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The retention mechanism of the novel imaging/radiotherapeutic agent, Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) in tumor cells was clarified in comparison with that in normal tissue in vitro. 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. As a reference, mouse brain was used. To determine the contribution of enzymes in the retention mechanisms, and specific inhibitor studies were performed. In subcellular fractions of tumor cells, Cu-ATSM was reduced mainly in the microsome/cytosol fraction rather than in the mitochondria. This finding was completely different from that found in normal brain cells. 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. 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. This enzymatic reduction was enhanced by the induction of hypoxia. Radiocopper labeled Cu-ATSM provides useful information for the detection of hypoxia as well as the microsomal bioreductive enzyme expression in tumor.

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To obtain a better understanding of the cortical representation of bimanual coordination, we measured regional cerebral blood flow (rCBF) with 15O-labeled water and positron emission tomography (PET). To detect areas with changes of rCBF during bimanual finger movements of different characteristics, we studied 12 right-handed normal volunteers. A complete session consisted of three rest scans and six scans with acoustically paced (1 Hz) bimanual, mirror, or parallel sequential finger movements. Activation of the right dorsal premotor area (PMd) extending to the posterior supplementary motor area (SMA) was significantly stronger during the parallel movements than during the mirror sequential movements (p < 0.05, at cluster level with correction for multiple comparisons). To determine whether these cortical areas truly represented bimanual coordination, a different group of nine normal volunteers was studied with a different task. Subjects performed acoustically paced (2 Hz) abduction-adduction movements of the index finger, making right only, left only, and bimanual mirror and parallel movements. Activation of the posterior SMA and right PMd was significantly greater during the parallel movements than during the bimanual mirror movements or the unimanual movements of either hand (p < 0.01, with anatomical constraint). Thus, the posterior SMA and right PMd appear to be related to the bimanual coordination of finger movements.

To study neuronal activities that influence the generation of the alpha rhythm, we used positron emission tomography and simultaneous recording of the electroencephalogram (EEG) in normal volunteers and under passive conditions. A negative correlation between regional cerebral blood flow and alpha power was found in the occipital cortex, consistent with the visual modality-specific reactivity of the alpha rhythm. A positive correlation was found in the pons, midbrain, hypothalamus, amygdala, the basal prefrontal cortex, insula and the right dorsal premotor cortex. Neuronal activities of the brain stem and limbic system that are positively correlated with alpha power may provide an anatomical basis for studies of the relationship between emotional state and brain rhythm in health and disease.