Disease relevance of Cu-ATSM

• Cu-Diacetyl-bis(N(4)-methylthiosemicarbazone) (Cu-ATSM) is a recently developed PET imaging agent for tumor hypoxia [1].
• CONCLUSION: Cu-ATSM exhibits selectivity for hypoxic tumor tissue both in vivo and in vitro and may provide a successful diagnostic modality for the detection of tumor ischemia [2].
• For the four mice with low activity Cu-ATSM scans performed before hyperthermia, the tumours to be heated demonstrated self-normalized uptake consistent with the unheated control tumours and which departed significantly (p < or = 0.02) from their post-hyperthermia scans by 5 min [3].
• These results indicated the possibility of Cu-ATSM being an effective SOD-like drug for the treatment of superoxide-mediated damage, such as ischemia-reperfusion injury [4].
• With Cu-ATSM and reversed phase HPLC analysis, the reductive metabolism of Cu-ATSM in subcellular fractions obtained from Ehrlich ascites tumor cells was examined [5].

High impact information on Cu-ATSM

• Using canine models of hypoxic myocardium, we report our findings on *Cu-ATSM PET (*Cu is defined as either (60)Cu, (61)Cu, or (64)Cu) for the delineation of ischemic and hypoxic myocardium [6].
• RESULTS: In this study, Cu-ATSM was reduced by hypoxic but not by normal mitochondria [7].
• We further demonstrated the feasibility of Cu-ATSM-guided IMRT by showing an example in which radiation dose to the hGTV could be escalated without compromising normal tissue (parotid glands and spinal cord) sparing [8].
• 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 [9].
• However, the additional alkylation present in Cu-ATSE modifies the hypoxia selectivity and in vivo properties when compared with Cu-ATSM [10].

Biological context of Cu-ATSM

• Lipid peroxidation levels in the Cu-ATSM treated group were lower than those in the non-treated group [4].

Anatomical context of Cu-ATSM

• In the present study 64Cu(t1/2 = 12.8 h) labeled Cu-ATSM was used in combination with 11C (t1/2 = 20.3 min) labeled acetate as a regional perfusion marker to visualize hypoxic rat heart tissue in an acute left anterior descending (LAD) coronary artery occluded rat model using an ex vivo tissue slice imaging technique [11].
• The reduction process in the microsome/cytosol was heat-sensitive and enhanced by adding exogenous NAD(P)H, an indication of enzymatic reduction of Cu-ATSM in tumor cells [5].

Gene context of Cu-ATSM

• Cu-ATSM, an intracellular-accessible superoxide dismutase (SOD)-like copper complex: evaluation in an ischemia-reperfusion injury model [4].
• Among the known bioreductive enzymes, NADH-cytochrome b5 reductase and NADPH-cytochrome P450 reductase in microsome played a major role in the reductive retention of Cu-ATSM in tumors [5].

Analytical, diagnostic and therapeutic context of Cu-ATSM

• Using PET and electronic autoradiography, Cu-ATSM uptake was measured in tumor tissue under various pO2 levels [12].
• We have also compared the uptake of Cu-ATSM and Cu-PTSM in vivo and ex vivo in a murine animal model bearing the EMT6 tumor [2].
• A recently developed positron emission tomography (PET) imaging-based hypoxia measurement technique which employs a Cu(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) (Cu-ATSM) tracer is of great interest [8].
• PET imaging with FMISO and Cu-ATSM is ready for coordinated multicenter trials, however, that should move aggressively forward to resolve the debate over the importance of hypoxia in limiting response to cancer therapy [13].

References