Sang Bong Lee

Combined Positron Emission Tomography and Cerenkov Luminescence Imaging of Sentinel Lymph Nodes Using PEGylated Radionuclide-Embedded Gold Nanoparticles.

New imaging probes with high sensitivity and stability are urgently needed to accurately detect sentinel lymph nodes (SLNs) for successful cancer diagnosis. Herein, the use of highly sensitive and stable PEGylated radionuclide-embedded gold nanoparticles (PEG-RIe-AuNPs) is reported for the detection of SLNs by combined positron emission tomography and Cerenkov luminescence imaging (PET/CLI). PEG-RIe-AuNPs show high sensitivity and stability both in vitro and in vivo, and are not toxic to normal ovarian and immune cells. In vivo PET/CLI imaging clearly reveals SLNs as early as 1 h post PEG-RIe-AuNP-injection, with peak signals achieved at 6 h postinjection, which is consistent with the biodistribution results. Taken together, the data provide strong evidence that PEG-RIe-AuNPs are promising as potential lymphatic tracers in biomedical imaging for pre and intraoperative surgical guidance.

Visualization of Macrophage Recruitment to Inflammation Lesions using Highly Sensitive and Stable Radionuclide-Embedded Gold Nanoparticles as a Nuclear Bio-Imaging Platform

Reliable and sensitive imaging tools are required to track macrophage migration and provide a better understating of their biological roles in various diseases. Here, we demonstrate the possibility of radioactive iodide-embedded gold nanoparticles (RIe-AuNPs) as a cell tracker for nuclear medicine imaging. To demonstrate this utility, we monitored macrophage migration to carrageenan-induced sites of acute inflammation in living subjects and visualized the effects of anti-inflammatory agents on this process. Macrophage labeling with RIe-AuNPs did not alter their biological functions such as cell proliferation, phenotype marker expression, or phagocytic activity. In vivo imaging with positron-emission tomography revealed the migration of labeled macrophages to carrageenan-induced inflammation lesions 3 h after transfer, with highest recruitment at 6 h and a slight decline of radioactive signal at 24 h; these findings were highly consistent with the data of a bio-distribution study. Treatment with dexamethasone (an anti-inflammation drug) or GSK5182 (an ERRγ inverse agonist) hindered macrophage recruitment to the inflamed sites. Our findings suggest that a cell tracking strategy utilizing RIe-AuNPs will likely be highly useful in research related to macrophage-related disease and cell-based therapies.

Engineering of Radioiodine-Labeled Gold Core–Shell Nanoparticles As Efficient Nuclear Medicine Imaging Agents for Trafficking of Dendritic Cells

The development of highly sensitive, stable, and biocompatible imaging agents allowing visualization of dendritic cell (DC) migration is one of the essential factors for effective DC-based immunotherapy. Here, we used a novel and efficient synthesis approach to develop radioiodine-124-labeled tannic acid gold core-shell nanoparticles (124I-TA-Au@AuNPs) for DC labeling and in vivo tracking of their migration using positron emission tomography (PET). 124I-TA-Au@AuNPs were produced within 40 min in high yield via straightforward tannic acid-mediated radiolabeling chemistry and incorporation of Au shell, which resulted in high radio-sensitivity and excellent chemical stability of nanoparticles in DCs and living mice. 124I-TA-Au@AuNPs demonstrated good DC labeling efficiency and did not affect cell biological functions, including proliferation and phenotype marker expression. Importantly, 124I-TA-Au@AuNPs in an extremely low amount (0.1 mg/kg) were successfully applied to track the migration of DCs to lymphoid organs (draining lymph nodes) in mice.

Antigen‐Free Radionuclide‐Embedded Gold Nanoparticles for Dendritic Cell Maturation, Tracking, and Strong Antitumor Immunity

Dendritic cell (DC)-based cancer immunotherapy requires efficient maturation of DCs and sensitive monitoring of DCs localized in the lymph nodes that activate T cells. This paper reports a robust and simple surface chemistry for highly sensitive and stable radionuclide-embedded gold nanoparticles (Poly-Y-RIe-AuNPs) prepared with oligotyrosine-modified AuNPs with additional Au shell formation as a promising positron emission tomography/computed tomography imaging agent. The multiple oligotyrosine binding sites modified on AuNPs provide excellent stability for conjugated radioisotopes by forming an Au shell. They can be heavily conjugated with radioisotope iodine, which enables sensitive tracking of DCs in the lymphatic system. More importantly, it is found that the maturation of DCs is possible solely with Poly-Y-RIe-AuNPs without any additional stimulus for DC maturation. DCs matured by Poly-Y-RIe-AuNPs induce antitumor immunity to cervical cancer comparable to that produced from DCs pulsated with tumor lysates. These results demonstrate that the peptide-based surface chemistry of Poly-Y-RIe-AuNPs is a simple and straightforward method to produce a highly sensitive and stable nuclear medicine imaging agent that also improves the efficiency of current antitumor immunotherapies.

