The imaging of sentinel lymph nodes (SLN) has been researched for its role in assessing cancer progression and postsurgical lymphedema. Indocyanine green (ICG) is a near-infrared (NIR) optical dye that has been approved by the Food and Drug Administration. It is known that liposome-encapsulated ICG (LP-ICG) has improved stability and fluorescence signal compared with ICG. We designed mannosylated liposome-encapsulated ICG (M-LP-ICG) as an optical contrast agent for SLN. M-LP-ICG has a higher UV absorbance spectrum and fluorescence intensity than LP-ICG. The stability of M-LP-ICG measured in 50% fetal bovine serum solution by a dialysis method was better than that of LP-ICG. M-LP-ICG demonstrated a high uptake in RAW 264.7 macrophage cell because the density of mannose is high. There were differences between M-LP-ICG and glucosylated liposome-encapsulated ICG (G-LP-ICG), which are geometrical isomers. The result of an inhibition study of M-LP-ICG showed a statistically significant decrease in uptake in RAW 264.7 cells after either co-treatment or pre-treatment with D-(+)-mannose as an inhibitor. Results from an in vitro experiment demonstrated that M-LP-ICG was specifically taken up by macrophage cells through the mannose receptor on its surface. The time-series images acquired from a normal mouse model after subcutaneous injection showed that the signal from M-LP-ICG in SLN and other organs appeared early and disappeared quickly in comparison with signals from LP-ICG. Not only the sentinel but also the draining lymph nodes were observed partly in M-LP-ICG. M-LP-ICG appears to increase the specificity of uptake and retention in macrophages, making it a good candidate contrast agent for an optic imaging system for SLN and the lymphatic system.

The most widely used method for increasing uptake on macrophage is specific targeting for mannose receptor (MR) presented on macrophages. Efficiency of the uptake for MR is influenced by the space length and flexibility of mannose ligand in liposome (LP). We prepared mannosylated liposomes (M-EGn-LP-ICG) encapsulated indocyanine green (ICG) with mannose ligand of various ethylene glycol units (EG), LP-ICG, and mannosylated liposome (M-LP-ICG) incorporated with p-aminophenyl-α-d-mannopyranoside. We studied the effect of space length of the mannose ligand in vitro and in vivo with prepared liposomes. A space length of two ethylene glycol units at least was needed for uptake by macrophages and the uptake was increased as the space length increased up to EG4. We measured near-infrared (NIR) fluorescence intensity by ICG and the fluorescence value of cell-associated N-(4-nitrobenzo-2-oxa-1,3-diazole) (NBD) in liposome after cellular uptake. M-EG4-LP-ICG showed lower NIR fluorescence intensity but higher NBD fluorescence value than M-LP-ICG. The result of pre-treatment with d(+)-mannose as an inhibitor showed significant decreasing in uptake of mannosylated LP-ICG but no difference in LP-ICG. These were explained that mannosylated LP-ICG was taken up by macrophages through the MR and M-EG4-LP-ICG showed more specific uptake than M-LP-ICG. We obtained images as time passed in the NIR range after intravenous administration using a Balb/c mouse with inflammatory model. The results showed high uptake in liver at early time and rapid degradation of mannosylated LP-ICG. M-EG4-LP-ICG was more selectively taken up by macrophages than M-LP-ICG.

PurposeThe glutathione-S-transferase (GST)P1, GSTM1, and GSTT1 genotypes have been associated with an increased risk of prostate, bladder, and lung cancers. The aim of this study was to investigate the association between the GSTP1, GSTM1, and GSTT1 genotypes and the risk of prostate cancer in Korean men.Materials and MethodsThe study group consisted of 166 patients with histologically confirmed prostate cancer. The control group consisted of 327 healthy, cancer-free individuals. The diagnosis of prostate cancer was made by transrectal ultrasound-guided biopsy. Patients with prostatic adenocarcinoma were divided into organ-confined (≤pT2) and non-organ-confined (≥pT3) subgroups. The histological grades were subdivided according to the Gleason score. The GSTP1, GSTM1, and GSTT1 genotypes were determined by using polymerase chain reaction-based methods. The relationship among GSTP1, GSTM1, and GSTT1 polymorphisms and prostate cancer in a case-control study was investigated.ResultsThe frequency of the GSTM1 null genotype in the prostate cancer group (54.2%) was higher than in the control group (odds ratio=1.53, 95% confidence interval=1.20-1.96). The comparison of the GSTP1, GSTM1, and GSTT1 genotypes and cancer prognostic factors, such as staging and grading, showed no statistical significance.ConclusionsAn increased risk for prostate cancer may be associated with the GSTM1 null genotype in Korean men, but no association was found with the GSTT1 or GSTP1 genotypes.

Hepatocellular carcinoma (HCC) is one of the most serious health problems worldwide. Many researchers have investigated HCC at the level of genes, ribonucleic acid, proteins, cells, and animals. The resultant development of animal models and monitoring methods has improved the effectiveness of guidelines provided to researchers working with preclinical HCC models. HCC in animal models and clinical patients is monitored by various current imaging modalities such as ultrasound (US) imaging, computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), positron emission tomography (PET) and bioluminescence imaging (BLI). These techniques are currently used for both preclinical and clinical assessment, and provide valuable diagnostic information. In this article, we have mainly reviewed the established animal models and the assessment of orthotopic HCC using imaging modalities. Additionally, we have introduced a method of orthotopic HCC rat model developed in our laboratory. We have furthermore evaluated the occurrence of tumor mass using molecular imaging techniques.