Dual-modality imaging with 99mTc and fluorescent indocyanine green using surface-modified silica nanoparticles for biopsy of the sentinel lymph node: an animal study

Abstract

BackgroundWe propose a new approach to facilitate sentinel node biopsy examination by multimodality imaging in which radioactive and near-infrared (NIR) fluorescent nanoparticles depict deeply situated sentinel nodes and fluorescent nodes with anatomical resolution in the surgical field. For this purpose, we developed polyamidoamine (PAMAM)-coated silica nanoparticles loaded with technetium-99m (99mTc) and indocyanine green (ICG).MethodsWe conducted animal studies to test the feasibility and utility of this dual-modality imaging probe. The mean diameter of the PAMAM-coated silica nanoparticles was 30 to 50 nm, as evaluated from the images of transmission electron microscopy and scanning electron microscopy. The combined labeling with 99mTc and ICG was verified by thin-layer chromatography before each experiment. A volume of 0.1 ml of the nanoparticle solution (7.4 MBq, except for one rat that was injected with 3.7 MBq, and 1 μg of an ICG derivative [ICG-sulfo-OSu]) was injected submucosally into the tongue of six male Wistar rats.ResultsScintigraphic images showed increased accumulation of 99mTc in the neck of four of the six rats. Nineteen lymph nodes were identified in the dissected neck of the six rats, and a contact radiographic study showed three nodes with a marked increase in uptake and three nodes with a weak uptake. NIR fluorescence imaging provided real-time clear fluorescent images of the lymph nodes in the neck with anatomical resolution. Six lymph nodes showed weak (+) to strong (+++) fluorescence, whereas other lymph nodes showed no fluorescence. Nodes showing increased radioactivity coincided with the fluorescent nodes. The radioactivity of 15 excised lymph nodes from the four rats was assayed using a gamma well counter. Comparisons of the levels of radioactivity revealed a large difference between the high-fluorescence-intensity group (four lymph nodes; mean, 0.109% ± 0.067%) and the low- or no-fluorescence-intensity group (11 lymph nodes; mean, 0.001% ± 0.000%, p < 0.05). Transmission electron microscopy revealed that small black granules were localized to and dispersed within the cytoplasm of macrophages in the lymph nodes.ConclusionAlthough further studies are needed to determine the appropriate dose of the dual-imaging nanoparticle probe for effective sensitivity and safety, the results of this animal study revealed a novel method for improved node detection by a dual-modality approach for sentinel lymph node biopsy.

Radiolabeled Dendrimers for Nuclear Medicine Applications

“…Hence, noninvasive imaging of SNL using radiolabeled dendrimer-based NPs has attracted a great deal of attention in the field of cancer diagnosis and therapy. Tsuchimochi et al developed G3 PAMAM dendrimer-coated silica NPs loaded with 99m Tc and indocyanine green (ICG) for SPECT/NIR imaging of SNL [ 74 ]. The formed dendrimers were injected into the tongue of rats, and then these NPs were able to clearly depict sentinel lymph nodes in real time via dual-modal SPECT/NIR imaging.…”

Radio-nanomaterials for biomedical applications: state of the art

“…Silica-based hybrid nanostructures are another category of PET/fluorescence contrast agents. For example, PAMAM-coated silica nanoparticles loaded with 99m Tc and indocyanine green (ICG) were used for SLN mapping (85). NIR fluorescence imaging provided realtime clear fluorescent images of the lymph nodes with anatomical resolution.…”

Dual-Labeled Near-Infrared/99mTc Imaging Probes Using PAMAM-Coated Silica Nanoparticles for the Imaging of HER2-Expressing Cancer Cells

“…Nanoscale particle technologies have progressed in recent years [ 2 , 4 , 5 ]. We previously reported the use of functionalized silica nanoparticle probes-polyamidoamine (PAMAM) dendrimer coated silica nanoparticles (PCSNs) loaded with technetium-99m ( 99m Tc) and indocyanine green (ICG)—to image sentinel lymph nodes in an experimental animal model [ 6 ]. Multifunctional nanoparticles including multimodal imaging probes have the potential to create revolutionary changes in medicine [ 1 , 7 ].…”