Intrinsically germanium-69-labeled iron oxide nanoparticles: synthesis and in-vivo dual-modality PET/MR imaging

Abstract

Intrinsically germanium-69-labeled super-paramagnetic iron oxide nanoparticles are synthesized via a newly developed, fast and highly specific chelator-free approach. The biodistribution pattern and the feasibility of (69) Ge-SPION@PEG for in vivo dual-modality positron emission tomography/magnetic resonance (PET/MR) imaging and lymph-node mapping are investigated, which represents the first example of the successful utilization of a (69) Ge-based agent for PET/MR imaging.

Keywords: chelator-free radiolabeling; germanium-69; iron oxide nanoparticles; multimodality imaging; positron emission tomography/magnetic resonance (PET/MR) imaging.

Figure 1

(a) A schematic illustration of chelator-free synthesis of ⁶⁹Ge-metal oxides. (b) TEM image of SPION. Inset shows a digital photo of SPION in cyclohexane solution. (c) TEM image of SPION@PAA. Inset shows a digital photo of SPION@PAA in aqueous solution. (d) Time-dependent ⁶⁹Ge labeling yield of SPION and other nanoparticles. (e) Autoradiograph of TLC plates of ⁶⁹Ge-SPION (top) and free ⁶⁹Ge (bottom). (f) Serum stability study of PEGylated (black line) and non-PEGylated ⁶⁹Ge-SPION (red line) in whole mouse serum at 37 °C.

Figure 2

(a) Serial in vivo PET images of ⁶⁹Ge-SPION@PEG (top) and free ⁶⁹Ge (bottom) after i.v. injection into mice. (b) In vivo T₂*-weighted MR images of mice before and after i.v. of Ge-SPION@PEG (in PBS). Transaxial images are presented to show the liver uptake of Ge-SPION@PEG, as well as lack of accumulation or contrast enhancement in the kidneys.

Figure 3

(a) In vivo lymph node imaging with PET after subcutaneous injection of ⁶⁹Ge-SPION@PEG into the left footpad of the mouse. Lymph nodes and paws were indicated by green and red arrows, respectively. (b) Quantification of the ⁶⁹Ge-SPION@PEG uptake by the lymph node and the mouse paw (n = 3). (c) In vivo lymph node mapping with MRI before and after injection of Ge-SPION@PEG into the left footpad of the mouse. Obvious darkening of the lymph node could be seen (dashed green circle), whereas no contrast enhancement was observed for the contralateral lymph node (dashed red circle).