Non-invasive HER2 detection in ovarian and breast cancer xenografts with 99m Tc-(HE) 3 Z HER2:V2

Abstract

Abstract Purpose To prepare a HER2 affibody molecular probe with high stability, high labeling yield, and easy radionuclide 99mTc labeling, we performed examinations on the biodistribution, determinated the bioactivity, conducted SPECT static imaging, and used other methods explore the potential of targeted HER2 receptor imaging of SKOV3 ovarian cancer and MDA-MB-361 breast cancer xenografts. Methods Affibody moleculars were produced by genetic recombination expression. The radiochemical purity of the 99mTc labeled HER2 affibody were identified by reverse phase high performance liquid chromatography (RP-HPLC). SKOV3 ovarian cancer cells and MDA-MB-361 breast cancer cells (HER2-positive) were subjected to evaluation of their affinity to HER2 by determining the equilibrium dissociation constants. The biodistribution of the 99mTc-labeled affibody molecular probe was then determined in Balb/c mice bearing SKOV3 tumors. Tumor targeting was assessed in the Balb/c mice using SKOV3, MDA-MB-361 and AT-3 (HER2-negative) xenografts. Results Affibody (HE)3ZHER2:V2 can be obtained by recombinant gene expression, which can be labeled with 99mTc and the radiolabeled molecular probe was identified by RP-HPLC to have a radiochemical purity of 96%. 99mTc-(HE)3ZHER2:V2 using RP-HPLC analysis showed that the radiochemical purity was 96%. The biodistribution study revealed that 99mTc-(HE)3ZHER2:V2 quickly bound to HER2-positive tumors after entering the circulatory system, and was cleared mainly through the urinary system. The HER2-positive SKOV3 and MDA-MB-361 nude mouse model was then subjected to single-photon emission computed tomography (SPECT) imaging 1–3 hours after the administration of an intravenous injection of 99mTc-(HE)3ZHER2:V2 through the tail vein, and the targeted uptake of the molecular probe by the tumor could be seen. Conclusions The molecular probe 99mTc-(HE)3ZHER2:V2 that we prepared in this work can be used to target specifically HER2 for imaging of HER2 positive SKOV3 and MDA-MB-361 xenografts in vivo. It is cleared out from the blood quickly, with no obvious toxic side effects. Therefore, 99mTc-(HE)3ZHER2:V2 is a promising marker for the detection of HER2 expression in tumor cells.