Measuring the age of a blood clot can be useful for the detection of acute thrombosis. To this end, Galen S. Loving and Peter Caravan, Harvard Medical School, Charlestown, USA, have developed an activatable magnetic resonance (MR) probe for the detection of fresh blood clots.
The probe responds to protein disulfide isomerase (PDI), which is a protein-folding chaperone that exists on the surface of activated platelets, and binds noncovalently to fibrin upon activation. The researchers modified a known probe bearing gadolinium(III) complexes by adding cystamine groups to the two cysteine side chains. In the presence of PDI, a disulfide bond is formed, and the probe cyclizes and binds to fibrin (see picture).
The binding also results in a 70 % increase in the relaxivity of the gadolinium(III) complexes. Thus, the probe can be used to differentiate between new and old clots, although the lack of PDI in old clots means that very small amounts of the probe are bound and thus accurate detection is difficult.
The researchers acknowledge that free thiols in blood could result in background activation and accumulation of the probe at old clots, however this process is slow relative to the rate of elimination of the probe from the body.
- Activation and Retention: A Magnetic Resonance Probe for the Detection of Acute Thrombosis,
Galen S. Loving, Peter Caravan,
Angew. Chem. Int. Ed. 2013.