Iron(III)? <i>t</i> CDTA derivatives as MRI contrast agents: Increased T ₁ relaxivities at higher magnetic field strength and pH sensing

Purpose Low molecular weight iron(III) complex-based contrast agents (IBCA) including trans-cyclohexane diamine tetraacetic acid [Fe(tCDTA)]? could serve as alternatives to gadolinium-based in MRI. In search for IBCA with enhanced properties, we synthesized derivatives of and compared their effects. Methods Trans-cyclohexane (tCDTA) was chemically modified 2 steps: first the monoanhydride generated, then it coupled amines second step. After purification, chelators were analyzed by high-performance liquid chromatography, mass spectrometry, NMR spectrometry. The complexed iron(III), relaxivities complexes measured at 0.94, 1.5, 3, 7 Tesla. Kinetic stabilities spectrophotometrically redox properties cyclic voltammetry. Results Using ethylenediamine (en) trans-1,4-diaminocyclohexane, generated monomers dimers tCDTA: en-tCDTA, en-tCDTA-dimer, trans-1,4-diaminocyclohexane-tCDTA, trans-1,4-diaminocyclohexane-tCDTA-dimer. these had similarly high [Fe(tCDTA)]?. trans-1,4-diaminocyclohexane higher T1 than that increased increasing magnetic field strengths highest 6.8 L·mmol?1·s?1 per molecule dimer. Remarkably, relaxivity [Fe(en-tCDTA)]+ a threefold increase from neutral pH toward pH6. Conclusion Four similar stability comparison synthesized. trans-1,4-diaminocyclohexane-tCDTA trans-1,4-diaminocyclohexane-tCDTA-dimer same range 3 complex is sensor weakly acidic levels, which are typical various cancer types.