Taylor S F, Frey K A, Baldwin R M, Papadopoulos S M, Petry N A, Rogers W L, McBride B J, Kerr J M, Kuhl D E
Department of Internal Medicine (Division of Nuclear Medicine), University of Michigan, Ann Arbor.
J Nucl Med. 1992 Oct;33(10):1836-42.
We report in vitro and in vivo preclinical studies of a new cerebral blood flow tracer, [99mTc]N1-(2-mercapto-2-methyl-propyl)-N2-(2- propargylthio-2-methylpropyl)-1,2-benzenediamine (T691). The tracer demonstrates excellent in vitro chemical stability and accumulates regionally in the brain in a pattern consistent with that of cerebral blood flow. First-pass cerebral extraction determined with the use of the brain uptake index method in the rat was 0.76. Bolus intracarotid injection in monkeys indicated a cerebral extraction of 68% and prolonged retention of 67% of the initially extracted activity. Autoradiographic studies in rats revealed a pattern characteristic of cerebral blood flow at both 1 and 60 min after systemic injection. Dynamic tomographic imaging following systemic injection in the monkey revealed peak brain activity 1 to 2 min postinjection, without significant decline over 60 min. Chromatographic studies of brain as long as 60 min following systemic injection of [99mTc]T691 showed no evidence of tracer metabolism to account for its retention. Overall, [99mTc]T691 demonstrates promise as a potential new clinical tracer of cerebral perfusion.
我们报告了一种新型脑血流示踪剂[99mTc]N1-(2-巯基-2-甲基丙基)-N2-(2-炔丙硫基-2-甲基丙基)-1,2-苯二胺（T691）的体外和体内临床前研究。该示踪剂在体外表现出优异的化学稳定性，并以与脑血流一致的模式在脑内局部蓄积。采用脑摄取指数法在大鼠中测定的首过脑摄取率为0.76。在猴中进行的颈动脉团注注射显示脑摄取率为68%，且最初摄取活性的67%有长时间滞留。在大鼠中进行的放射自显影研究显示，全身注射后1分钟和60分钟时均呈现出脑血流的特征模式。在猴中全身注射后进行的动态断层成像显示，注射后1至2分钟脑内活性达到峰值，在60分钟内无显著下降。对全身注射[99mTc]T691后长达60分钟的脑进行色谱研究，未发现示踪剂代谢以解释其滞留的证据。总体而言，[99mTc]T691作为一种潜在的新型脑灌注临床示踪剂显示出前景。
