Methods: (111)In-DOTA-GlyGlu-CycMSH was prepared DNA Damage inhibitor and purified by reverse-phase high-performance liquid chromatography (RP-HPLC). The internalization and efflux of (111)In-DOTA-GlyGlu-CycMSH were examined in B16/F10 melanoma cells. The biodistribution of (111)In-DOTA-GlyGlu-CycMSH was determined in B16/F10 pulmonary metastatic melanoma-bearing and normal C57 mice. Pulmonary metastatic melanoma imaging was performed by small-animal single-photon emission
computed tomography (SPECT)/CT (Nano-SPECT/CT) using (111)In-DOTA-GlyGlu-CycMSH as an imaging probe and compared with 2-[(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG) positron emission tomography (PET) imaging.
Results: (111)In-DOTA-GlyGlu-CyCMSH was readily prepared with greater than 95% radiolabeling yield. (111)In-DOTA-GlyGlu-CycMSH displayed rapid internalization and extended efflux in B16/F10 cells. (111)In-DOTA-GlyGlu-CycMSH exhibited significantly (P<.05) higher uptakes (2.00 +/- 0.74%ID/g at 2 h post-injection and 1.83 +/- 0.12%ID/g at 4 h post-injection) in metastatic melanoma-bearing lung than that in normal lung (0.08 +/- 0.08%ID/g and 0.05 +/- 0.05%ID/g at 2 and 4 h post-injection, respectively). The activity accumulation in normal organs was low (<0.5%ID/g) except for the kidneys 2 and 4 h post-injection.
B16/F10 pulmonary melanoma metastases were clearly visualized C59 wnt ic50 with (111)In-DOTA-GlyGlu-CycMSH 2 h post-injection rather than with [(18)F]FDG 1 h post-injection.
Conclusions: (111)In-DOTA-GlyGlu-CycMSH exhibited favorable metastatic melanoma-targeting
and -imaging properties, highlighting its potential as an effective imaging probe for metastatic melanoma detection. (C) 2009 most Elsevier Inc. All rights reserved.”
“In the presence of gratuitous inducers, the lac operon of Escherichia coli exhibits bistability. Most models in the literature assume that the inducer enters the cell via the carrier (permease), and exits by a diffusion-like process. The diffusive influx and carrier efflux are neglected. However, analysis of the data shows that in non-induced cells, the diffusive influx is comparable to the carrier influx, and in induced cells, the carrier efflux is comparable to the diffusive efflux. Since bistability entails the coexistence of steady states corresponding to both non-induced and induced cells, neither one of these fluxes can be ignored. We present a model accounting for both fluxes, and show that: (1) The thresholds (i.e., the extracellular inducer levels at which transcription turns on or off) are profoundly affected by both fluxes. The diffusive influx reduces the on threshold, and eliminates irreversible bistability, a phenomenon that is inconsistent with data.