One of the most commonly used Cu(II)-bis(thio-semicarbazone) is Cu(II)-pyruvaldehyde-bis(N4-methylthiosemicarbazone) ([Cu]PTSM), (Fig. 11.5). [62/64Cu]PTSM is a highly lipophilic complex, and is used as a blood flow tracer. Following administration of [62/64Cu]PTSM, tissue uptake is rapid, and the tracer is trapped in most major tissues such as the brain [77-80], heart [77, 78, 81], and tumors [82-85]. Tissue retention of [62/64Cu]PTSM and other frzs(thiosemicar-bazone) derivatives is believed to result when the lipophilic complex diffuses across the cell membrane. The Cu(II) is then reduced to Cu(I), at which time the copper complex decomposes. Cu(I) is trapped by binding to intracellular macromolecules . Unlike [62/64Cu]PTSM, studies involving [60/62/64Cu(II)]diacetyl-fo's([N4]methylthiosemicarbazone) ([60/62/64Cu]ATSM) (Fig. 11.5) have shown that [60/62/64Cu]ATSM has selective uptake in hypoxic tissue [6, 87, 88]. Hypoxia is a condition in which the oxygen demands exceed the oxygen available. Hypoxic tissue can be found in my-ocardial infarction, brain injury, and tumors. The selectivity of hypoxic imaging agents is a balance between its redox potential and cell uptake. The cell uptake is important because hypoxic tissue has poor blood supply, and therefore the ability to deliver the tracer to the tissue is reduced. The difference in uptake of [62/64Cu]PTSM and [60/62/64Cu]ATSM is believed to result from the additional methyl group that results in a lower redox potential for [60/62/64Cu]ATSM. Research is on-going to develop new mixed frzs(thiosemicar-bazone) ligands in an attempt to develop superior hypoxic imaging agents [89-92].
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