Tumor cell uptake of 99mTc-labeled 1-thio-ß-D-glucose and 5-thio-D-glucose in comparison with 2-deoxy-2-[18F]fluoro-D-glucose in vitro: kinetics, dependencies, blockage and cell compartment of accumulation.

PURPOSE: This study was conducted to investigate the capacity of (99m)Tc-labeled 1-thio-ß-D-glucose ((99m)Tc-1-TG) and 5-thio-D-glucose ((99m)Tc-5-TG) to act as a marker for glucose metabolism in tumor cells in vitro. PROCEDURES: We investigated the cellular uptake of (99m)Tc-1-TG, (99m)Tc-5-TG, and 2-deoxy-2-[(18)F]fluoro-D-glucose((18)F-FDG) in a human colorectal carcinoma and human lung adenocarcinoma cell line (HCT-116, A549) at different time points and varying glucose/insulin concentrations and under transporter blockage by cytochalasin-B and phloretin. Cell compartment analysis was performed. RESULTS: A significant uptake and time dependency thereof, a significant uptake dependency on glucose and insulin and a significant uptake inhibition by cytochalasin-B for (99m)Tc-1-TG and (99m)Tc-5-TG, was shown. Albeit substantial, the uptake was less pronounced in (99m)Tc-1-TG and (99m)Tc-5-TG compared with (18)F-FDG. (99m)Tc-1-TG and (99m)Tc-5-TG showed a higher accumulation in the cell membranes compared with (18)F-FDG. CONCLUSION: Tc-1-TG and (99m)Tc-5-TG showed an uptake in vitro with glucose analog characteristics but with membranous accumulation. Tumor imaging should be investigated in an animal model.

Pro-inflammatory effector Th cells transmigrate through anti-inflammatory environments into the murine fetus.

The presence of maternal DNA or even maternal cells within the offspring (microchimerism) has been reported for many fetal tissues, including the liver, heart, and spleen. Microchimerism is believed to be involved in the pathogenesis of autoimmune diseases; however, the cellular origin of this phenomenon remains unknown. Here, we determined whether differentiated T lymphocytes could transmigrate through the immunosuppressive environment of the placenta to reach the fetus. In vitro-differentiated effector/memory Th1 and Th17 cells from OVA323₋339-specific TCR(tg) T cells of OT-II mice were adoptively transferred (i.v.) into the tail veins of pregnant Ly5.1 mice at d15 and d19 of gestation. Mice were then sacrificed 40 h after adoptive cell transfer. Using radioactive labeling of T cells with sodium chromate [Cr5¹] prior to adoptive transfer, we observed that homing of pro-inflammatory Th cells was equally efficient in both pregnant and non-pregnant mice. Transmigration of Th1- and Th17-like cells through the highly immunosuppressive environment of the placenta into the fetus was significantly enhanced in experimental mice compared to control mice (P < 0.0001). In addition, a substantial amount of effector Th cells accumulated in the placenta. Finally, we found that treatment with Pertussis Toxin resulted in a 3-fold increase in the transmigration of effector Th17 cells into the fetus (P < 0.0001). When pro-inflammatory Th1-or Th17-like cells were injected into syngeneic mothers, almost all of the fetuses analyzed exhibited radioactivity, suggesting that transmigration of effector T cells occurs frequently. Our results suggest the possibility of novel roles for these maternal effector cells in the pathogenesis or reduction of disease.