| Autor: |
Su, Z.-F., Zhang, X., Ballinger, J. R., Rauth, A. M., Pollak, A., Thornback, J. R. |
| Zdroj: |
Bioconjugate Chemistry; September 20, 1999, Vol. 10 Issue: 5 p897-904, 8p |
| Abstrakt: |
The presence of hypoxic cells in solid tumors is a marker for therapy-resistant, aggressive disease. The noninvasive detection of hypoxic cells in tumors by radiolabeled 2-nitroimidazoles is a diagnostic technique under current evaluation. Two peptidic agents, dimethylglycyl-l-seryl-l-cysteinyl-lysyl{Nε-[1-(2-nitro-1H-imidazolyl)acetamido]}glycine (RP435) and dimethylglycyl-tert-butylglycyl-l-cysteinyl-glycine-[2-(2-nitro-1H-imidazolyl)ethyl]amide (RP535) have been synthesized. Both agents contain an N3S class chelator for 99mTc and Re and a 2-nitroimidazole group which can be enzymatically reduced and selectively trapped in cells under hypoxic conditions. Two isomers of 99mTcO-RP435, which are assumed to be syn and anti conformations, were observed on HPLC analysis. The interconversion of the two isomers in aqueous solution was investigated. In contrast, RP535 chelated 99mTc to form a single isomer and no conversion to its counterpart has been observed on HPLC analysis. The tert-butyl group on the chelator may inhibit the formation and interconversion of the syn and anti isomers of 99mTcO-RP535. Both tracers showed a significant degree of hypoxia-specific accumulation in an in vitro assay, with 99mTcO-RP535 showing higher selectivity for hypoxic cells than 99mTcO-RP435. These results suggest that 99mTcO-RP535 represents a lead compound worthy of further investigation as an agent for imaging hypoxia in tumors. |
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