CAS:24124-59-2，METHYLENE BIS(TOLUENE-4-SULFONATE)

(3R,5R)-5-(3-([F]fluoromethoxy-d2)phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl)phenyl)pyrrolidin-2-one ([F]FMPEP-d2) is a promising positron emission tomography (PET) radiopharmaceutical for the imaging of cannabinoid type 1 receptors in human studies. To facilitate widespread use of [F]FMPEP-d2 we herein report a simplified one-pot synthesis procedure that is broadly applicable for F-fluoromethylation of phenols and can be applied for routine clinical production using a commercial radiofluorination module (GE TRACERlab FX2 N). The present method overcomes previous challenges in the [F]FMPEP-d2 synthesis related to intermediate purification of a [F]fluoromethyl building block by using ditosylmethane-d2 and reacting it directly with (3R,5R)-5-(3-hydroxyphenyl)-3-[(R)-1-phenylethylamino]-1-(4-trifluoromethylphenyl)pyrrolidine-2-one in a one-pot nucleophilic reaction with [F]fluoride (K2CO3, K222, CH3CN, 80 °C, 10 min). After purification of the product by semi-preparative HPLC under isocratic conditions and formulation, [F]FMPEP-d2 was obtained in a decay-corrected radiochemical yield of 8 ± 1 %, a radiochemical purity >95 % and a molar activity of 322 ± 101 GBq/µmol in a synthesis time of 70 ± 5 min (n = 8). Validation and regulatory submission of [F]FMPEP-d2 is underway with the new methodology and will facilitate widespread human use as well as multi-center clinical trials.

The present invention relates to a method for preparing a fluorine-18-labeled fluoromethyl-substituted radiopharmaceutical using a selective azide substitution reaction that comprises: (1) obtaining a [18F]fluoride from a cyclotron through an 18O(p, n) 18F reaction; (2) separating the [18F] fluoride using an acetonitrile reaction solution containing dissolved K2,2,2 and K2CO3 to obtain a [18F] F-/H218O solution; (3) heating the [18F] F-/H218O solution to obtain K2,2,2/K18F; (4) placing the K2,2,2/K18F along with a bis(tosyloxy)methane compound into a reactor and adding a reaction solvent to cause a reaction and obtain a first precursor solution; (5) cooling the first precursor solution and adding an azide reagent to cause an azide substitution reaction and obtain a [18F]fluoromethyltosylate compound; (6) adding a bioactive molecule to the [18F]fluoromethyltosylate compound to cause an alkylation reaction and obtain a second precursor solution; and (7) adding a precursor scavenger to the second precursor solution and scavenging unreacted precursors to produce a fluorine-18-labeled fluoromethyl-substituted radiopharmaceutical.According to the present invention, the synthesis process of a radiopharmaceutical involves using a selective azide substitution reaction to inactivate the excess bis(toxyloxy)methane compound present in a crude mixture and significantly increasing the yield of alkylation of a bioactive molecular precursor and the [18F]fluoromethyltosylate compound in the subsequent step, to produce a fluorine-18-labeled fluoromethyl-substituted radiopharmaceutical with high radiochemical purity though avoiding a HPLC separation and purification process, thereby reducing the manufacturing time and cost caused by the HPLC process.

Disclosed is a molecular imaging method for evaluating liver regeneration ability after ALPPS. The method includes steps of: 1) preparing a VX2 rabbit liver cancer model; 2) performing ALPPS for the VX2 rabbit liver cancer model; 3) synthesizing 18F-Fluoromethylcholine (18F-Methylcholine, 18F-FCH); 4) PET/CT imaging and data processing for 18F-FCH. The disclosure is the first to propose the use of 18F-FCH PET/CT to monitor the proliferative capacity of residual liver, and further indirectly reflect the increased ability of cell membrane synthesis on the basis that 18F-FCH has higher choline metabolism in residual liver tissue, so that the liver regeneration ability after ALPPS is evaluated by the molecular imaging method, thereby providing important new ideas for the clinical selection of ALPPS to choose the best time for second-stage surgery.