Chelator-Free Conjugation of 99mTc and Gd3+ to PEGylated Nanographene Oxide for Dual-Modality SPECT/MR Imaging of Lymph Nodes.

PEGylated ultrasmall nanographene oxide (usNGO-PEG) has exhibited a great potential in nanotheranostics due to its newly discovered physicochemical properties derived from the rich functional groups and bonds. Herein, we developed a general, simple, and kitlike preparation approach for 99mTc- and Gd-anchored NGO-PEG using a chelator-free strategy. In this strategy, [99mTcI(CO)3(OH2)3]+ (abbreviated to 99mTcI) and GdCl3 were mixed with usNGO-PEG to yield 99mTc- and Gd-usNGO-PEG via the synergistic coordination of N and O atoms from NGO and PEG with 99mTcI and Gd3+ without additional exogenous chelators. Under optimized conditions, the nanoprobes 99mTc- and Gd-usNGO-PEG were reliably prepared with high yields and good stability. Serial comparative experiments of the labeling yield, the measurements of -NH2 density and ζ-potentials, and various characterizations including energy-dispersive X-ray analysis spectroscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy demonstrated that both usNGO and PEG synergistically provide the electron-donating atoms O and N to coordinate with 99mTcI and Gd to form stable nanocomplexes. Furthermore, both 99mTc- and Gd-usNGO-PEG exhibited excellent in vivo imaging of lymph nodes using single-photon emission computed tomography/computed tomography (SPECT/CT) and magnetic resonance (MR) imaging after local injection. Therefore, these results showed the successful establishment of 99mTc- and Gd-anchored usNGO-PEG using a chelator-free strategy and the potential of multimodality SPECT/CT and MR imaging of lymph nodes.