A self-calibrating PARACEST MRI contrast agent that detects esterase enzyme activity
Version of Record online: 30 NOV 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Contrast Media & Molecular Imaging
Volume 6, Issue 4, pages 219–228, July/August 2011
How to Cite
Li, Y., Sheth, V. R., Liu, G. and Pagel, M. D. (2011), A self-calibrating PARACEST MRI contrast agent that detects esterase enzyme activity. Contrast Media Mol Imaging, 6: 219–228. doi: 10.1002/cmmi.421
- Issue online: 17 AUG 2011
- Version of Record online: 30 NOV 2010
- Manuscript Accepted: 18 AUG 2010
- Manuscript Revised: 3 JUL 2010
- Manuscript Received: 16 APR 2010
- contrast agent;
- enzyme activity
The CEST effect of many PARACEST MRI contrast agents changes in response to a molecular biomarker. However, other molecular biomarkers or environmental factors can influence CEST, so that a change in CEST is not conclusive proof for detecting the biomarker. To overcome this problem, a second control CEST effect may be included in the same PARACEST agent, which is responsive to all factors that alter the first CEST effect except for the biomarker to be measured. To investigate this approach, a PARACEST MRI contrast agent was developed with one CEST effect that is responsive to esterase enzyme activity and a second control CEST effect. The ratio of the two CEST effects was independent of concentration and T1 relaxation, so that this agent was self-calibrating with respect to these factors. This ratiometric method was dependent on temperature and was influenced by MR coalescence as the chemical exchange rates approached the chemical shifts of the exchangable protons as temperature was increased. The two CEST effects also showed evidence of having different pH dependencies, so that this agent was not self-calibrating with respect to pH. Therefore, a self-calibrating PARACEST MRI contrast agent can more accurately detect a molecular biomarker such as esterase enzyme activity, as long as temperature and pH are within an acceptable physiological range and remain constant. Copyright © 2010 John Wiley & Sons, Ltd.