Open AccessConcentration‐independent MRI of pH with a dendrimer‐based pH‐responsive nanoprobe
Author(s) -
Bhuiyan Mohammed P. I.,
Aryal Madhava P.,
Janic Branislava,
Karki Kishor,
Varma Nadimpalli R. S.,
Ewing James R.,
Arbab Ali S.,
Ali Meser M.
Publication year - 2015
Publication title -
contrast media & molecular imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.714
H-Index - 50
eISSN - 1555-4317
pISSN - 1555-4309
DOI - 10.1002/cmmi.1651
Subject(s) - nanoprobe , chemistry , dendrimer , relaxometry , gadolinium , relaxation (psychology) , nuclear magnetic resonance , magnetic resonance imaging , nanotechnology , materials science , nanoparticle , biochemistry , radiology , medicine , physics , organic chemistry , spin echo
The measurement of extracellular pH (pH e ) has significant clinical value for pathological diagnoses and for monitoring the effects of pH‐altering therapies. One of the major problems of measuring pH e 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 ( r 1 ) increased from 7.91 to 9.65 mM −1 s −1 (on a per Gd 3+ basis) on changing pH from 8.84 to 6.35. At 7 T, r 1 relaxivity showed pH response, albeit at lower mean values; transverse relaxivity ( r 2 ) 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 R 2 / R 1 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.