Concentration‐independent MRI of pH with a dendrimer‐based pH‐responsive nanoprobe |
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Authors: | Mohammed P I Bhuiyan Madhava P Aryal Branislava Janic Kishor Karki Nadimpalli R S Varma James R Ewing Ali S Arbab Meser M Ali |
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Institution: | 1. Henry Ford Hospital, Detroit, MI, USA;2. Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA |
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Abstract: | The measurement of extracellular pH (pHe) has significant clinical value for pathological diagnoses and for monitoring the effects of pH‐altering therapies. One of the major problems of measuring pHe with a relaxation‐based MRI contrast agent is that the longitudinal relaxivity depends on both pH and the concentration of the agent, requiring the use of a second pH‐unresponsive agent to measure the concentration. Here we tested the feasibility of measuring pH with a relaxation‐based dendritic MRI contrast agent in a concentration‐independent manner at clinically relevant field strengths. The transverse and longitudinal relaxation times in solutions of the contrast agent (GdDOTA‐4AmP)44‐G5, a G5–PAMAM dendrimer‐based MRI contrast agent in water, were measured at 3 T and 7 T magnetic field strengths as a function of pH. At 3 T, longitudinal relaxivity (r1) increased from 7.91 to 9.65 mM?1 s?1 (on a per Gd3+ basis) on changing pH from 8.84 to 6.35. At 7 T, r1 relaxivity showed pH response, albeit at lower mean values; transverse relaxivity (r2) remained independent of pH and magnetic field strengths. The longitudinal relaxivity of (GdDOTA‐4AmP)44‐G5 exhibited a strong and reversible pH dependence. The ratio of relaxation rates R2/R1 also showed a linear relationship in a pH‐responsive manner, and this pH response was independent of the absolute concentration of (GdDOTA‐4AmP)44‐G5 agent. Importantly, the nanoprobe (GdDOTA‐4AmP)44‐G5 shows pH response in the range commonly found in the microenvironment of solid tumors. Copyright © 2015 John Wiley & Sons, Ltd. |
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Keywords: | responsive agent noninvasive pH measurement magnetic resonance imaging dendritic agent |
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