Development novel fluorine-18 labeled artificial amino acid radiopharmaceutical as a tumor seeking PET molecular imaging based on system A amino acid transport

• Project/Area Number: 23791478
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Research Institute, Shiga Medical Center
• Principal Investigator: KAGAWA SHINYA 滋賀県立成人病センター(研究所), その他部局等, 主任研究員 (10393191)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: アミノ酸 / アミノ酸輸送システムL / [11C]MET / アミノ酸輸送システムA / [11C]MeAIB / PET / [18F]NMeFAMP / C-11 MET / C-11 MeAIB / F-18 NMeFAMP

Research Abstract

We have developed [N-methyl-11C]alpha-methylaminoisobutyric acid ([11C]MeAIB) PET imaging as a tumor seeking molecular imaging based on system A amino acid transport. The aim of this study was to develop a new artificial amino acid radiopharmaceutical labeled with fluorine-18, which has longer half-life (109 min) than carbon-11 (20 min) and would be widely available in clinical use. To develop novel fluorine-18 labeled tracers, we focused on alpha-Methyl-DL-serine as a starting material. And then we developed a precursor, (R)-3,4-Dimethyl-1,2,3-oxathiazolidine-4-carboxylic acid tert-butyl ester 2,2-dioxide. Labeling of (R)-3-[18F]Fluoro-2-methyl-2-N-(methylamino)propanoic acid ([18F]NMeFAMP) which are fluorinated analogues of MeAIB was carried out conveniently and efficiently in a short period of time (within 90 min). After the purification, [18F]NMeFAMP was obtained with a radiochemical purity greater than 99.9%.

Research Products

• [Journal Article] Assessment of [^<18>F]-fluoroacetate PET/CT as a tumor-imaging modality : preclinical study in healthy volunteers and clinical evaluation in patients with liver tumor (2014)
  • Author(s): Takemoto K, Hatano E, Nishii R, Kagawa S, Kishibe Y, Takahashi M, Yamauchi H, Matsumura K, Zaima M, Toriguchi K, Tanabe K, Kitamura K, Seo S, Taura K, Endo K, Uemoto S, Higashi T.
  • Journal Title: Ann Nucl Med Volume: 28(4) Pages: 371-80
• [Journal Article] Monitoring of gefitinib sensitivity with radioiodinated PHY based on EGFR expression (2014)
  • Author(s): Yoshimoto M, Hirata M, Kanai Y, Naka S, Nishii R, Kagawa S, Kawai K, Ohmomo Y.
  • Journal Title: Biol Pharm Bull Volume: 37(3) Pages: 355-60
  • NAID: 130003390939
• [Journal Article] Assessment of [18F]-fluoroacetate PET/CT as a tumor-imaging modality: preclinical study in healthy volunteers and clinical evaluation in patients with liver tumor. (2014)
  • Author(s): ① Takemoto K, Hatano E, Nishii R, Kagawa S, Kishibe Y, Takahashi M, Yamauchi H, Matsumura K, Zaima M, Toriguchi K, Tanabe K, Kitamura K, Seo S, Taura K, Endo K, Uemoto S, Higashi T.
  • Journal Title: Annals of Nuclear Medicine Volume: 28 Issue: 4 Pages: 371-380
  • DOI: 10.1007/s12149-014-0823-z
  • Peer Reviewed
• [Journal Article] Monitoring of gefitinib sensitivity with radioiodinated PHY based on EGFR expression. (2014)
  • Author(s): Yoshimoto M, Hirata M, Kanai Y, Naka S, Nishii R, Kagawa S, Kawai K, Ohmomo Y.
  • Journal Title: Biol Pharm Bull. Volume: 37 Pages: 355-60
  • NAID: 130003390939
  • Peer Reviewed
• [Journal Article] Impaired perfusion modifies the relationship between blood pressure and stroke risk in major cerebral artery disease (2013)
  • Author(s): Yamauchi H, Higashi T, Kagawa S, Kishibe Y, Takahashi M.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 84(11) Pages: 1226-32
• [Journal Article] Diagnostic usefulness of an amino acid tracer,α-[N-methyl-(11)C]- methylaminoisobutyric acid ((11)C-MeAIB), in the PET diagnosis of chest malignancies (2013)
  • Author(s): Nishii R, Higashi T, Kagawa S, Kishibe Y, Takahashi M, Yamauchi H, Motoyama H, Kawakami K, Nakaoku T, Nohara J, Okamura M, Watanabe T, Nakatani K, Nagamachi S, Tamura S, Kawai K, Kobayashi M.
