Metal-Labeled Aptamers as Novel Nanoprobes for Imaging Mass Cytometry Analysis

Imaging mass cytometry (IMC) is an emerging imaging technology that exploits the multiplexed analysis capabilities of the CyTOF mass cytometer to make spatially resolved measurements for tissue sections. In a comprehensive view of tissue composition and marker distribution, recent developments of IMC require highly sensitive, multiplexed assays. Approaching the sensitivity of the IMC technique, we designed a novel type of biocompatible metal-labeled aptamer nanoprobe (MAP), named ¹⁶⁷Er-A10-3.2. The small molecular probe was synthesized by conjugating ¹⁶⁷Er-polymeric pentetic acid (¹⁶⁷Er-DTPA) with an RNA aptamer A10-3.2. For demonstration, ¹⁶⁷Er-A10-3.2 was applied for observing protein spatial distribution on prostatic epithelium cell of paraffin embedded Prostatic adenocarcinoma (PaC) tissue sections by IMC technology. The ¹⁶⁷Er-A10-3.2 capitalizes on the ability of the aptamer to specifically bind target cancer cells as well as the small size of ¹⁶⁷Er-A10-3.2 can accommodate multiple aptamer binding antigen labeled at high density. The detection signal of ¹⁶⁷Er-A10-3.2 probe was 3-fold higher than that of PSMA antibody probe for a targeted cell under lower temperature epitope retrieval (37 °C) of PaC tissue. Furthermore, we successfully demonstrated the simultaneously staining ability of aptamer probes in IMC analysis. The successful imaging acquisition using aptamers probes in IMC technology may offer opportunity for the diagnosis of malignancies in the future.