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Carbon-11 Formaldehyde: Development of radiolabeling technique for carbon-11 labeled peptides
https://repo.qst.go.jp/records/71868
https://repo.qst.go.jp/records/718689fbefdba-46dc-4e3b-9712-90661f7ff980
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-11-25 | |||||
| タイトル | ||||||
| タイトル | Carbon-11 Formaldehyde: Development of radiolabeling technique for carbon-11 labeled peptides | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Hanyu, Masayuki
× Hanyu, Masayuki× Sugyou, Aya× Tsuji, Atsushi× Kawamura, Kazunori× Saga, Tsuneo× Zhang, Ming-Rong× Fukumura, Toshimitsu× 破入 正行× 須尭 綾× 辻 厚至× 河村 和紀× 佐賀 恒夫× 張 明栄× 福村 利光 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives Some low molecular weight oligopeptides have been considered as potential imaging agents because they possessed good permeability properties that could permit rapid access to the target tissues. Radiolabeled peptides are becoming increasingly important in nuclear oncology, where they are used in the diagnosis and treatment of several different cancers. One of the main challenges of PET for radiochemists is the development of rapid synthetic methods for the introduction of short-lived positron-emitting radionuclides into the peptide of interest. [11C]Formaldehyde has been used as a carbon-11 labeling agent for compounds required in PET studies. Several methods have been reported for the preparation of [11C]formaldehyde from [11C]MeOH by metal catalysis. For the reasons, the use of [11C]formaldehyde has not been developed to any great extent because the current labeling approaches using [11C]formaldehyde are generally inaccessible. Hooker et al. [1] recently reported the development of a facile method for the preparation of [11C]formaldehyde. Furthermore, the treatment of tryptamine with [11C]formaldehyde under acidic conditions provided [11C]2,3,4,9-tetrahydro-1H--carboline in a good radiochemical yield. We envisaged that the treatment of Trp or Cys with [11C]formaldehyde under acidic conditions would provide [1-11C]1,2,3,4-tetrahydro--carboline-3-carboxylic acid ([1-11C]Tpi, [11C]1) or [2-11C]ThioPro [11C]2 as well as several related analogues, respectivily. Herein, we report the synthesis of carbon-11 radiolabeled oligopeptides via a cyclic reaction using [11C]formaldehyde [2, 3]. \nResults and Discussion The synthesis of [11C]1 was initially examined under the traditional acid catalyzed Pictet-Spengler conditions (cyclic reaction) using Trp and a solution of [11C]formaldehyde in DMF. The radiosynthesis of [11C]1 was conducted by mixing a solution of [11C]formaldehyde in DMF with a solution TsOH in DMF, and using Trp instead of tryptamine according to the previously described method [1]. The desired product was obtained with a moderate radiochemical conversion (RCC: 42.3±3.2%). Next, we proceeded to evaluate the Pictet-Spengler reaction using 1 mol/L HCl as the reaction solvent. Under these reaction conditions, the RCC of [11C]1 was found to be similar to those reported above. Interestingly, the Pictet-Spengler reaction was found to proceed smoothly when an aqueous solution of Trp•HCl was used without the addition of an acid catalyst to give the desired product in a 45.2% RCC. In the current study, the Pictet-Spengler reaction between [11C]formaldehyde and Trp•HCl was found to proceed in the absence of an additional acid catalyst when the materials were heated in aqueous DMF. The radiosynthesis of [11C]2 was conducted by mixing a solution of [11C]formaldehyde in DMF with Cys•HCl aqueous solution. The desired product was obtained with a RCC (73.4±4.6%). Thus, when Cys•HCl was used, it effectively provided the acid catalyst under trace amounts of [11C]formaldehyde. This procedure represents an effective radiolabeling method because it requires particularly mild conditions. Cyclic RGD peptides, such as cyclo[Arg-Gly-Asp-D-Tyr-Lys], are potent antagonists for the v3 integrin receptor. A variety of different cyclic RGD peptides conjugated to a radioactive tracer have been reported for the PET imaging of tumors that over-express the v3 integrin receptor. With this in mind and to establish further potential uses for our new labeling method, we investigated the application of our direct labeling method using [11C]formaldehyde to the model cyclic RGD peptide cyclo[Arg-Gly-Asp-D-Tyr-Lys(Trp)] •HCl (3). The reaction of compound 3 with [11C]formaldehyde under the conventional manual synthetic procedure proceeded smoothly to give the desired product cyclo[Arg-Gly-Asp-D-Tyr-Lys(1-[11C]Tpi)] ([11C]4) with a RCC of 22.3±4.3%. Interestingly, the guanidino, phenolic hydroxy, carboxylic acid and amide groups of cyclic RGD peptide remained intact under the reaction conditions. Although this method needs an oligopeptide having Trp residue on the terminal site except for the C-terminal side, a Trp residue can be easily introduced to the epsilon amino group of Lys residue or N-terminal amino acid residue. Based on this result, it is therefore clear that this procedure could be particularly effective for the direct formation of cyclic C-C bonds for the radiolabeling of oligopeptides. Further details about studies by remote-controlled radiosynthesis and PET will be reported. We have successfully achieved the preparation of [11C]4 via a Pictet-Spengler reaction. This labeling reaction was completed under mild reaction conditions over a short reaction time in only one step using the HCl salt of the precursor without the need for a protecting group. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Ninth Japan-China Joint Seminar on Radiopharmaceutical Chemistry | |||||
| 発表年月日 | ||||||
| 日付 | 2015-11-09 | |||||
| 日付タイプ | Issued | |||||
