Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “THIOSEMICARBAZONES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,621 records · Page 90Linked to original sources
PubMed2001

Copper-62 ATSM as a hypoxic tissue tracer in myocardial ischemia.

Copper-62 labeled diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) has been proposed as a generator produced positron-emitting tracer for hypoxic tissue imaging. To clarify the usefulness of 62Cu-ATSM for myocardial ischemia, 62Cu-ATSM PET was performed in 7 patients with coronary artery disease. Increased myocardial uptake of 62Cu-ATSM was observed (myocardium/blood ratio: 3.09) in one patient with unstable angina, who had increased 18F-fluorodeoxyglucose (18F-FDG) uptake under the fasting condition. The other 6 patients, who were clinically stable, did not have increased 62Cu-ATSM uptake, although abnormal 18F-FDG uptake was seen in 4 patients. This preliminary study suggests that 62Cu-ATSM is a promising PET tracer for hypoxic imaging in acute ischemia.

Aged↗
PubMed2001

Retention mechanism of hypoxia selective nuclear imaging/radiotherapeutic agent cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) in tumor cells.

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.

Animals↗
PubMed2000

Evaluation of 62Cu labeled diacetyl-bis(N4-methylthiosemicarbazone) as a hypoxic tissue tracer in patients with lung cancer.

62Cu labeled diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) has been proposed as a generator-produced, positron-emitting tracer for hypoxic tissue imaging. From basic studies, the retention mechanism of 62Cu-ATSM is considered to be closely related to cytosolic/microsomal bioreduction, a possible system for hypoxic bioreductive drug activation. In order to evaluate the characteristics of 62Cu-ATSM, PET studies were performed in 4 normal subjects and 6 patients with lung cancer. 62Cu-ATSM cleared rapidly from the blood with little lung uptake (0.43+/-0.09, uptake ratio; divided by the arterial input function) in normal subjects. Intense tumor uptake of 62Cu-ATSM was observed in all patients with lung cancer (3.00+/-1.50). A negative correlation was observed between blood flow and flow-normalized 62Cu-ATSM uptake in three of four patients. In contrast, 62Cu-ATSM uptake was not related to that of 18F-fluorodeoxyglucose. The negative correlation between blood flow and flow normalized 62Cu-ATSM uptake suggests an enhancement of retention of 62Cu-ATSM by low flow. 62Cu-ATSM is a promising PET tracer for tumor imaging, which might bring new information for chemotherapeutic treatment as well as radiotherapy of hypoxic tumors.

Adenocarcinoma↗
PubMed1999

Cytosolic/microsomal redox pathway: a reductive retention mechanism of a PET-oncology tracer, cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (cu-PTSM).

OBJECTIVE: To clarify the retention mechanism of a PET imaging agent Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-62-PTSM) in tumor cells, reductive metabolism of non-radioactive Cu-PTSM in five cultured tumor cell lines, a tumor specimen and non-tumor tissues in vitro was evaluated by electron spin resonance spectrometry (ESR). RESULTS: In the brain, mitochondrial electron transport enzyme reduced Cu-PTSM specifically. On the other hand, Cu-PTSM was not reduced in tumor mitochondria. The mitochondrial electron transport enzyme in tumor cells was not damaged, but NADH was considered to be depleted. In compensation for that, the tumor cells acquired complementary reduction activity in the microsome/cytosol. The reduction was enzymatic and NADH-dependent, possibly similar to the activation mechanism of bioreductive anticancer drugs. CONCLUSION: 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.

Animals↗
PubMed1995

Clinical application of 62Zn/62Cu positron generator: perfusion and plasma pool images in normal subjects.

We have developed a new 62Zn/62Cu positron generator, and applied it for PET imaging of perfusion and plasma volume in 5 normal subjects. The generator makes it possible by a simple procedure to obtain 62Cu eluate and labeling compounds sufficiently every 40-60 minutes. 62Cu labeled pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) was employed for cerebral and myocardial perfusion imaging and 62Cu labeled human serum albumin-dithiosemicarbazone (62Cu-HSA-DTS) was used for plasma pool imaging. The images of cerebral blood flow, cerebral plasma volume and myocardial perfusion were excellent. In addition, the analysis of tissue activity and blood activity demonstrated the microspheric character of 62Cu-PTSM. Correction of arterial activity with the standard disappearance curve of 62Cu-PTSM suggested the possibility of quantifying blood flow. The results of this study indicate the capability of the 62Zn/62Cu generator for wide clinical use without an in-house cyclotron.

Adult↗
PubMed1995

Differential mechanism of retention of Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-PTSM) by brain and tumor: a novel radiopharmaceutical for positron emission tomography imaging.

