Manganese-porphyrin-enhanced MRI for the detection of cancer cells: A quantitative in vitro investigation with multiple clinical subtypes of breast cancer

PLoS One. 2018 May 24;13(5):e0196998. doi: 10.1371/journal.pone.0196998. eCollection 2018.

Abstract

Magnetic resonance imaging (MRI) contrast agents (CAs) are chemical compounds that can enhance image contrast on T1- or T2- weighted MR image. We have previously demonstrated the potential of MnCl2, a manganese-based CA, in cellular imaging of breast cancer using T1-weighted MRI. In this work, we examined the potential of another class of manganese-based CAs, manganese porphyrins (MnPs), for sensitive cellular detection of multiple clinical subtypes of breast cancer using quantitative MRI. Using a clinical 3.0-T MRI scanner, the relaxivities of two MnPs, MnTPPS4 and MnTPPS3NH2, and conventional Gd-DTPA (control) were measured in ultrapure water and their T1 contrast enhancement patterns were characterized in multiple clinical subtypes of breast cancer. The toxicity of the three CAs was evaluated in vitro. Compared to Gd-DTPA, both MnTPPS3NH2 and MnTPPS4 enabled a more sensitive multi-subtype detection of four breast cell lines at doses that posed no cytotoxic effects, with MnTPPS3NH2 producing the greatest positive enhancement. The superior T1 enhancement capabilities of MnPs over Gd-DTPA are statistically significant and are likely due to their greater cellular uptake and relaxivities. The results demonstrate that multiple clinical subtypes of breast cancer can be imaged on a 3.0-T MRI scanner using MnPs as T1 cellular CAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Contrast Media / chemistry
  • Contrast Media / pharmacokinetics*
  • Contrast Media / pharmacology
  • Female
  • Gadolinium DTPA / chemistry
  • Gadolinium DTPA / pharmacokinetics*
  • Gadolinium DTPA / pharmacology
  • Humans
  • MCF-7 Cells
  • Magnetic Resonance Imaging / instrumentation
  • Magnetic Resonance Imaging / methods*
  • Porphyrins / chemistry
  • Porphyrins / pharmacokinetics*
  • Porphyrins / pharmacology

Substances

  • Contrast Media
  • Porphyrins
  • tetraphenylporphine sulfonate
  • Gadolinium DTPA

Grants and funding

Funded by Heart & Stroke Foundation of Canada (#000223 to HLMC) http://www.heartandstroke.ca/. Natural Sciences and Engineering Research Council of Canada (#355795 to HLMC) http://www.nserc-crsng.gc.ca/index_eng.asp. SickKids Foundation (to HLMC). NSERC Alexander Graham Bell Canada Graduate Scholarships - Doctoral (to MA). Ontario Graduate Scholarship (to MA). National Science Foundation of China (#51303155 to YL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.