Concentration-independent MRI of pH with a dendrimer-based pH-responsive nanoprobe

Mohammed P.I. Bhuiyan, Madhava P. Aryal, Branislava Janic, Kishor Karki, Nadimpalli R.S. Varma, James R. Ewing, Ali S. Arbab, Meser M. Ali

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)481-486
Number of pages6
JournalContrast Media and Molecular Imaging
Volume10
Issue number6
DOIs
StatePublished - Nov 1 2015

Keywords

  • Dendritic agent
  • Magnetic resonance imaging
  • Noninvasive pH measurement
  • Responsive agent

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Bhuiyan, M. P. I., Aryal, M. P., Janic, B., Karki, K., Varma, N. R. S., Ewing, J. R., Arbab, A. S., & Ali, M. M. (2015). Concentration-independent MRI of pH with a dendrimer-based pH-responsive nanoprobe. Contrast Media and Molecular Imaging, 10(6), 481-486. https://doi.org/10.1002/cmmi.1651