The reductive retention of 62Cu-PTSM was comparatively studied in the brain and Ehrlich ascites tumor cells by electron spin resonance spectrometry and nonradioactive Cu-PTSM. In the brain, only the mitochondrial fraction showed the ability to reduce Cu-PTSM, and the other subcellular fractions did not. In contrast, the cytosolic fraction of Ehrlich ascites tumor cells was the specific site of Cu-PTSM reduction. It was therefore considered that the retention of Cu-PTSM in the brain is closely related to mitochondrial reduction, most probably involving the mitochondrial electron transport system.

Animals↗
PubMed2003

In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM.

Tumor hypoxia is recognized as an important determinant of response to therapy. In this study we investigated the feasibility of clinical imaging with copper-60 diacetyl-bis( N(4)-methylthiosemicarbazone) ((60)Cu-ATSM) in patients with non-small-cell lung cancer (NSCLC) and also assessed whether pretreatment tumor uptake of (60)Cu-ATSM predicts tumor responsiveness to therapy. Nineteen patients with biopsy-proved NSCLC were studied by positron emission tomography (PET) with (60)Cu-ATSM before initiation of therapy. (60)Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M). All patients also underwent PET with fluorine-18 fluorodeoxyglucose (FDG) prior to institution of therapy. The PET results were correlated with follow-up evaluation (2-46 months). It was demonstrated that PET imaging with (60)Cu-ATSM in patients with NCSLC is feasible. The tumor of one patient had no discernible (60)Cu-ATSM uptake, whereas the tumor uptake in the remaining patients was variable, as expected. Response was evaluated in 14 patients; the mean T/M for (60)Cu-ATSM was significantly lower in responders (1.5+/-0.4) than in nonresponders (3.4+/-0.8) (P=0.002). However, the mean SUV for (60)Cu-ATSM was not significantly different in responders (2.8+/-1.1) and nonresponders (3.5+/-1.0) ( P=0.2). An arbitrarily selected T/M threshold of 3.0 discriminated those likely to respond to therapy: all eight responders had a T/M <3.0 and all six nonresponders had a T/M > or =3.0. Tumor SUV for FDG was not significantly different in responders and nonresponders (P=0.7) and did not correlate with (60)Cu-ATSM uptake (r=0.04; P=0.9). (60)Cu-ATSM-PET can be readily performed in patients with NSCLC and the tumor uptake of (60)Cu-ATSM reveals clinically unique information about tumor oxygenation that is predictive of tumor response to therapy.

Aged↗
PubMed2004

A DFT investigation of conformational geometries and interconversion equilibria of phenylthiosemicarbazone and its complexation with zinc.

The geometrical structures of phenylthiosemicarbazone (HAPhTSC) conformers have been obtained by geometry optimizations using density functional theory (DFT) calculations at the B3LYP/6-31G(d) and B3LYP/6-311G(d,p) levels of theory. Six thioamino and 24 thioimino tautomers of HAPhTSC have been found. Six tautomerization reactions between thioamino and thioimino tautomers occurring via transition states and their corresponding activation energies have been obtained. Conformational pathways for tautomerizations and interconversions of HAPhTSC conformers have been presented. Tautomerization between the most stable species of thioamino (Atttcc) and its thioimino (Itttcct) tautomer is an endothermic reaction, Delta H(0)=18.17 kcal mol(-1) and its log K=-13.74, at 298.15 K. Thermodynamic quantities of tautomerizations, interconversions of HAPhTSC conformers and their equilibrium constants are reported. The geometry of the zinc complex with HAPhTSC, found as a Zn(HAPhTSC)2Cl2 structure, has been obtained using B3LYP/6-31G(d) calculations. Binding of the Zn(HAPhTSC)2Cl2 complex is an exothermic and spontaneous reaction. [figure]. Conformational notation defined as a name consisting of a letter "A" for A thioamino tautomer followed by "c" for cis or "t" for trans isomerism of five dihedral angles of chi(C4-C3-C2-N3), phi(C3-C2-N3-N2), psi(C2-N3-N2-C1), theta;(N3-N2-C1-N1) and omega(N2-C1-N1-H2), serially, or a letter "I" for B thioimino tautomer followed by "c" for cis or "t" for trans isomerism of six dihedral angles of chi(C4-C3-C2-N3), phi(C3-C2-N3-N2), psi(C2-N3-N2-C1), theta(N3-N2-C1-N1), omega(N2-C1-N1-H2) and delta (N2-C1-S-H1), serially.

Computational Biology↗
PubMed1985

Binding of cis-dichlorodiammine platinum(II) to metallothionein in Ehrlich cells.

The antitumor agent, cis-dichlorodiammine Pt(II), is cytotoxic to Ehrlich cells in culture. These cells contain a substantial amount of metallothionein in the absence of inducers of the protein. At concentrations of drug which cause 60% inhibition of cell proliferation, most of the platinum is found in the cytosol. Of this about 30% is bound in the metallothionein fraction. Isolated rat liver metallothionein reacts slowly with hydrolyzed cis-dichlorodiammine Pt(II). Thus, metallothionein is a major cellular site of binding of the platinum complex at concentrations which inhibit tumor growth.

Animals↗