Abstract
Epidermal growth receptor HER2/neu is still of great interest, the overexpression of which is most often observed in patients with breast cancer and accounts for 15–20 % of cases. Present methods of HER2/neu determination have a number of significant drawbacks. In recent years, alternative framework proteins are used for the targeted radionuclide imaging. Molecules of DARPin (Design Ankyrin Repeat Protein) are one of representatives of scaffolds. Material and methods. The study included 4 breast cancer patients (T1-2N0-1M0) who were not receiving systemic therapy at the time of the study: in 2 patients, HER2/neu overexpression was noted, in 2 patients – not detected. HER2/neu status was determined using an immunohistochemical method and a FISH assay. At the preclinical stage, radiopharmaceutical 99mTc-DARPin9_29 was injected intravenously to all patients, «WholeBody» scintigraphy and single-photon emission computed tomography were performed 2 hours after injection. Results. The distribution of radiopharmaceuticals in organs 2 hours after injection revealed the greatest accumulation in the liver and kidneys. In studying of tumor/background indicator it was revealed that values of the studied parameter in patients with overexpression of HER2 receptors are more than 3 times higher than the values in the subgroup of patients with negative expression of this marker. Conclusion. According to the results of preliminary studies, the 99mTc-DARPin9_29 demonstrated significant differences between tumors with and without HER2/neu overexpression.
Highlights
the overexpression of which is most often observed in patients with breast cancer and accounts
neu determination have a number of significant drawbacks
alternative framework proteins are used for the targeted radionuclide imaging
Summary
Возможности радионуклидной визуализации HER2/neu-позитивного рака молочной железы с использованием радиофармпрепарата на основе рекомбинантных адресных молекул DARPin9_29. До сих пор большой интерес представляет изучение рецептора эпидермального роста HER2/neu, гиперэкспрессия которого наиболее часто отмечается у больных раком молочной железы (РМЖ) (в 15–20 % случаев). В последние годы актуальным для проведения таргетной (направленной) радионуклидной визуализации является применение альтернативных каркасных белков, к одному из которых относится молекула DARPin (Design Ankyrin Repeat Protein). В исследование были включены 4 пациентки с диагнозом РМЖ (T1-2N0-1M0), не получавшие на момент исследования системную терапию: у двух больных отмечалась гиперэкспрессия HER2/neu, у двух экспрессии выявлено не было. Всем больным на этапе диагностики проводились внутривенное введение препарата 99mТс-DARPin9_29 с проведением сцинтиграфии в режиме «WholeBody» и однофотонная эмиссионная компьютерная томография через 2 ч после введения. По результатам предварительных исследований радиофармацевтический препарат 99mTc-DARPin9_29 продемонстрировал существенные различия между больными с гиперэкспрессией и без экспрессии рецептора HER2/neu в опухолевой ткани.
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