Investigation into 64Cu-labeled Bis(selenosemicarbazone) and Bis(thiosemicarbazone) complexes as hypoxia imaging agents
| Autor: | Paul McQuade, Katherine E. Martin, Michael J. Went, Michael J. Welch, Thomas C. Castle, Philip J. Blower, Jason S. Lewis |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Biodistribution Metabolic Clearance Rate Stereochemistry Mammary Neoplasms Animal Alkylation Mice chemistry.chemical_compound In vivo Cell Line Tumor medicine Animals Tissue Distribution Radiology Nuclear Medicine and imaging Semicarbazone Diimine Semicarbazones Mice Inbred BALB C Chemistry Hypoxia (medical) Cell Hypoxia In vitro Oxygen Copper Radioisotopes Organ Specificity Isotope Labeling Positron-Emission Tomography Molecular Medicine Female Radiopharmaceuticals medicine.symptom Selectivity Nuclear chemistry |
| Zdroj: | Nuclear Medicine and Biology. 32:147-156 |
| ISSN: | 0969-8051 |
| DOI: | 10.1016/j.nucmedbio.2004.10.004 |
| Popis: | Background Cu-diacetyl-bis( N 4 -methylthiosemicarbazone) [Cu-ATSM], although excellent for oncology applications, may not be suitable for delineating cardiovascular or neurological hypoxia. For this reason, new Cu hypoxia positron emission tomography (PET) imaging agents are being examined to search for a higher selectivity for hypoxic or ischemic tissue at higher oxygen concentrations found in these tissues. Two approaches are to increase alkylation or to replace the sulfur atoms with selenium, resulting in the formation of selenosemicarbazones. Methods Three 64 Cu-labeled selenosemicarbazone complexes were synthesized and one was screened for hypoxia selectivity in vitro using EMT-6 mouse mammary carcinoma cells. Rodent biodistribution and small animal PET images were obtained from BALB/c mice implanted with EMT-6 tumors. One alkylated thiosemicarbazone was synthesized and examined. Results Of the three bis(selenosemicarbazone) ligands synthesized and examined, only 64 Cu-diacetyl-bis(selenosemicarbazone) [ 64 Cu-ASSM] was isolated in high-enough radiochemical purity to undertake cell uptake experiments where uptake was shown to be independent of oxygen concentration. The bis(thiosemicarbazone) complex synthesized, 64 Cu-diacetyl-bis( N 4 -ethylthiosemicarbazone) [ 64 Cu-ATSE], showed hypoxia selectivity similar to 64 Cu-ATSM although at a higher oxygen concentration. Biodistribution studies for 64 Cu-ASSM and 64 Cu-ATSE showed high tumor uptake at 20 min ( 64 Cu-ASSM, 10.33±0.78% ID/g; 64 Cu-ATSE, 7.71±0.46% ID/g). PET images of EMT-6 tumor-bearing mice visualized the tumor with 64 Cu-ATSE and revealed hypoxia selectivity consistent with the in vitro data. Conclusion Of the compounds synthesized, only 64 Cu-ASSM and 64 Cu-ATSE could be examined in vitro and in vivo. Although the stability of bis(selenosemicarbazone) complexes increased upon addition of methyl groups to the diimine backbone, the fully alkylated species, 64 Cu-ASSM, demonstrated no hypoxia selectivity. However, the additional alkylation present in Cu-ATSE modifies the hypoxia selectivity and in vivo properties when compared with Cu-ATSM. |
| Databáze: | OpenAIRE |
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