The investigation of new Mn(II)-based MRI/Molecular Imaging probes responsive to the enzyme tyrosinase for potential diagnostic applications is herein described. The expression of the enzyme tyrosinase, an oxidoreductase, is up-regulated in melanoma cancer cells. Three novel ligands (L1, L2 and L3) were designed as modified acyclic polyaminocarboxylate chelates by introducing an l-tyrosine residue in place of an aminoacetate unit. The corresponding Mn(II) complexes were fully characterised by 1H NMR relaxometric techniques in aqueous media. The responsive activity towards the expression of tyrosinase was then assessed by monitoring the 1H 1/T1 relaxivity changes during incubation experiments in buffered solutions containing tyrosinase at different concentrations and in B16F10 melanoma cell homogenate. New insight on the mechanism of action of these systems was gained by measuring the magnetic field dependence of the relaxivity and ESR spectra of the incubated solutions. The systems developed showed responsive activity to tyrosinase with a relaxation enhancement spanning from 50% (MnL1) to 350% (MnL3) which augurs well for the development of diagnostic probes to detect melanoma cancer.
Responsive Mn(II) complexes for potential applications in diagnostic Magnetic Resonance Imaging
TEI, LORENZO;
2011-01-01
Abstract
The investigation of new Mn(II)-based MRI/Molecular Imaging probes responsive to the enzyme tyrosinase for potential diagnostic applications is herein described. The expression of the enzyme tyrosinase, an oxidoreductase, is up-regulated in melanoma cancer cells. Three novel ligands (L1, L2 and L3) were designed as modified acyclic polyaminocarboxylate chelates by introducing an l-tyrosine residue in place of an aminoacetate unit. The corresponding Mn(II) complexes were fully characterised by 1H NMR relaxometric techniques in aqueous media. The responsive activity towards the expression of tyrosinase was then assessed by monitoring the 1H 1/T1 relaxivity changes during incubation experiments in buffered solutions containing tyrosinase at different concentrations and in B16F10 melanoma cell homogenate. New insight on the mechanism of action of these systems was gained by measuring the magnetic field dependence of the relaxivity and ESR spectra of the incubated solutions. The systems developed showed responsive activity to tyrosinase with a relaxation enhancement spanning from 50% (MnL1) to 350% (MnL3) which augurs well for the development of diagnostic probes to detect melanoma cancer.
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