Preparation of Hydrothermal Carbon Quantum Dots as a Contrast Amplifying Technique for the diaCEST MRI Contrast Agents

[Image: see text] The discovery of exogenous contrast agents (CAs) is one of the key factors behind the success and widespread acceptability of MRI as an imaging tool. To the long list of CAs, the newest addition is the chemical exchange saturation transfer (CEST)-based CAs. Among them, the diaCEST CAs are the safer metal-free option constituted by a large pool of organic and macromolecules, but the tradeoff comes in terms of smaller natural offset. Another major challenge for the CEST CAs is that they need to operate in the tens of millimolar concentration range to produce any meaningful contrast. The quest for high efficiency diaCEST agents has led to a number of strategies such as use of hydrogen bonding, use of equivalent protons, and use of diatropic ring current. Here, we present carbon quantum dot formation using hydrothermal treatment as a new strategy to amplify diaCEST contrast efficiency. We show that while the well-known analgesic drug lidocaine hydrochloride when repurposed as a diaCEST CA produces no contrast at the physiological pH and temperature, the carbon dots prepared from it elevate the physiological contrast to a sizable 11%. Also, the maximum efficiency at an acidic pH gets amplified by a factor of 2 to 46%. The study showed that the enhancement in CEST efficiency is reproducible and the pH response of these carbon dots is tunable through variation in synthesis conditions such as temperature, duration, and precursor concentration.