Multimodality Imaging of Bone Marrow–Derived Dendritic Cell Migration and Antitumor Immunity

Here, we sought to monitor bone marrow–derived dendritic cell (BMDC) migration and antitumor effects using a multimodal reporter imaging strategy in living mice. BMDCs were transduced with retroviral vector harboring human sodium iodide symporter (hNIS, nuclear imaging reporter), firefly luc2 (optical imaging reporter), and thy1.1 (surrogate marker of NIS and luc2) genes (BMDC/NF cells). No significant differences in biological functions, including cell proliferation, antigen uptake, phenotype expression, and migration ability, were observed between BMDC and BMDC/NF cells. Combined bioluminescence imaging and I-124 positron emission tomography/computed tomography clearly revealed the migration of BMDC/NF cells to draining popliteal lymph nodes at day 7 postinjection. Interestingly, marked tumor protection was observed in mice immunized with TC-1 lysate-pulsed BMDC/NF cells. Our findings suggested that multimodal reporter gene imaging of NIS and luciferase could provide insights into the biological behaviors of dendritic cells in living organisms and could be a useful tool for the optimization of DC-based immunotherapy protocols.

Impact of Ultrasmall Platinum Nanoparticle Coating on Different Morphologies of Gold Nanostructures for Multiple One-Pot Photocatalytic Environment Protection Reactions

Here, we report the preparation of various morphologies of core-satellite hybrid plasmonic nanomaterials of gold and platinum, viz., the coating of platinum nanoparticles on gold nanostars (Pt@AuNSs), nanospheres (Pt@AuNPs), and nanorods (Pt@AuNRs) for visible-NIR-sunlight illuminated highly efficient photoconversion of CO2 to HCOOH and visible light mediated degradation of various organic dyes (methylene blue, methyl orange, and methyl red) in a single step at room temperature. In comparison, Pt@AuNSs shows higher conversion efficiency for CO2 photoconversion to HCOOH with 1.52% of quantum yield and 2.58% of chemical yield in visible-light illumination. There was a 200-fold increase in the conversion efficiency after PtNP coating to AuNSs. On the other hand, Pt@AuNPs (quantum yield = 1.44%) and Pt@AuNRs (quantum yield = 0.64%) also show the significant conversion rate in visible and NIR light, respectively. All the hybrid nanoparticles were found to be stable, whereas PtNPs increase the stability of AuNSs incredibly, during the photoconversion reaction and reused for five CO2 reduction reaction cycles without losing photocatalytic activity. Moreover, Pt@AuNSs also showed higher photocatalytic activity for organic pollutant degradation and degraded methylene blue, methyl red, and methyl orange in 45, 75, and 80 min with 0.104 min-1, 0.055 min-1, and 0.044 min-1 reaction rate, respectively. The results highlighted the crucial role of PtNPs as a highly efficient cocatalyst as well as the impact of increases in surface area with the change in morphology of gold nanostructures on CO2 photoconversion and organic dye degradation.

Tracking dendritic cell migration into lymph nodes by using a novel PET probe 18F-tetrafluoroborate for sodium/iodide symporter

BackgroundRecently, 18F-tetrafluoroborate (TFB) was used as a substrate for the human sodium/iodide symporter (hNIS) reporter gene. This study evaluated the feasibility of performing molecular-genetic imaging by using the new radiotracer (18F-TFB) for the hNIS gene, to track dendritic cell (DC) migration in live mice. A murine dendritic cell line (DC2.4) co-expressing the hNIS and effluc genes (DC/NF) was established. To confirm the functional cellular expression of both effluc and NIS in the inoculated DC/NF cells by bio-medical imaging, combined bioluminescence imaging (BLI) and 18F-TFB positron emission tomography/computed tomography (PET/CT) imaging was performed after intramuscular injection with parental DCs and DC/NF cells. For DC-tracking, parental DCs or DC/NF cells were injected in the left or right mouse footpad, respectively, and 18F-TFB PET/CT and BLI were performed to monitor these cells in live mice.ResultsIn vivo PET/CT and BLI showed a clear signal in DC/NF injection sites but not in parental DC injection sites. The signal intensity in DC/NF cells was correlated with time. In vivo 18F-TFB PET/CT imaging showed higher radiotracer activity in the draining popliteal lymph nodes (DPLNs) in DC/NF injection sites than those in DC injection sites on day 2. BLI also showed DC/NF cell migration to the DPLNs on day 2 after the injection.ConclusionsMigration of DCs to the lymph nodes was successfully monitored using 18F-TFB PET/CT imaging of the NIS gene and optical imaging of the effluc gene in live mice. These data support the feasibility of using 18F-TFB as a substrate for hNIS reporter gene imaging to track the migration of DCs to the lymph nodes in live animals. The use of 18F-TFB may facilitate enhanced PET imaging of the hNIS reporter gene in small animals and humans in future studies.