In vivo evaluation of (64)Cu-labeled magnetic nanoparticles as a dual-modality PET/MR imaging agent

Abstract

A novel nanoparticle-based dual-modality positron emission tomograph/magnetic resonance imaging (PET/MRI) contrast agent was developed. The probe consisted of a superparamagnetic iron oxide (SPIO) core coated with PEGylated phospholipids. The chelator 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to PEG termini to allow labeling with positron-emitting (64)Cu. Radiolabeling with (64)Cu at high yield and high purity was readily achieved. The (64)Cu-SPIO probes produced strong MR and PET signals and were stable in mouse serum for 24 h at 37 degrees C. Biodistribution and in vivo PET/CT imaging studies of the probes showed a circulation half-life of 143 min and high initial blood retention with moderate liver uptake, making them an attractive contrast agent for disease studies.

Figure 1

(A) Schematic representation dual-modality ⁶⁴Cu-mSPIO. (B) Transmission electron micrograph of uniform monocrystalline superparamagnetic iron oxide nanoparticles. (C) Dynamic light scattering showing highly monodisperse populations of mSPIO before (closed bars) and after (open bars) encapsulation in PEGylated lipid micelle. (D) In vitro stability of ⁶⁴Cu-mSPIO over the course of 24 hr incubation in 37 °C mouse serum.

Figure 2

Biodistribution data of dual-PET/MRI ⁶⁴Cu-mSPIO (10 mg Fe/kg body weight) in BALB/c mice. Groups of mice (n = 4) were sacrificed at 10 min, 1 hr, 4 hr, and 24 hr and select organs were measured for activity. Data are expressed as percent injected dose per gram tissue (%ID/g, top) and percent injected dose per organ (%ID/organ, bottom) ± one standard deviation.

Figure 3

Coregistered microPET/microCT of BALB/c mice administered 100 μCi of ⁶⁴Cu-mSPIOs (10 mg Fe/kg body weight, 100 μL injection volume). Whole body sagittal (A–E) and coronal (B–F) PET images are decay corrected and scaled by min/max frame: (A, B) 1 hr; (C, D) 4 hr; and (E, F) 24 hr post-injection.

Figure 4

PET and MR imaging of ⁶⁴Cu-mSPIO phantoms. (A) T²-weighted image of 25 μg Fe/mL (top) and 10 μg Fe/mL (bottom) of ⁶⁴Cu-labeled magnetic nanoparticles (scale bar corresponds to high and low iron concentration). (B) Decay-corrected microPET image of 25 μg Fe/mL (top) and 10 μg Fe/mL (bottom) of ⁶⁴Cu-labeled magnetic nanoparticles (scale bar corresponds to high and low copper-64 concentration).