Synthesis and characterization of a porphyrazine-Gd(III) MRI contrast agent and in vivo imaging of a breast cancer xenograft model

Evan R. Trivedi, Zhidong Ma, Emily A. Waters, Keith W. Macrenaris, Rohit Subramanian, Anthony G.M. Barrett, Thomas J. Meade, Brian M. Hoffman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Porphyrazines (Pz), or tetraazaporphyrins, are being studied for their potential use in detection and treatment of cancer. Here, an amphiphilic Cu-Pz-Gd(III) conjugate has been prepared via azide-alkyne Huisgen cycloaddition or 'click' chemistry between an azide functionalized Pz and alkyne functionalized DOTA-Gd(III) analog for use as an MRI contrast agent. This agent, Cu-Pz-Gd(III), is synthesized in good yield and exhibits solution-phase ionic relaxivity (r1=11.5 mm-1 s-1) that is approximately four times higher than that of a clinically used monomeric Gd(III) contrast agent, DOTA-Gd(III). Breast tumor cells (MDA-MB-231) associate with Cu-Pz-Gd(III) in vitro, where significant contrast enhancement (9.336±0.335 contrast-to-noise ratio) is observed in phantom cell pellet MR images. This novel contrast agent was administered in vivo to an orthotopic breast tumor model in athymic nude mice and MR images were collected. The average T1 of tumor regions in mice treated with 50 mg kg-1 Cu-Pz-Gd(III) decreased relative to saline-treated controls. Furthermore, the decrease in T1 was persistent relative to mice treated with the monomeric Gd(III) contrast agent. An ex vivo biodistribution study confirmed that Cu-Pz-Gd(III) accumulates in the tumors and is rapidly cleared, primarily through the kidneys. Differential accumulation and T1 enhancement by Cu-Pz-Gd(III) in the tumor's core relative to the periphery offer preliminary evidence that this agent would find application in the imaging of necrotic tissue.

Original languageEnglish (US)
Pages (from-to)313-322
Number of pages10
JournalContrast Media and Molecular Imaging
Issue number4
StatePublished - 2014


  • Click chemistry
  • MRI contrast agent
  • Porphyrazine
  • Tumor imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


Dive into the research topics of 'Synthesis and characterization of a porphyrazine-Gd(III) MRI contrast agent and in vivo imaging of a breast cancer xenograft model'. Together they form a unique fingerprint.

Cite this