Abstract
Background[11C]Methionine ([11C]MET) acts as an oncological radiopharmaceutical for measuring increased protein synthesis in brain tumours while having low uptake in normal brain an. In several Latin American countries, the official pharmacopoeias are the United States of America Pharmacopoeia (USP) and the European Pharmacopoeia (EP). For determination of the radiochemical purity, we used the monograph of L-methionine injection ([11C] methyl-methionine) of the EP (01/2002: 1617) because it is not available in the USP.We present herein an alternative methodology for the determination of the radiochemical purity, which allows the assessment of the [11C]CH3I and of the degradation radioactive products.ResultsThe proposed method enabled a greater number of impurities to be determined than could be identified using the EP method. Under the conditions proposed by EP, it is not possible to determine the presence of [11C]CH3I or other lipophilic radiochemical impurities in the final product.For the determination of enantiomeric purity according to EP a chiral thin-layer chromatography (TLC) allows the determination of D and L methionine between the established limits. This is a slow method and presents an inadequate detection due to the decay of the sample. An alternative HPLC method was optimized.ConclusionThe proposed radiochemical purity method allowed the identification of a greater number of radiochemical impurities compared to the method proposed by the EP monograph in 16 min.The proposed enantiomeric purity method enables to perform the determination in a reasonable amount of time.A discussion concerning the limit of 95% radiochemical purity proposed by the EP is necessary. If more radiochemical impurities can be detected, it is more reasonable to propose a limit of 90% for this parameter to perform clinical examinations.
Highlights
L-Methionine is an essential amino acid involved in multiple metabolic pathways
In several Latin American countries, the official pharmacopoeias are the United States of America Pharmacopoeia (USP) (The United States Pharmacopeia (USP-40) and the National Formulary (NF-25), 2017) and the European Pharmacopoeia (EP). (Council of Europe, 2014) For determination of the radiochemical purity, we used the monograph of L-methionine injection ([11C] methyl) of the EP (01/2002: 1617) because it is not available in the USP
We present an alternative methodology for the determination of the radiochemical purity, which allows the assessment of the [11C]CH3I and of the degradation radioactive products
Summary
L-Methionine is an essential amino acid involved in multiple metabolic pathways. Many tumor cells have increased expression of amino acid transporters to cover the synthesis of proteins. Methionine participates in the synthesis of different proteins as donor of methyl groups and is a precursor of cysteine and derivatives. (Jager et al, 2001; Cook et al, 1999) [11C]MET can be used in patients with gliomas to delineate uptake areas for surgery, radiotherapy, to guide biopsies, monitor and predict the response to treatments (Jacobs et al, 2005; Nuutinen et al, 2000). It has been used for other applications, such as hyperparathyroidism. One of the most common synthesis routes for routine use in clinical environments is derived from the work of Pascali et al (Pascali et al, 1999), in which the radioactive precursor [11C]CH3I is placed in a basic medium with homocysteine thiolactone in a solid support, according to Fig. 1
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