Lanthanoid complexes as enzyme-activated responsive MRI contrast agents
Final Report Abstract
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology for the visualization of soft tissues within the body. Commercial contrast agents like Gd-DOTA or Gd-DTPA enhance the image contrast but are non-specific; development of specific, targeted MRI contrast agents could however help identify and treat serious diseases like cancer. The goal of this research project to obtain such a specific, targeted MRI contrast agent was achieved by reacting a strained octyne-modified 3,2-HOPO-TAM chelate with an azide-modified cyclic RGD peptide in a strain-promoted "click reaction" to form chelate-peptide conjugate "SDK-191" (only one of two isomers shown). Complexation with GdCl3 afforded the desired Gd(III)-3,2-HOPO-TAM RGD peptide conjugate "SDK-194". RGD is a cyclic peptide comprised of the three amino acids arginine, glycine and tyrosine. It has a high and specific affinity for alpha v beta 3 -integrin, which is over-expressed in blood vessel forming cells in certain tumor types. The abundance of these integrins has been correlated to tumor grade, so their detection plays an important role in tumor diagnosis. MRI imaging of cells overexpressing the integrin receptor show a higher relaxivity (brighter image) for the integrin-targeted RGD-conjugate "SDK-194" (spot 4 and 5) than for the non-targeted reference complex (spot 2 and 3) and the cells alone (spot 1), suggesting a strong interaction of the targeted compound with the integrin receptors. Although commercialisation of this specific contrast agent is highly unlikely mostly due to the rather complicated synthesis, it would be interesting from an academic point-of-view to further probe the efficiency of "SDK-194" in an "in vivo" mouse model.
