MRI reporter genes

Abstract

Noninvasive molecular imaging of dynamic processes has benefited tremendously from the use of reporter genes. These genes encode for proteins that emit light, bind radiolabeled probes, or, as covered in this review, modulate MRI contrast. Reporter genes play a pivotal role in monitoring cell trafficking, gene replacement therapy, protein-protein interactions, neuronal plasticity, and embryonic development. Several strategies exist for generating MRI contrast: using enzyme-catalyzed chemical modification of metal-based contrast agents or (phosphorus) metabolites, iron-binding and iron-storage proteins to accumulate iron as a contrast agent, and artificial proteins for imaging based on chemical exchange saturation transfer. MRI reporter genes have the advantage that the specific signal can be coregistered with soft-tissue anatomy and functional tissue information and have, therefore, become an active and growing area of scientific interest.

Figure 1. Principles of the CEST contrast mechanism

A frequency-selective saturation pulse is applied to label amide protons (A, green) or guanidyl protons (C, red) of a polypeptide contrast agent. The labeled protons exchange with water protons, which leads to a reduction in MR signal intensity (ΔSI) in a frequency-selective manner (B and D). CEST maps of MRI phantoms were acquired with frequency-selective saturation pulses; E) at ±3.7 ppm which enhances PLL, f) at ±1.8 ppm, which enhances PLA, and G) at ± 0.8 ppm which enhances PLT. The merged composition image of maps (E-G) is shown in (H). [Modified from (24) and (23)].

Figure 2. MRI detection of endothelial over-expression of H-ferritin in transgenic mice

Expression of ferritin was regulated by the VE cadherin promoter in double transgenic mice, but not in single transgenic siblings. Elevated R2 was observed in the liver and heart of E13.5 embryos studied in utero (A), and in the brain of adult mice (B). Adapted from Ref (18).