Near infrared fluorescence-based bacteriophage particles for ratiometric pH imaging.
Fluorogenic imaging agents emitting in the near-infrared are becoming important research tools for disease investigation in vivo. Often pathophysiological states such as cancer and cystic fibrosis are associated with disruptions in acid/base homeostasis. The development of optical sensors for pH imaging would facilitate the investigation of these diseased conditions. In this report, the design and synthesis of a ratiometric near-infrared emitting probe for pH quantification is detailed. The pH-responsive probe is prepared by covalent attachment of pH-sensitive and pH-insensitive fluorophores to a bacteriophage particle scaffold. The pH-responsive cyanine dye, HCyC-646, used to construct the probe, has a fluorogenic pKa of 6.2, which is optimized for visualization of acidic pH often associated with tumor hypoxia and other diseased states. Incorporation of pH-insensitive reference dyes enables the ratiometric determination of pH independent of the probe concentration. With the pH-responsive construct, measurement of intracellular pH and accurate determination of pH through optically diffuse biological tissue is demonstrated.
Hilderbrand
Scott A
SA
Center for Molecular Imaging Research and Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, USA. Scott_Hilderbrand@hms.harvard.edu
Kelly
Kimberly A
KA
Niedre
Mark
M
Weissleder
Ralph
R
D001435:Bacteriophages / Q000378:metabolism*; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism; D019047:Phantoms, Imaging
D005456:Fluorescent Dyes