Development of Gadolinium Based Contrast Agents to Detect Tumor Apoptosis in vivo using MRI
Neves A, Kettunen M, Hu D, Brindle K, de Backer M, Krishnan A
University of Cambridge
The C2A domain of Synaptotagmin I (C2A) shows high affinity binding to phosphatidylserine on apoptotic cells. We are developing Gd3+-based contrast agents (CA), based on conjugation of C2A. GST-tagged C2A directly conjugated to a Gd-DTPA complex produced a CA with a T1-relaxivity of 60 mM-1s-1 (9.4T). Experiments in vitro, showed an increase in signal intensity in T1-weighted images with increasing amounts of C2A-GST-Gd. Experiments in vivo showed a decrease in tumor T1 over 24 hours in treated animals injected with C2A-GST-Gd, compared with controls. These data suggest that Gd3+-based contrast agents may detect apoptosis in vitro and in vivo.