Molecular imaging of HER2-positive tumors via a target-specific 18F-labeled aptamer

Abstract

Purpose

Aptamers are single-stranded oligonucleotides that bind to a target molecule with high affinity and specificity. In this study, we undertook to evaluate the target specificity and applicability for in vivo molecular imaging of an aptamer labeled with a radioisotope.

Methods

The human epidermal growth factor receptor 2 (HER2/ErbB2) aptamer was radiolabeled with 18F. HER2-positive tumor cell uptake of aptamer was evaluated in comparison with negative controls by flow cytometry and confocal microscopy. Using 18F-labeled HER2-specific aptamer positron emission tomography (PET), in vivo molecular images of BT474 tumor-bearing mice were taken at each time point.

Results

In flow cytometric analysis, HER2 aptamer showed strong binding to HER2-positive BT474 cells, while binding to HER2-negative MDA-MB231 cells was quite low. Likewise, in confocal microscopic images, the aptamer was seen to bind to HER2-positive breast cancer cells, with minimal binding to HER2-negative cells. In vivo PET molecular imaging of BT474 tumor-bearing mice showed that uptake of the 18F-labeled HER2 specific aptamer into the tumor was significantly increased. HER2 aptamer was able to preferentially bind to HER2-positive breast cancer cells both in vitro and in vivo, possibly by recognizing HER2 structure on the surface of these cells.

Conclusions

18F-labeled aptamer enabled appropriate visualization of HER2 expression by human breast cancer cells. The results suggest that radiolabeled HER2 aptamer may have potential applications in determining treatment strategies or in applying targeted therapy against HER2-positive breast cancer cells.