Myelin-targeted, texaphyrin-based multimodal imaging agent for magnetic resonance and optical imaging.
Reliable methods of imaging myelin are essential to investigate the causes of demyelination and to study drugs that promote remyelination. Myelin-specific compounds can be developed into imaging probes to detect myelin with various imaging techniques. The development of multimodal myelin-specific imaging probes enables the use of orthogonal imaging techniques to accurately visualize myelin content and validate experimental results. Here, we describe the synthesis and application of multimodal myelin-specific imaging agents for light microscopy and magnetic resonance imaging. The imaging agents were synthesized by incorporating the structural features of luxol fast blue MBS, a myelin-specific histological stain, into texaphyrins coordinated to GdIII. These new complexes demonstrated absorption of visible light, emission of near-IR light, and relaxivity values greater than clinically approved contrast agents for magnetic resonance imaging. These properties enable the use of optical imaging and magnetic resonance imaging for visualization of myelin. We performed section- and en block-staining of ex vivo mouse brains to investigate the specificity for myelin of the new compounds. Images obtained from light microscopy and magnetic resonance imaging demonstrate that our complexes are retained in white matter structures and enable detection of myelin. Copyright © 2016 John Wiley & Sons, Ltd.
Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, 48202, MI, USA.|Department of Chemistry, University of Colombo, Colombo 03, Sri Lanka.
Sashiprabha M
SM
Vithanarachchi
Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, 48202, MI, USA.
Casey D
CD
Foley
Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, 48202, MI, USA.
Sarah
S
Trimpin
Department of Neurology, Henry Ford Hospital, Detroit, MI, 48202, USA.
James R
JR
Ewing
Department of Neurology, Henry Ford Hospital, Detroit, MI, 48202, USA.
Meser M
MM
Ali
Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, 48202, MI, USA.
Matthew J
MJ
Allen
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008853:Microscopy; D064847:Multimodal Imaging / Q000379:methods*; D009186:Myelin Sheath; D061848:Optical Imaging; D011166:Porphyrins; D066127:White Matter / Q000000981:diagnostic imaging*
D003287:Contrast Media; D011166:Porphyrins; C442892:texaphyrin; D005682:Gadolinium
MRI; contrast agents; gadolinium; multimodal probes; myelin; optical imaging; paramagnetic agents; texaphyrin