Cell line-dependent differences in uptake and retention of the hypoxia-selective nuclear imaging agent Cu-ATSM
| Autor: | Paul Burgman, C. Clifton Ling, John L. Humm, Joseph A. O'Donoghue, Michael J. Welch, Jason S. Lewis |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Thiosemicarbazones
Cancer Research Biology Incubation period Coordination Complexes Neoplasms Organometallic Compounds Tumor Cells Cultured Animals Humans Tissue Distribution Radiology Nuclear Medicine and imaging Radionuclide Imaging Incubation Tumor hypoxia Metabolism Oxygenation Anoxic waters Cell Hypoxia Rats Oxygen Copper Radioisotopes Biochemistry Cell culture Biophysics Molecular Medicine Female Copper Intracellular |
| Zdroj: | Nuclear Medicine and Biology. 32:623-630 |
| ISSN: | 0969-8051 |
| DOI: | 10.1016/j.nucmedbio.2005.05.003 |
| Popis: | Background Cu-diacetyl-bis( N 4 -methylthiosemicarbazone) [Cu-ATSM] is a potential marker for tumor hypoxia that has been under evaluation for clinical use. In this study, we examined the mechanisms underlying the uptake of 64 Cu in cells incubated with 64 Cu-ATSM. Methods The in vitro uptake of 64 Cu was determined as a function of oxygenation conditions and incubation time with 64 Cu-ATSM using four and two tumor cell lines of human origin and rodent origin, respectively. Additionally, the rate of 64 Cu efflux and Cu-ATSM metabolism was determined. Results 64 Cu accumulation is rapid during the first 0.5–1 h of incubation. It is highest in anoxic cells but is also significant in normoxic cells. After this initial period, the level of intracellular 64 Cu varies depending on the cell line and the oxygenation conditions and, in some circumstances, may decrease. During the first 0.5–1 h, the ratio of 64 Cu levels between anoxic and normoxic cells is ∼2:10 and that between hypoxic (0.5% O 2 ) and normoxic cells is ∼1:2.5, depending on the cell line. These ratios generally decrease at longer times. The 64 Cu-ATSM compound was found to be metabolized during incubation in a manner dependent on oxygenation conditions. Within 2 h under anoxic conditions, 64 Cu-ATSM could no longer be detected, although 60–90% of the amount of 64 Cu added as 64 Cu-ATSM was present in the medium. Non-ATSM 64 Cu was taken up by the cells, albeit at a much slower rate. Efflux rates of 64 Cu were found to be cell line dependent and appeared to be inversely correlated with the final 64 Cu uptake levels under anoxic conditions. Conclusion The uptake and retention of 64 Cu and their relation to oxygenation conditions were found to be cell line dependent. Given the complexities in the oxygen dependence and cell line-dependent kinetics of uptake and retention of Cu following exposure to Cu-ATSM, the clinical utility of this compound may be disease site specific. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect