Cytosolic/microsomal redox pathway: a reductive retention mechanism of a PET-oncology tracer, Cu-pyruvaldehyde-bis(N 4-methylthiosemicarbazone) (Cu-PTSM)

Abstract

Cu-PTSM and its derivatives are considered to be used as a marker for microsome/cytosol redox ability in PET oncology, although the physiological role of the redox enzyme system in tumor cells has not been clarified. The change in electron (NADH) flow in tumor cells might be a mechanism supporting aerobic glycolysis in tumor cells.

PET imaging of cardiac hypoxia: Opportunities and challenges

“…In brain, 70-80% of Cu-PTSM and Cu-ATSM was reduced by mitochondria, while in a variety of cancer cell types, mitochondrial retention is reported to represent approximately 10% of the total [82,[100][101][102]. Thus far, reduction of these complexes has only been investigated in individual subcellular fractions [100,[103][104][105], rather than intact tissues which have been exposed to copper complexes and then fractionated. Errors in accounting for relative differences in volumes and concentrations of each fraction potentially skew the measured contribution of each fraction to total cellular bioreduction, but some tissue-specific differences have been identified nonetheless.…”

Radiolabeling Rhesus Monkey CD34+Hematopoietic and Mesenchymal Stem Cells with64Cu-Pyruvaldehyde-Bis(N4-Methylthiosemicarbazone) for MicroPET Imaging

“…In normal, noncancerous cells, Cu(II)-PTSM has been shown to be reduced specifically in the mitochondria. 29,30 The copper molecule subsequently enters the pathway of copper metabolism remaining in the cytosol bound to metallothioneins and other proteins. 27,31 Although copper is very important physiologically, it can be toxic when available in excess.…”

Opportunities and Challenges for Metal Chemistry in Molecular Imaging

“…Use of PET to quantitatively map blood flow requires a tracer that is trapped in cells efficiently and indiscriminately so that the uptake of tracer in a tissue is dependent only on its delivery via blood and not on other tissue or cell characteristics. Bioreduction provides this mechanism for CuPTSM (93), which is believed to be as follows: the complex is a small, planar, lipophilic molecule that is able to readily diffuse through cell membranes to reach the intracellular milieu, where it encounters cellular reducing agents (the identity of which is unknown or the subject of debate) and is reduced to a Cu(I) species. This species rapidly dissociates, releasing the Cu(I) to become bound to intracellular macromolecules and thus trapped within the cell.…”