title: Metabolic studies of [18F-alpha-methyl]tyrosine in mice bearing colorectal carcinoma LS-180.
abstract: Brain and tumor uptake of [18F-alpha-methyl]tyrosine (18F-AMT) and the incorporation into each of four fractions (lipid, RNA, DNA and protein) were investigated in mice bearing LS180 colorectal carcinoma. Homogenized tissues were analyzed by the fractionation method into an acid-soluble fraction (ASF) and an acid-precipitable fraction (APF). The APF was further investigated to assess the incorporation of 18F-AMT into each fraction. Incorporation into four fractions of brain and tumor at 60 min post-injection was 20 and 12%, respectively; 10% of the activity was incorporated to lipid in brain and 5% in tumor. There was 5, 2 and 2% incorporation with RNA, DNA and protein, respectively. Metabolites in ASF were analyzed by high-performance liquid chromatography and thin-layer chromatography. There was only one radioactive peak, which corresponded to 18F-AMT. The incorporation of 18F-AMT into lipid was twice that of 18F-AMT in tumor. The uptake of 18F-AMT in tissues was rapid and accomplished before 30 min, and then slowly diffused in blood. These results implied that 18F-AMT was metabolized to protein to only a small extent and trapped as intact 18F-AMT in cells up to 60 min. We conclude that 18F-AMT is a promising tracer for tumor imaging and quantification of the transport rate using two-compartment models.
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D019275:Radiopharmaceuticals / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014055:Tomography, Emission-Computed; D014407:Tumor Cells, Cultured; D019805:alpha-Methyltyrosine / Q000378:metabolism* / Q000493:pharmacokinetics