In Vivo Imaging Probe for Visualizing and Measuring Autotaxin Activity
- Activated ATX-Red fluoresces in the near-infrared, the optimal spectral window for in vivo fluorescence imaging
- Near-IR fluorescence can be imaged up to 15 cm deep in living tissue (Ntziachristos and Weissleder, Opt Lett. 2001)
- ATX-Red AR-2 is an in vivo imaging probe for visualizing and measuring Autotaxin (ATX) activity. It is an analog of the autotaxin substrate lysophosphatidylcholine (LPC) and contains a near-infrared fluor (Licor IRDye® 800CW) and quencher (Licor IRDye® QC-1). When autotaxin cleaves ATX-Red AR-2, fluorescence increases. This activation mechanism is specific to autotaxin in vitro and in vivo.
- Autotaxin which has lysophospholipase D (lysoPLD) activity, cleaves choline from lysophosphatidylcholine forming lysophosphatidic acid (LPA), a potent mitogen that as been implicated in the pathophysiology of ovarian cancer. LysoPLD/ATX has been demonstrated to increase cell motility, neovascularization, proliferation and aggressiveness of tumors, and is upregulated in numerous cancer lineages (non-small cell lung, glioma, mammary carcinoma, renal cell carcinoma, hepatocellular carcinoma). In addition, dysregulation of the ATX/LPA pathway is central to the pathophysiology of idiopathic pulmonary fibrosis, rheumatoid arthritis, and other inflammatory diseases. Modulation of ATX activity through small-molecules is a currently underexplored target, but one with high potential for novel cancer and anti-inflammatory therapeutics.
A mouse bearing an MDA-MB-231 orthotopic tumor was injected with ATX-Red AR-2 by tail vein injection and imaged at 800 nm. Fluorescence is observed in the tumor where ATX activity is increased.
ATX-Red is a smart probe for imaging autotaxin activity in vivo.
- Ntziachristos and Weissleder, Optics Letters, Vol. 26, Issue 12, pp. 893-895 (2001) (Link)