Synthesis and physicochemical characterization of Gd-C4-thyroxin-DTPA, a potential MRI contrast agent. Evaluation of its affinity for human serum albumin by proton relaxometry, NMR diffusometry, and electrospray mass spectrometry.
Gd-C(4)-thyroxin-DTPA, a potential MRI contrast agent, was synthesized from Gd-DTPA and thyroxine, which interacts strongly with human serum albumin (HSA). It was characterized in water by its relaxometric properties and its stability versus zinc transmetalation. The affinity of the complex for HSA was studied by using three different methods: proton relaxometry, NMR diffusometry, and electrospray mass spectrometry. From the results, it appears that Gd-C(4)-thyroxin-DTPA exhibits a relatively high relaxivity (r(1) = 9.01 s(-1) mM(-1) at 1.5 T and 310 K), a good stability versus zinc transmetalation, and a strong interaction with HSA (K(a) approximately 10,000 M(-1) with two binding sites). The kinetics of the exchange between the bound and the free form of the complex was evaluated by the NMR diffusometry technique. Competition experiments have allowed the assignment of the chelate's binding site on HSA.
Henoumont
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Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, 19 avenue Maistriau, B-7000 Mons, Belgium.
Vander Elst
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Laurent
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Muller
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D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D004058:Diffusion; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013974:Thyroxine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D003287:Contrast Media; D009942:Organometallic Compounds; D012709:Serum Albumin; D013974:Thyroxine