PRODUCTION OF 34mCl, A NEW PET RADIONUCLIDE

15th International Symposium on Radiopharmaceutical Chemistr

How to increase the reactivity of [18F]fluoroethyl bromide: [18F]fluoroethylation of amine, phenol and amide functional groups with [18F]FEtBr, [18F]FEtBr/NaI and [18F]FEtOTf

[18F]Fluoroethyl bromide ([18F]FEtBr) is a useful synthetic precursor to synthesize 18F-labeled compounds. However, the lower reactivity of [18F]FEtBr with amine, phenol and amide functional groups than that of [11C]CH3I partly limits its wide application in the synthesis of [18F]fluoroethylated compounds. The aim of this study was to increase the reactivity of [18F]FEtBr with various nucleophilic substrates for PET tracers containing amine, phenol and amide moieties. The present strategies included (1) adding NaI into the reaction mixture of [18F]FEtBr and substrate, where [18F]FEtI is reversibly formed and becomes more reactive; 2) converting [18F]FEtBr into much more reactive [18F]FEtOTf, similar to conversion of [11C]CH3I into [11C]CH3OTf. By these efforts, the [18F]fluoroethylation efficiency of various substrates containing amine, phenol and amide groups with [18F]FEtBr/NaI and [18F]FEtOTf was significantly improved, compared with the corresponding reaction efficiency with [18F]FEtBr

Quality Control of PET Radiopharmaceuticals by High-Performance Liquid Chromatography with tris(2,2\u27-bipyridyl)ruthenium(II) Electrogenerated Chemiluminescence Detection.

A highly sensitive reversed-phase liquid chromatographic (HPLC) method was investigated to analyze a range of positron emission tomography (PET) radiopharmaceuticals using electrogenerated chemiluminescence (ECL) detection. ECL is based on the reaction of PET molecules with tris(2,2-bipyridyl)ruthenium(III) [Ru(bpy)33+], which is generated through the on-line electro-oxidation of Ru(bpy)32+. In 21 different radiopharmaceuticals studied, 18 compounds could be detected with detection limits (signal-to-noise ratio = 3) of 0.12-72 ng/mL per 20 L injection. Sufficient reproducibility and linearity were obtained for the quantitative determination of PET molecules in pharmaceutical fluid. This method could be successfully applied to quality control tests of PET radiopharmaceuticals with ultra-high specific radioactivity

Development of an automated system for synthesizing 18F-labeled compounds using [18F]fluoroethyl bromide as a synthetic precursor

An automated system was developed to synthesize 18F-labeled compounds using[18F]fluoroethyl bromide ([18F]FEtBr)as a synthetic precursor. The apparatus makes possible the following sequence of processes: (1)production of an aqueous solution of [18F]fluoride([18F]F-),(2)recovery of [18F]F-from target chamber, (3)drying of [18F]F-,(4)formation and distillation of [18F]FEtBr into a trapping vessel, (5)alkylation of target compounds with [18F]FEtBr,(6)High performance liquid chromatography purification and (7)formulation. [18F]FEtBr,the synthetic precursor for fluoroethylation, was labeled via nucleophilic displacement of 2-trifluoromethanesulfonyloxy ethylbromide (BrCH2CH2OTf)with [18F]F- and was purified from the reaction mixture by distillation. After the conditions for forming [18F]FEtBr and drying [18F]F- were optimized,[18F]FEtBr was obtained in a radiochemical yield of 71+/-13%(n=21,based on [18F]F-,corrected for decay) and a radiochemical purity of 98+/-1.4% at end of the syntheses (EOS). Using this automated system,[18F]fluoroethylspiperone ([18F]FEtSP) was prepared by reacting spiperone with[18F]FEtBr in a radiochemical yield and purity of 56+/-12%(n=5,based on [18F]FEtBr, corrected for decay) and 97+/-1.5% with a specific activity of 310+/-120GBq/mumol at EOS. The total synthesis time was 55+/-2.3min from the end of bombardment and the developed system has proved to be reliable and reproducible

The simultaneous measurement method for the molar radioactivity, radiochemical purity, and chemical impurity of the [11C]choline injection

Background/Aims: [11C]Choline has been extensively used clinically for imaging prostate cancer [1]. [11C]Choline is prepared by 11C-methylation of [11C]methyl iodide and 2-dimethylaminoethanol (DMAE). It is important to determine accurately the quantity of DMAE in the final product. The most common method for the determination of the substance of [11C]choline or DMAE was by co-injection of carrier-choline or DMAE method, and by two separate analysis LC system and gas chromatography [2-4]. The quality control procedures for 11C-labeled radiopharmaceuticals is acquired rapid assessment due to short half-life radionuclide (about 20 min). Thus, we developed a rapid and simultaneous measurement method for the molar radioactivity, radiochemical purity, and chemical impurity of the [11C]choline injection using the radio-HPLC coupled with the corona-charged aerosol detector (CAD). Methods: The molar radioactivity, radiochemical purity, and chemical impurity (DMAE) of the [11C]choline injection was measured using the radio-HPLC-CAD with the post-column method. We also validated the measurement of choline and DMAE using this HPLC, and evaluated these parameters of the accuracy, precision, specificity, quantitation of limit, and linearity. Results: The molar radioactivity, radiochemical purity, and chemical impurity were over 130 GBq/μmol (over 0.1 μg/mL) at end of synthesis (EOS), over 95% at EOS, and less than 0.5 μg/mL of DMAE, respectively. In the validation, the percentages of recovery of choline and DMAE were within 100±5%. The RSD of choline and DMAE were less than 10%. Resolution between obtained choline and DMAE peak was over 1.5. The limit of quantitation of choline and DMAE was 0.1 and 0.5 μg/mL, respectively. The coefficient of correlation (R2) of choline (0.1-50 μg/mL) and DMAE (0.5-50 μg/mL) found to be >0.9999. Conclusions: We developed and optimized the simultaneous measurement method for the molar radioactivity, radiochemical purity, and chemical impurity of the [11C]choline injection using the radio-HPLC-CAD with the post-column method.References: [1] Giovacchini G, et al. Eur J Nucl Med Mol Imaging. 2017;44:1751-76. [2] Mishani E, et al. Nucl Med Biol. 2002;39:359-62. [3] Shao X, et al. Appl Radiat Isot. 2011;69:403-9. [4] Biasiotto G, et al. Med Chem. 2012;8:1182-9.\n(Abstracts are to be no more than 300 words. References, Title and authors details are not included in the word count. Abstracts should not contain bullet points.)12th World Congress of the World Federation of Nuclear Medicine and Biolog