Mn-citrate and Mn-HIDA: intermediate-affinity chelates for manganese-enhanced MRI
Article first published online: 21 NOV 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Contrast Media & Molecular Imaging
Volume 8, Issue 2, pages 140–146, March/April 2013
How to Cite
Seo, Y., Satoh, K., Morita, H., Takamata, A., Watanabe, K., Ogino, T., Hasebe, T. and Murakami, M. (2013), Mn-citrate and Mn-HIDA: intermediate-affinity chelates for manganese-enhanced MRI. Contrast Media Mol Imaging, 8: 140–146. doi: 10.1002/cmmi.1510
- Issue published online: 21 NOV 2012
- Article first published online: 21 NOV 2012
- Manuscript Accepted: 13 SEP 2012
- Manuscript Revised: 11 SEP 2012
- Manuscript Received: 8 MAR 2012
- functional MRI;
In this study we investigated two manganese chelates in order to improve the image enhancement of manganese-enhanced MRI and decrease the toxicity of free manganese ions. Since both MnCl2 and a low-affinity chelate were associated with a slow continuous decrease of cardiac functions, we investigated intermediate-affinity chelates: manganese N-(2-hydroxyethyl)iminodiacetic acid (Mn-HIDA) and Mn-citrate. The T1 relaxivity values for Mn-citrate (4.4 m m−1 s−1) and Mn-HIDA (3.3 m m−1 s−1) in artificial cerebrospinal fluid (CSF) were almost constant in a concentration range from 0.5 to 5 m m at 37 °C and 4.7 T. In human plasma, the relaxivity values increased when the concentrations of these Mn chelates were decreased, suggesting the presence of free Mn2+ bound with serum albumin. Mn-HIDA and Mn-citrate demonstrated a tendency for better contractility when employed with an isolated perfused frog heart, compared with MnCl2. Only minimal changes were demonstrated after a venous infusion of 100 m m Mn-citrate or Mn-HIDA (8.3 µmol kg−1 min−1) in rats and a constant heart rate, arterial pressure and sympathetic nerve activity were maintained, even after breaking the blood–brain barrier (BBB). Mn-citrate and Mn-HIDA could not cross the intact BBB and appeared in the CSF, and then diffused into the brain parenchyma through the ependymal layer. The responses in the supraoptic nucleus induced by the hypertonic stimulation were detectable. Therefore, Mn-citrate and Mn-HIDA appear to be better choices for maintaining the vital conditions of experimental animals, and they may improve the reproducibility of manganese-enhanced MRI of the small nuclei in the hypothalamus and thalamus. Copyright © 2012 John Wiley & Sons, Ltd.