CEST theranostics: label-free MR imaging of anticancer drugs

// Yuguo Li 1,2,* , Hanwei Chen 2,3,4,* , Jiadi Xu 1,2 , Nirbhay N. Yadav 1,2 , Kannie W. Y. Chan 1,2 , Liangping Luo 4 , Michael T. McMahon 1,2 , Bert Vogelstein 5 , Peter C.M. van Zijl 1,2 , Shibin Zhou 5 and Guanshu Liu 1,2 1 F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA 2 The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 3 Department of Radiology, Panyu Central Hospital, Guangzhou, China 4 Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, China 5 Ludwig Center, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA * These authors have contributed equally to this work Correspondence to: Guanshu Liu, email: // Keywords : CEST, MRI, theranostics, image-guided drug delivery, chemotherapy Received : November 01, 2015 Accepted : January 28, 2016 Published : February 02, 2016 Abstract Image-guided drug delivery is of great clinical interest. Here, we explored a direct way, namely CEST theranostics, to detect diamagnetic anticancer drugs simply through their inherent Chemical Exchange Saturation Transfer (CEST) MRI signal, and demonstrated its application in image-guided drug delivery of nanoparticulate chemotherapeutics. We first screened 22 chemotherapeutic agents and characterized the CEST properties of representative agents and natural analogs in three major categories, i.e., pyrimidine analogs, purine analogs, and antifolates, with respect to chemical structures. Utilizing the inherent CEST MRI signal of gemcitabine, a widely used anticancer drug, the tumor uptake of the i.v.-injected, drug-loaded liposomes was successfully detected in CT26 mouse tumors. Such label-free CEST MRI theranostics provides a new imaging means, potentially with an immediate clinical impact, to monitor the drug delivery in cancer.