  • Journal Title: Ann Nucl Med Volume: 27(9) Pages: 808-21
• [Journal Article] A useful EGFR-TK ligand for tumor diagnosis with SPECT : development of radioiodinated 6-(3-morpholinopropoxy)-7-ethoxy-4-(3'-iod ophenoxy)quinazoline (2013)
  • Author(s): Hirata M, Kanai Y, Naka S, Yoshimoto M, Kagawa S, Matsumuro K, Katsuma H, Yamaguchi H, Magata Y, Ohmomo Y.
  • Journal Title: Ann Nucl Med Volume: 27(5) Pages: 431-43
  • NAID: 10031183404
• [Journal Article] Chronic hemodynamic compromise and cerebral ischemic events in asymptomatic or remote symptomatic large-artery intracranial occlusive disease (2013)
  • Author(s): Yamauchi H, Higashi T, Kagawa S, Kishibe Y, Takahashi M.
  • Journal Title: AJNR Am J Neuroradiol Volume: 34(9) Pages: 1704-10
• [Journal Article] Imaging epigenetic regulation by histone deacetylases in the brain using PET/MRI with ^<18>F-FAHA (2013)
  • Author(s): Yeh HH, Tian M, Hinz R, Young D, Shavrin A, Mukhapadhyay U, Flores LG, Balatoni J, Soghomonyan S, Jeong HJ, Pal A, Uthamanthil R, Jackson JN, Nishii R, Mizuma H, Onoe H, Kagawa S, Higashi T, Fukumitsu N, Alauddin M, Tong W, Herholz K, Gelovani JG.
  • Journal Title: Neuroimage Volume: 1(64) Pages: 630-9
• [Journal Article] Impaired perfusion modifies the relationship between blood pressure and stroke risk in major cerebral artery disease. (2013)
  • Author(s): Yamauchi H, Higashi T, Kagawa S, Kishibe Y, Takahashi M.
  • Journal Title: J Neurol Neurosurg Psychiatry. Volume: 84 Issue: 11 Pages: 1226-32
  • DOI: 10.1136/jnnp-2013-305159
  • Peer Reviewed
• [Journal Article] Diagnostic usefulness of an amino acid tracer, α-[N-methyl- ^11C]-methylaminoisobutyric acid ( ^<11>C-MeAIB), in the PET diagnosis of chest malignancies (2013)
  • Author(s): Nishii R, Higashi T, Kagawa S, Kishibe Y, Takahashi M, Yamauchi H, Motoyama H, Kawakami K, Nakaoku T, Nohara J, Okamura M, Watanabe T, Nakatani K, Nagamachi S, Tamura S, Kawai K, Kobayashi M
  • Journal Title: Ann Nucl Med Volume: 27(9) Issue: 9 Pages: 808-21
  • DOI: 10.1007/s12149-013-0750-4
  • Peer Reviewed
• [Journal Article] A useful EGFR-TK ligand for tumor diagnosis with SPECT: development of radioiodinated 6-(3-morpholinopropoxy)-7-ethoxy-4-(3'-iodophenoxy)quinazoline. (2013)
  • Author(s): Hirata M, Kanai Y, Naka S, Yoshimoto M, Kagawa S, Matsumuro K, Katsuma H, Yamaguchi H, Magata Y, Ohmomo Y.
  • Journal Title: Ann Nucl Med. Volume: 27 Issue: 5 Pages: 431-443
  • DOI: 10.1007/s12149-013-0703-y
  • NAID: 10031183404
  • Peer Reviewed
• [Journal Article] Imaging epigenetic regulation by histone deacetylases in the brain using PET/MRI with (18)F-FAHA (2013)
  • Author(s): Yeh HH et al.
  • Journal Title: Neuroimage Volume: 64 Pages: 630-639
  • DOI: 10.1016/j.neuroimage.2012.09.019
  • Peer Reviewed
• [Journal Article] Is misery perfusion still a predictor of stroke in symptomatic major cerebral artery disease? (2012)
  • Author(s): Yamauchi H, Higashi T, Kagawa S, Nishii R, Kudo T, Sugimoto K, Okazawa H, Fukuyama H.
  • Journal Title: Brain Volume: 135(8) Pages: 2515-26
• [Journal Article] ynthesis and evaluation of radioiodinated phenoxyquinazoline and benzylaminoquinazoline derivatives as new EGF receptor tyrosine kinase imaging ligands for tumor diagnosis using SPECT (2012)
  • Author(s): Hirata M, Kanai Y, Naka S, Matsumuro K, Kagawa S, Yoshimoto M, Ohmomo Y.
