Method of Labeling Flumazenil with F-18 and Separating and Purifying F-18-Flumazenil

摘要

Flumazenil (FMZ) is labeled with fluorine(F)-18 to obtain F-18-flumazenil. F-18-flumazenil can be strongly combined with type-A acceptor of gamma-aminobutyric acid (GABAA) in brain for tracing. The time and temperature for labeling is saved and lowered. The toxic chemical, acetonitrile, used in separation and purification can be prevented. The present invention has a simplified procedure for evaluating mental disease medicines in a short time. Moreover, time for developing medicines for treating related diseases of the central nervous system can be reduced.

主权项

1. A method of labeling flu mazenil (FMZ) with fluorine(F)-18 and separating and purifying F-18-flumazenil, comprising steps of:
(a) adding a potassium carbonate (K2CO3) solution, a cryptand (Kryptofix 2.2.2.) solution, a precursor (Nitromazenil) solution, an acetonitrile (ACN) solution and an injection water into a first to a fifth tubes, respectively; (b) preparing a plurality of sixth tubes by washing with methanol once and being dried; (c) obtaining 0.2 milli-liters (mL) of a F-18 (18F/H218O) solution with activity and dose calculated; (d) processing a fluorine-oxide (F—O) separation to said F-18 solution through an ion exchange resin to adhere F-18 on said ion exchange resin and collecting residual solution in one of said sixth tubes; (e) directing said K2CO3 solution in said first tube to wash down F-18 adhered on said ion exchange resin into another one of said sixth tubes to obtain a labeling tube; (f) directing said cryptand solution in said second tube into said labeling tube and heating said labeling tube; (g) directing said ACN solution in said fourth tube into said labeling tube and heating said labeling tube; (h) after cooling down said labeling tube, processing blowing and sucking with nitrogen; (i) directing said precursor solution in said third tube into said labeling tube and heating said labeling tube to process reaction at a temperature between 120˜180 celsius degrees (° C.) for 12˜18 minutes (min); (j) after cooling down said labeling tube, directing said injection water in said fifth tube to dilute a product obtained after said reaction processed in step (i) and directly collecting said diluted product into another one of said sixth tubes to obtain a collecting tube; (k) separating and purifying said product in said collecting tube by using semi-preparative high performance liquid chromatography (HPLC); and (l) filtering said product, F-18-flumazenil, with a syringe filter to remove impurities and bacteria and storing said filtered product, F-18-flumazenil, in a sterile tube.