Some thoughts on the mechanism of cellular trapping of Cu(II)-ATSM.

摘要: Cu(II)-ATSM continues to be investigated, both in the laboratory and clinic, as a tumor hypoxia imaging agent. However, meaningful interpretation of these images requires more complete understanding mechanism by which tracer is trapped within cell. simple molecule its biochemical interaction with cells similarly simple, mainly based upon redox chemistry. Here we suggest that trapping biphasic. The first phase reduction/oxidation cycle involving thiols molecular oxygen. This can followed proteins mitochondria leading permanent retention tracer. uptake complicated this second step because changes cell resulting from hypoxia, such an increase nicotinamide adenine dinucleotide (NADH) state differences cellular biochemistry proteomes. These may lead extent (64)Cu different types. For example, copper might increased lower pH due stability metal bis(thiosemicarbazones) under acidic conditions. Reaction rates reductants also vary pH, differs between organelles. reach full potential, characterization types required.