In Vivo Imaging with a Cell-Permeable Porphyrin-Based MRI Contrast Agent

Abstract

SUMMARY Magnetic resonance imaging (MRI) with molecular probes offers the potential to monitor physiological parameters with comparatively high spatial and temporal resolution in living subjects. For detection of intracellular analytes, construction of cell-permeable imaging agents remains a challenge. Here we show that a porphyrin-based MRI molecular imaging agent, Mn-(DPA-C2)2-TPPS3, effectively penetrates cells and persistently stains living brain tissue in intracranially injected rats. Chromogenicity of the probe permitted direct visualization of its distribution by histology, in addition to MRI. Distribution was concentrated in cell bodies after hippocampal infusion. Mn-(DPA-C2)2-TPPS3 was designed to sense zinc ions, and contrast enhancement was more pronounced in the hippocampus, a zinc-rich brain region, than in the caudate nucleus, which contains relatively little labile Zn2+. Membrane permeability, optical activity, and high relaxivity of porphyrin-based contrast agents offer exceptional functionality for in vivo imaging.

Porphysome nanoparticles: Tailoring treatments with nature’s pigments

“…Metalation can also impart interesting properties independent of the porphyrins' photonic properties. Mn 3+ and Cu 2+ are capable of affecting the magnetic relaxation times of the surrounding water molecules in a strong magnetic field, such as that used in magnetic resonance imaging (MRI) [72][73][74][75][76][77]. This allows paramagnetic porphyrins to act as MRI contrast agents.…”

Zinc as an Imaging Biomarker of Prostate Cancer

“…The most notable examples have been probes that detect zinc and insulin co-secretion from pancreatic β-cells in response to an increase in plasma glucose, [36] a cell-permeable porphyrin-based MR probe that highlights zinc-rich tissues such as the hippocampus in mouse brain, [37] and probes that detect zinc secretion from the prostate. [38] …”

A cell-permeable gadolinium contrast agent for magnetic resonance imaging of copper in a Menkes disease model

“…Previous biological, MR-based metal ion sensing has largely focused on Zn physiology, including elegant studies by Sherry and co-workers on the use of a Gd-based zinc sensor for the in vivo detection of extracellular zinc released by pancreatic beta cells 31 and Lippard, Jasanoff, and colleagues on the application of a cell-permeable Mn-based contrast agent to sense zinc levels in vivo . 30,40 Encouraged by the large dynamic range of CG2, we sought to exploit its properties in the design of an MR contrast agent for the imaging of Cu + in living systems. The +1 oxidation state of copper dominates in intracellular spaces; we expected that CG2, like other typical Gd 3+ -containing MR contrast agents such as Gd-DTPA and Gd-DOTA, would be largely confined to the extracellular space due to a poor ability to cross cellular membranes.…”