Hasler P H, Beer H F, Frey L, Rossetti I, Schubiger P A
Radiopharmacy Division, Paul Scherrer Institute, Villigen PSI, Switzerland.
J Nucl Biol Med (1991). 1994 Dec;38(4 Suppl 1):59-62.
The selective, reversible inhibitor of monoamine oxidase B (MAO-B), Ro 19-6327 (Lazabamide) N-aminoethyl-5-chloro-picolinamide, inhibits the enzyme with an initial competitive phase, followed by a time-dependent inhibition of MAO-B; i.e. Ro 19-6327 is a substrate for MAO-B, and after its oxidation it is activated into an intermediate form which remains tightly bound to the enzyme's active site. Our radiopharmaceutical is a new 123I-labelled derivative of Ro 19-6327, N-aminoethyl-5-[123I]iodo-picolinamide, which seems to be a potentially useful SPECT tracer for the imaging of the MAO-B enzyme distributions. The first biodistribution of this compound was measured in rats at 6 different points in time (10, 25, 40, 60, 180 and 900 minutes post-injection). For each point the average from three animals was taken. In the brain there was an activity plateau over the first hour. In the first hour post-injection the brain-to-blood ratio was over 1, with a maximum ratio of 1.24 at 25 minutes post-injection. Because MAO-B is abundant in the ependyma, pineal and cerebellar Bergmann glia cells, this ratio of 1.24 over the whole brain is encouraging. At first, radioactivity was principally and rapidly accumulated in the liver. After 1 hour, about 37% of the injected activity is accumulated there. The elimination of the compound seemed to take place mainly through the hepatobiliary system (about 75%), but also via the kidneys (about 25%). Fifteen hours post-injection, only 4% (corrected for decay) of the injected radioactivity was left in the body.(ABSTRACT TRUNCATED AT 250 WORDS)
单胺氧化酶B（MAO - B）的选择性、可逆抑制剂Ro 19 - 6327（拉扎酰胺），即N - 氨基乙基 - 5 - 氯 - 吡啶甲酰胺，以初始竞争阶段抑制该酶，随后对MAO - B产生时间依赖性抑制；也就是说，Ro 19 - 6327是MAO - B的底物，其氧化后被激活为一种中间形式，该形式与酶的活性位点紧密结合。我们的放射性药物是Ro 19 - 6327的一种新的123I标记衍生物，即N - 氨基乙基 - 5 - [123I]碘 - 吡啶甲酰胺，它似乎是一种潜在有用的SPECT示踪剂，用于MAO - B酶分布成像。在大鼠中于6个不同时间点（注射后10、25、40、60、180和900分钟）测量了该化合物的首次生物分布。每个时间点取三只动物的平均值。在大脑中，注射后的第一个小时内活性保持平稳。注射后第一个小时，脑血比超过1，在注射后25分钟时最大比值为1.24。由于MAO - B在室管膜、松果体和小脑伯格曼胶质细胞中含量丰富，整个大脑1.24的这个比值令人鼓舞。起初，放射性主要且迅速在肝脏中积累。1小时后，约37%的注射活性积累在肝脏中。该化合物的消除似乎主要通过肝胆系统（约75%），但也通过肾脏（约25%）。注射后15小时，体内仅留存4%（经衰变校正）的注射放射性。（摘要截断于250字）
