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
Publication statusPublished - Nov 1 2015

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Keywords

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

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Bhuiyan, M. P. I., Aryal, M. P., Janic, B., Karki, K., Varma, N. R. S., Ewing, J. R., ... 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