology Department Kooperativny Str., 5, Tomsk, 634009, Russian Federation

Sergey Mikhailovich Deev

National Research Tomsk Polytechnic University; Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry

Email: biomem@mail.ru
Prof., Head of the Molecular Immunology Laboratory Lenina Avenue, 30, Tomsk, 634050, Russian Federation; Ulitsa Miklukho-Maklaya, 16/10, Moscow, 117997, Russian Federation

Vladimir Maximilianovich Tolmachev

National Research Tomsk Polytechnic University; Uppsala University

Email: vladimir.tolmachev@igp.uu.se
Prof., Head of the Department of Immunology, Genetics and Pathology Lenina Avenue, 30, Tomsk, 634050, Russian Federation; Segerstedthuset, Dag Hammarskjölds väg 7, Uppsala, Sweden

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