Laboratory of Physiology of Cognitive Processes
2008
  • Title:Novel Calcium Sensitive MRI Contrast Agent: A Potential Agent for in vivo testing
  • Authors:K. Dhingra; M. E. Maier; M. Beyerlein; G. Angelovski; N. K. Logothetis
  • Title of Journal:World Molecular Imaging Congress 2008
  • Year:2008
  • DOI:
Abstract
Ca2+ plays an important dual role as a carrier of electrical current and as a second messenger in the brain. Its effects are much more diverse than of other second messengers such as cAMP (3',5'-cyclic adenosine monophosphate) and DAG (Diacylglycerol) as its actions are mediated by large array of proteins including protein kinases. Optical imaging with the help of fluorescent dyes has revealed the important role played by Ca2+; however it is limited by depth penetration and photobleaching side product. Magnetic Resonance Imaging (MRI), owing to its noninvasive characteristics together with its high spatial and temporal resolution doesn’t possess such limitations. In order to exploit these characteristics of MRI, Li. et al. (JACS comm. 1999) have proposed a smart contrast agent based on the high affinity chelator BAPTA, showing sensitivity to Ca2+ concentration in the range of 0.1 to 10 ?M with an apparent dissociation constant of 0.96 ?M. Contrast agents with such a strong affinity Ca2+ chelator are likely to be saturated once the Ca2+ concentration exceeds 1?M. We report here the synthesis of a Ca2+ sensitive smart contrast agent based on a low affinity chelator APTRA (o-aminophenol-N,N,O-triacetate). The agent showed 100% relaxivity enhancement in presence of Ca2+. Besides its excellent sensitivity, the agent was found Ca2+ selective in the presence of Mg2+ and Zn2+. Its relaxivity response in physiological media such as artificial cerebro-spinal fluid (ACSF) and artifici