Target binding improves relaxivity in aptamer–gadolinium conjugates
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MRI contrast agents (CA) have been heavily used over the past several decades to enhance the diagnostic value of the obtained images. From a design perspective, two avenues to improve the efficacy of contrast agents are readily evident: optimization of magnetic properties of the CA, and optimization of the pharmacokinetics and distribution of the CA in the patient. Contrast agents consisting of DNA aptamer–gadolinium(III) conjugates provide a single system in which these factors can be addressed simultaneously. In this proof-of-concept study, the 15mer thrombin aptamer was conjugated to diethylenetriaminepentaacetic (DTPA) dianhydride to form a monoamide derivative of the linear open-chain chelate present in the commonly used contrast agent Magnevist®. The stability of the conjugated DNA aptamer–DTPA–Gd(III) chelate in a transmetallation study using Zn(II) was found to be similar to that reported for DTPA–Gd(III). Relaxivity enhancements of 35 ± 4 and 20 ± 1 % were observed in the presence of thrombin compared to a control protein at fields of 9.4 and 1.5 T, respectively. The inclusion of spacers between the aptamer and the DTPA to eliminate possible steric effects was also investigated but not found to improve the relaxation enhancement achieved in comparison to the unaltered aptamer conjugate.
KeywordsDNA aptamers Aptamer–gadolinium conjugates Magnetic resonance imaging DTPA Targeted contrast agents
MCD thanks the Natural Sciences and Engineering Council of Canada (NSERC), the Canadian Foundation for Innovation, The Ottawa Hospital/Ottawa Hospital Research Institute, the Ontario Research Fund, and the Ontario Ministry of Research and Innovation for supporting this work. EDB and MAB thank NSERC for graduate funding. EDB thanks Alaa Alsaafin and Uyen Ho for technical help. The authors acknowledge Keith Bourque (Carleton University) for assistance with the T 1 measurements at 9.4 T.
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