Synthesis of multimeric MR contrast agents for cellular imaging

Abstract

We have prepared a series of molecular multimeric MR contrast agents for cell labeling that are easy to synthesize, relatively low molecular weight, and biocompatible. The relaxivities of the agents range from 17 to 85 mM(-1) s(-1). Cellular uptake is concentration dependent and viability is excellent. MR images of cell pellets reveal a marked increase in observed signal intensity.

Figure 1

Synthetic scheme of multimeric MR contrast agents via click chemistry.

Figure 2

(A) T₁ weighted spin–echo MR phantom images of DOTA-Gd, 4, 5, and 6 in Millipore water at equal molar concentration of each contrast agent. Images were acquired at 4.7 T at 25 °C (T_R/T_E = 300/18.4 ms). Concentrations (from left to right): 62, 51, 37, 21, 7, 0 μM. (B) T₁ weighted spin–echo images of pelleted NIH-3T3 cells incubated with DOTA-Gd, 5, and 6 at approximately equal molar concentrations of Gd(III) (0, 7.60, 7.6, and 8.3 mM Gd(III), respectively). Images were acquired at 4.7 T at 25 °C (T_R/T_E = 500/12.5). Each sample diameter is 1 mm.