Methylated tetra-amide derivatives of paramagnetic complexes for magnetic resonance biosensing with both BIRDS and CEST.

Autor: Zakaria ABM; Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.; Magnetic Resonance Research Center, Yale University, New Haven, Connecticut, USA., Huang Y; Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.; Magnetic Resonance Research Center, Yale University, New Haven, Connecticut, USA., Coman D; Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.; Magnetic Resonance Research Center, Yale University, New Haven, Connecticut, USA., Mishra SK; Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.; Magnetic Resonance Research Center, Yale University, New Haven, Connecticut, USA., Mihailovic JM; Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.; Magnetic Resonance Research Center, Yale University, New Haven, Connecticut, USA., Maritim S; Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.; Magnetic Resonance Research Center, Yale University, New Haven, Connecticut, USA., Rojas-Quijano FA; Macrocyclics, Dallas, Texas, USA., Jurek P; Macrocyclics, Dallas, Texas, USA., Kiefer GE; Macrocyclics, Dallas, Texas, USA., Hyder F; Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.; Magnetic Resonance Research Center, Yale University, New Haven, Connecticut, USA.; Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.
Jazyk: angličtina
Zdroj: NMR in biomedicine [NMR Biomed] 2022 Jun; Vol. 35 (6), pp. e4687. Date of Electronic Publication: 2022 Jan 27.
DOI: 10.1002/nbm.4687
Abstrakt: Paramagnetic agents that utilize two mechanisms to provide physiological information by magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) are described. MRI with chemical exchange saturation transfer (CEST) takes advantage of the agent's exchangeable protons (e.g., -OH or -NH x , where 2 ≥ x ≥ 1) to create pH contrast. The agent's incorporation of non-exchangeable protons (e.g., -CH y , where 3 ≥ y ≥ 1) makes it possible to map tissue temperature and/or pH using an MRSI method called biosensor imaging of redundant deviation in shifts (BIRDS). Hybrid probes based upon 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate chelate (DOTA 4- ) and its methylated analog (1,4,7,10-tetraazacyclododecane-α, α', α″, α‴-tetramethyl-1,4,7,10-tetraacetate, DOTMA 4- ) were synthesized, and modified to create new tetra-amide chelates. Addition of several methyl groups per pendent arm of the symmetrical chelates, positioned proximally and distally to thulium ions (Tm 3+ ), gave rise to favorable BIRDS properties (i.e., high signal-to-noise ratio (SNR) from non-exchangeable methyl proton peaks) and CEST responsiveness (i.e., from amide exchangeable protons). Structures of the Tm 3+ probes elucidate the influence of methyl group placement on sensor performance. An eight-coordinate geometry with high symmetry was observed for the complexes: Tm-L1 was based on DOTA 4- , whereas Tm-L2 and Tm-L3 were based on DOTMA 4- , where the latter contained an additional carboxylate at the distal end of each arm. The distance of Tm 3+ from terminal methyl carbons is a key determinant for sustaining BIRDS temperature sensitivity without compromising CEST pH contrast; however, water solubility was influenced by introduction of hydrophobic methyl groups and hydrophilic carboxylate. Combined BIRDS and CEST detection of Tm-L2, which features two high-SNR methyl peaks and a strong amide CEST peak, should enable simultaneous temperature and pH measurements for high-resolution molecular imaging in vivo.
(© 2022 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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