  • Journal Title: Ann Nucl Med Volume: 26(5) Pages: 381-9
• [Journal Article] Is misery perfusion still a predictor of stroke in symptomatic major cerebral artery disease? (2012)
  • Author(s): Yamauchi H, Higashi T, Kagawa S, Nishii R, Kudo T, Sugimoto K, Okazawa H, Fukuyama H
  • Journal Title: Brain Volume: 135 Issue: 8 Pages: 2515-2526
  • DOI: 10.1093/brain/aws131
  • Peer Reviewed
• [Journal Article] A dual fluorinated and iodinated radiotracer for PET and SPECT imaging ofβ-amyloid plaques in the brain (2011)
  • Author(s): Watanabe H, Ono M, Kimura H, Kagawa S, Nishii R, Fuchigami T, Haratake M, Nakayama M, Saji H.
  • Journal Title: Bioorg Med Chem Lett Volume: 21(21) Pages: 6519-22
• [Journal Article] Novel ^<18>F-labeled benzofuran derivatives with improved properties for positron emission tomography (PET) imaging ofβ-amyloid plaques in Alzheimer's brains (2011)
  • Author(s): Ono M, Cheng Y, Kimura H, Cui M, Kagawa S, Nishii R, Saji H.
  • Journal Title: J Med Chem Volume: 54(8) Pages: 2971-9
• [Presentation] 固相抽出法による製剤化技術を用いた新規アミロイドイメージング剤[^<18>F]FPYBF-2の合成検討 (2014)
  • Author(s): 加川信也、矢倉栄幸、西井龍一、東達也、山内浩、川井恵一、渡邊裕之、木村寛之、小野正博、佐治英郎
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-28
• [Presentation] 薬剤製造の現場からPET (2014)
  • Author(s): 加川信也
  • Organizer: 化学ワークショップ2014
  • Place of Presentation: 由布院
  • Year and Date: 2014-02-07
• [Presentation] 固相抽出法による製剤化技術を用いた新規アミロイドイメージング剤[18F]FPYBF-2の合成検討 (2014)
  • Author(s): 加川信也、矢倉栄幸、西井龍一、東達也、山内浩、川井恵一、渡邊裕之、木村寛之、小野正博、佐治英郎
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] 薬剤製造の現場から (2014)
  • Author(s): 加川信也
  • Organizer: PET化学ワークショップ2014
  • Place of Presentation: 兵庫
  • Invited
• [Presentation] 臨床使用に向けた新規アミロイドイメージング剤[^<18>F]FPYBF-2の合成 (2013)
  • Author(s): 加川信也、西井龍一、東達也、岸辺喜彦、高橋昌章、山内浩、川井恵一、渡邊裕之、木村寛之、小野正博、佐治英郎
  • Organizer: 第53回日本核医学会学術総会
  • Place of Presentation: 博多
  • Year and Date: 2013-11-09
• [Presentation] 新しい固相抽出技術を用いた[^<18>F]Fluoroacetate ([^<18>F]FACE)合成法の検討 (2013)
  • Author(s): 加川信也、西井龍一、東達也、山内浩、高橋和弘、水間広、尾上浩隆、竹本研史、波多野悦郎、川井恵一
  • Organizer: 第53回日本核医学会学術総会
  • Place of Presentation: 博多
  • Year and Date: 2013-11-09
• [Presentation] [^<18>F]Fluoroacetate ([^<18>F]FACE)臨床研究に向けて (2013)
  • Author(s): 加川信也、矢倉栄幸、西井龍一、東達也、岸辺喜彦、高橋昌章、山内浩、水川陽介、竹本研史、波多野悦郎、高橋和弘、水間広、尾上浩隆、川井恵一
  • Organizer: PETサマーセミナー2013
  • Place of Presentation: 金沢
  • Year and Date: 2013-08-23
• [Presentation] PET薬剤合成の勘所 (2013)
  • Author(s): 加川信也
  • Organizer: [^<18>F]フルオロ酢酸PET化学ワークショップ2013
  • Place of Presentation: 由布院
  • Year and Date: 2013-02-09
• [Presentation] Novel approach for solid-phase radiosynthesis of ^<18>F-Fluoroacetate : Comparison between one-pot and two-pot distillation procedure (2013)
  • Author(s): Shinya Kagawa, Ryuichi Nishii, Tatsuya Higashi, Hiroshi Yamauchi, Kenji Takemoto, Akiko Tachibana, Kazuhiro Takahashi, Hiroshi Mizuma, Hirotaka Onoe, Keiichi Kawai
