pH-Sensitive cyanine dyes for optical imaging of acidic environments

MEDI 101

Scott A. Hilderbrand, Scott_Hilderbrand@hms.harvard.edu and Ralph Weissleder. Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, 149 13th St. Rm 5404, Charlestown, MA 02129
There is intense interest in the design of fluorogenic near infrared (NIR) probes for imaging applications. These environment responsive sensors, when coupled to nanoparticle scaffolds, benefit from increased in vivo retention times and enhanced signal via delivery of multiple fluorophores to the desired target. In this report development of nano-scale NIR fluorescence-based particles for pH imaging is reported. Abnormal tissue pH is commonly associated with pathophysiological disorders such as cancer, atherosclerosis, cysitic fibrosis and various renal conditions. Imaging probes for interrogation of these environments may ultimately allow for earlier disease diagnosis. For effective visualization of acidified tissues in vivo, careful design of a bright, water-soluble pH-sensitive fluorochrome is critical. To meet these requirements, new highly soluble pH-responsive cyanine dyes were developed in which the dye pKa can be tuned to match the acidic environment of interest. Ratiometric probes can be prepared by conjugation of the pH-sensitive reporters and pH-insensitive reference fluorophores to a suitable nano-scaffold. The functionality of these probes is demonstrated by visualization acidic intracellular compartments and by fluorescence reflectance imaging in mouse models.

 

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007