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Abstract #1900

A Single Amino Acid Gd-Complex as a Modular Tool for High Relaxivity MR Contrast Agent Development.

Eszter Boros1, Miloslav Polasek1, Zhaoda Zhang1, Peter Caravan2

1Department of Radiology, Massachusetts General Hospital, Harvard Medical School, The Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States; 2Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, United States

We investigated applications of the alanine analogue of Gd(DOTA), Gd(DOTAla). Fmoc protected DOTAla suitable for solid phase peptide synthesis was synthesized and integrated into polypeptide structures containing 1-3 Gd(DOTAla) complexes (GdL1, GdL2, GdL3).GdL3 is superior to commercial contrast agents gadoteridol and gadofosveset /HSA (human serum albumin) at high fields. The modularity of design, the ease of solid phase synthesis, high kinetic inertness (t1/2 = 614h) for Gd3, and optimal water exchange rate renders the Gd(DOTAla) scaffold a suitable platform for the development of high field T1 agents based on Gd.

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Keywords

absence acid address agent agents alanine albumin allow allowed amino analogue applications approved audience basic benefits best biomedical caravan chemistry clinically commercial complex complexes compounds containing contrast control correlation decreasing dependence derivative design determined development dynamics ease excess exchange facile fast field fields frequencies full function gadolinium general greater hospital human increasing indicated inertness influence inner integrated integration intermediate inversion investigated investigation kinetic kinetics ligand maintaining manganese measured media medical modular modularity molecular molecule much noise optimal outperforming peptide peter platform plotted potent presence protected radiology ranging rapid recovery renders residency rotational scaffold school science serum slow solid sphere stability strength strengths structures studies suitable superior synthesis synthesized target temperature thermodynamic tool transverse tumbling variety water