Optimization by experimental design of precursor synthesis and radiolabeling of 2-iodo-L-phenylalanine, a novel amino acid for tumor imaging.
Various radiolabeled amino acids show promising results in tumor detection, as applied in the management of cancer patients. We synthesized the precursor 2-iodo-L-phenylalanine for easier kit labeling of [123/125I]- 2-iodo-L-phenylalanine, using the Cu1+ -assisted nucleophilic halogen exchange. Prec...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2006
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| _version_ | 1826270529271627776 |
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| author | Kersemans, V Kersemans, K Cornelissen, B Staelens, L de Spiegeleer, B Mertens, J Slegers, G |
| author_facet | Kersemans, V Kersemans, K Cornelissen, B Staelens, L de Spiegeleer, B Mertens, J Slegers, G |
| author_sort | Kersemans, V |
| collection | OXFORD |
| description | Various radiolabeled amino acids show promising results in tumor detection, as applied in the management of cancer patients. We synthesized the precursor 2-iodo-L-phenylalanine for easier kit labeling of [123/125I]- 2-iodo-L-phenylalanine, using the Cu1+ -assisted nucleophilic halogen exchange. Precursor synthesis was optimized by experimental design: Eight parameters were initially screened by a quarter fractional design. The resulting most important parameters (i.e., temperature, CuSO4, NaI) were further optimized using a full three-factor, three-level factorial design. The final conclusion for the optimal values for temperature, reaction time, and concentration of 2-bromo-L-phenylalanine, NaI, CuSO4, SnSO4, C6H6O7, and C7H6O4 were 180 degrees C, 24 hours, 61 mM, 485 mM, 10 mM, 90 mM, 90 mM, and 100 mM, respectively. The yield was increased from 39% to consistently more than 74% 2-iodo-L-phenylalanine. Structure confirmation and quality control was performed by 1H-NMR, mass spectroscopy (MS), and high-performance liquid chromatography (HPLC) (reverse phase [RP] and chiral). No phenylalanine-related impurities or racemization was detected. Subsequent radioiodination of the obtained 2-iodo-L-phenylalanine was performed in kit conditions with n.c.a. Na123/125I, resulting in a labeling yield of > 98%. After Ag-membrane filtration, a radiochemical purity of > 99% was obtained. The Cu1+ -assisted nucleophilic exchange reaction allows both routine kit preparation and "cold" synthesis of 2-iodo-L-phenylalanine from 2-bromo-L-phenylalanine. The reaction presents an interesting alternative for a cumbersome multistep, stereo-specific synthesis. |
| first_indexed | 2024-03-06T21:42:15Z |
| format | Journal article |
| id | oxford-uuid:4854ad15-d7b0-47a8-8582-b32b744acf75 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:42:15Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:4854ad15-d7b0-47a8-8582-b32b744acf752022-03-26T15:25:04ZOptimization by experimental design of precursor synthesis and radiolabeling of 2-iodo-L-phenylalanine, a novel amino acid for tumor imaging.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4854ad15-d7b0-47a8-8582-b32b744acf75EnglishSymplectic Elements at Oxford2006Kersemans, VKersemans, KCornelissen, BStaelens, Lde Spiegeleer, BMertens, JSlegers, GVarious radiolabeled amino acids show promising results in tumor detection, as applied in the management of cancer patients. We synthesized the precursor 2-iodo-L-phenylalanine for easier kit labeling of [123/125I]- 2-iodo-L-phenylalanine, using the Cu1+ -assisted nucleophilic halogen exchange. Precursor synthesis was optimized by experimental design: Eight parameters were initially screened by a quarter fractional design. The resulting most important parameters (i.e., temperature, CuSO4, NaI) were further optimized using a full three-factor, three-level factorial design. The final conclusion for the optimal values for temperature, reaction time, and concentration of 2-bromo-L-phenylalanine, NaI, CuSO4, SnSO4, C6H6O7, and C7H6O4 were 180 degrees C, 24 hours, 61 mM, 485 mM, 10 mM, 90 mM, 90 mM, and 100 mM, respectively. The yield was increased from 39% to consistently more than 74% 2-iodo-L-phenylalanine. Structure confirmation and quality control was performed by 1H-NMR, mass spectroscopy (MS), and high-performance liquid chromatography (HPLC) (reverse phase [RP] and chiral). No phenylalanine-related impurities or racemization was detected. Subsequent radioiodination of the obtained 2-iodo-L-phenylalanine was performed in kit conditions with n.c.a. Na123/125I, resulting in a labeling yield of > 98%. After Ag-membrane filtration, a radiochemical purity of > 99% was obtained. The Cu1+ -assisted nucleophilic exchange reaction allows both routine kit preparation and "cold" synthesis of 2-iodo-L-phenylalanine from 2-bromo-L-phenylalanine. The reaction presents an interesting alternative for a cumbersome multistep, stereo-specific synthesis. |
| spellingShingle | Kersemans, V Kersemans, K Cornelissen, B Staelens, L de Spiegeleer, B Mertens, J Slegers, G Optimization by experimental design of precursor synthesis and radiolabeling of 2-iodo-L-phenylalanine, a novel amino acid for tumor imaging. |
| title | Optimization by experimental design of precursor synthesis and radiolabeling of 2-iodo-L-phenylalanine, a novel amino acid for tumor imaging. |
| title_full | Optimization by experimental design of precursor synthesis and radiolabeling of 2-iodo-L-phenylalanine, a novel amino acid for tumor imaging. |
| title_fullStr | Optimization by experimental design of precursor synthesis and radiolabeling of 2-iodo-L-phenylalanine, a novel amino acid for tumor imaging. |
| title_full_unstemmed | Optimization by experimental design of precursor synthesis and radiolabeling of 2-iodo-L-phenylalanine, a novel amino acid for tumor imaging. |
| title_short | Optimization by experimental design of precursor synthesis and radiolabeling of 2-iodo-L-phenylalanine, a novel amino acid for tumor imaging. |
| title_sort | optimization by experimental design of precursor synthesis and radiolabeling of 2 iodo l phenylalanine a novel amino acid for tumor imaging |
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