Imaging Tumor Acidity: pH-Low Insertion Peptide Probe for Optoacoustic Tomography

摘要

Optoacoustic tomography has been used for the detection of pancreatic ductal adenocarcinoma targeted by pH-low insertion peptide (pHLIP) conjugated to near-infrared fluorescent dye. It was proved that tumor targeting is pH dependent. The approach could have major implication for detection and monitoring of pancreatic and other cancers. In this issue of Clinical Cancer Research, Kimbrough and colleagues (1) report that pH-sensitive pHLIP variant 7 (V7) conjugated to near-infrared fluorescent dye, Alexa750, targets pancreatic ductal adenocarcinoma (PDAC) in human S2VP10 and S2013 pancreatic cancer xenograft mouse models with minimal off-target accumulation. At the same time, pH-insensitive K7 pHLIP, where a single protonatable Glu residue was replaced by a positively charged Lys residue, served as a control and showed about 100 times less tumor accumulation. Immediately prior to injection of the constructs, as well as 4 and 24 hours after injection, mice were imaged by using multispectral optoacoustic tomography (MSOT). Optoacoustic imaging is an emerging new technology with the potential to increase sensitivity and improve spatial resolution. It represents a hybrid technique that incorporates advantageous properties of both light and sound, because resolution of the optical contrast obeys the rules of ultrasonic diffraction, rendering photon scattering irrelevant to image resolution (2, 3). Thus, high resolution at depth of organ or tissue could be achieved, in contrast to optical imaging, which is critical for the imaging of tumors in humans.