Interspecies variation in biodistribution of technetium (2-carbomethoxy-2-isocyanopropane)6+.
Interspecies variation in biodistribution of technetium (2-carbomethoxy-2-isocyanopropane)6+.
复制标题
锝 (2-甲氧基-2-异氰基丙烷)6 生物分布的种间差异。
DOI：
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发表时间：
1992
影响因子：
9.3
通讯作者：
Alun G. Jones
中科院分区：
文献类型：
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作者：
J. Kronauge;Noska Ma;A. Davison;B. Holman;Alun G. Jones
阳离子配合物锝（2-碳甲氧基-2-异氰丙烷）6+ (99mTc-CPI)含有末端酯基，为该化合物的体内代谢提供了途径，从而增强了其作为心肌灌注剂的性能。生物分布研究表明，该化合物在家兔、豚鼠和鸡中心肌蓄积，但在大鼠和小鼠中没有。在不同物种的血浆中99mTc-CPI体外培养后，用HPLC进行放射化学分析，证实酶解可产生许多新化合物。在25℃条件下，大鼠和小鼠血清在不到5秒的时间内完全水解，其水解率是在人、兔、豚鼠和鸡血清中观察到的水解率的500倍以上。单水解产物的化学合成和分离以及随后在豚鼠和家兔体内的生物分布研究证实，这种中性亲脂复合物不会在心脏组织中积累。由此得出结论，不同的酶体内水解速率产生了种间生物分布差异，并可能解释了相对于其他异腈配合物的中等心肌清除率。
The cationic complex technetium (2-carbomethoxy-2-isocyanopropane)6+ (99mTc-CPI) contains terminal ester groups that were included to provide a pathway for in-vivo metabolism of this compound, thereby enhancing its performance as a myocardial perfusion agent. Biodistribution studies of the compound demonstrated myocardial accumulation in rabbit, guinea pig, and chick, but not in rat and mouse. Radiochemical analysis by HPLC after in-vitro incubation of 99mTc-CPI in blood plasma from the various species confirmed enzymatic hydrolysis to numerous new compounds. Rat and mouse serum produced complete hydrolysis of this agent after incubation for less than 5 sec at 25 degrees C or rates greater than 500 times those observed in human, rabbit, guinea pig and chick serum. Chemical synthesis and isolation of the monohydrolyzed species with subsequent biodistribution studies in guinea pig and rabbit confirmed that this neutral lipophilic complex did not accumulate in heart tissue. It is concluded that varying rates of enzymatic in-vivo hydrolysis produce the interspecies biodistribution differences and may account for the moderate myocardial clearance relative to other isonitrile complexes.