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Fluorescent single-stranded DNA-based assay for detecting unchelated Gadolinium(III) ions in aqueous solution

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Abstract

The main concern pertaining to the safety of Gadolinium(III)-based contrast agents (GBCAs) is the toxicity caused by the unchelated ion, which may be inadvertently present in the solution due most commonly to excess unreacted starting material or dissociation of the complexes. Detecting the aqueous free ion during the synthesis and preparation of GBCA solutions is therefore instrumental in ensuring the safety of the agents. This paper reports the development of a sensitive fluorogenic sensor for aqueous unchelated Gadolinium(III) (Gd(III)). Our design utilizes single-stranded oligodeoxynucleotides with a specific sequence of 44 bases as the targeting moiety. The fluorescence-based assay may be run at ambient pH with very small amounts of samples in 384-well plates. The sensor is able to detect nanomolar concentration of Gd(III), and is relatively unresponsive toward a range of biologically relevant ions and the chelated Gd(III). Although some cross-reactivity with other trivalent lanthanide ions, such as Europium(III) and Terbium(III), is observed, these are not commonly found in biological systems and contrast agents. This convenient and rapid method may be useful in ascertaining a high purity of GBCA solutions.

Fluorescent aptamer-based assay for detecting unchelated Ln(III) ions in aqueous solution

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Notes

  1. We find no less than four recent examples of different research groups working on the development of novel MRI contrast agents, in which the xylenol orange assay was used to determine the purity of the synthesized agents. This list is by no means comprehensive and updated, as we did not look for all publications on Gd-based MRI CAs. For examples of articles published by these groups, please see references [16–19].

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Acknowledgements

We would like to gratefully acknowledge Dr. Milan N Stojanovic from Columbia University, New York, NY 10032 for valuable and inspiring scientific advice and discussion, and Dr. David Saloner and Dr. Bonnie Joe from the University of California San Francisco, Department of Radiology and Biomedical Imaging for the kind and generous donation of all the clinical contrast agents used. This work is supported by funding from the National Institute of Health (R21EB013347) to MN Stojanovic, California State University East Bay (CSUEB), and CSUEB Faculty Support Grant-Mentoring Student Researcher. O.E. was supported by the CSUEB Center for Student Research (CSR) Fellowship.

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  1. Department of Chemistry and Biochemistry, California State University East Bay, 25800 Carlos Bee Boulevard, Hayward, CA, 94542, USA

    Osafanmwen Edogun, Nghia Huu Nguyen & Marlin Halim

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  1. Osafanmwen Edogun
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  2. Nghia Huu Nguyen
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Correspondence to Marlin Halim.

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Edogun, O., Nguyen, N.H. & Halim, M. Fluorescent single-stranded DNA-based assay for detecting unchelated Gadolinium(III) ions in aqueous solution. Anal Bioanal Chem 408, 4121–4131 (2016). https://doi.org/10.1007/s00216-016-9503-2

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