  • Organizer: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) 60th Annual Meeting
  • Place of Presentation: VANCOUVER, BC, CANADA
• [Presentation] Radiosynthesis of [^<18>F]Fluoroacetate by a one-pot distillation procedure : a novel approach of the solid-phase synthesis (2013)
  • Author(s): Shinya Kagawa, Ryuichi Nishii, Tatsuya Higashi, Hiroshi Yamauchi, Kenji Takemoto, Etsuro Hatano, Akiko Tachibana, Kazuhiro Takahashi, Hiroshi Mizuma, Hirotaka Onoe, Shigeki Nagamachi, Keiichi Kawai, Shozo Tamura
  • Organizer: The 20th International Symposium on Radiopharmaceutical Sciences (ISRS)
  • Place of Presentation: ICC JEJU, Jeju, KOREA
• [Presentation] 新規アミロイドイメージング剤[^<18>F]FPYBF-2合成法の検討 (2013)
  • Author(s): 加川信也、矢倉栄幸、西井龍一、東達也、山内浩、川井恵一、渡邊裕之、木村寛之、小野正博、佐治英郎
  • Organizer: 第八回日本分子イメージング学会
  • Place of Presentation: 横浜
• [Presentation] 臨床使用に向けた新規アミロイドイメージング剤[18F]FPYBF-2の合成 (2013)
  • Author(s): 加川信也、西井龍一、東達也、岸辺喜彦、高橋昌章、山内浩、川井恵一、渡邊裕之、木村寛之、小野正博、佐治英郎
  • Organizer: 第53回日本核医学会学術総会
  • Place of Presentation: 博多
• [Presentation] 新しい固相抽出技術を用いた[18F]Fluoroacetate ([18F]FACE)合成法の検討 (2013)
  • Author(s): 加川信也、西井龍一、東達也、山内 浩、高橋和弘、水間広、尾上浩隆、竹本研史、波多野悦郎、川井恵一
  • Organizer: 第53回日本核医学会学術総会
  • Place of Presentation: 博多
• [Presentation] [18F]Fluoroacetate ([18F]FACE)臨床研究に向けて (2013)
  • Author(s): 加川 信也、矢倉 栄幸、西井 龍一、東 達也、岸辺 喜彦、高橋 昌章、山内 浩、水川 陽介、竹本 研史、波多野 悦郎、高橋 和弘、水間 広、尾上 浩隆、川井 恵一
  • Organizer: PETサマーセミナー2013
  • Place of Presentation: 金沢
  • Invited
• [Presentation] Novel approach for solid-phase radiosynthesis of 18F-Fluoroacetate: Comparison between one-pot and two-pot distillation procedure. (2013)
  • Author(s): Shinya Kagawa, Ryuichi Nishii, Tatsuya Higashi, Hiroshi Yamauchi, Kenji Takemoto, Akiko Tachibana, Kazuhiro Takahashi, Hiroshi Mizuma, Hirotaka Onoe, Keiichi Kawai
  • Organizer: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) 60th Annual Meeting
  • Place of Presentation: VANCOUVER
• [Presentation] Radiosynthesis of [18F]Fluoroacetate by a one-pot distillation procedure: a novel approach of the solid-phase synthesis. (2013)
  • Author(s): Shinya Kagawa, Ryuichi Nishii, Tatsuya Higashi, Hiroshi Yamauchi, Kenji Takemoto, Etsuro Hatano, Akiko Tachibana, Kazuhiro Takahashi, Hiroshi Mizuma, Hirotaka Onoe, Shigeki Nagamachi, Keiichi Kawai, Shozo Tamura
  • Organizer: The 20th International Symposium on Radiopharmaceutical Sciences (ISRS)
  • Place of Presentation: JEJU
• [Presentation] 新規アミロイドイメージング剤[18F]FPYBF-2合成法の検討 (2013)
  • Author(s): 加川信也、矢倉栄幸、西井龍一、東達也、山内浩、川井恵一、渡邊裕之、木村寛之、小野正博、佐治英郎
  • Organizer: 第八回日本分子イメージング学会
  • Place of Presentation: 横浜
• [Presentation] Radiosynthesis of [^<18>F]Fluoroacetate : Comparison between on-column hydrolysis method and two-pot distillation procedure using a cassette-type multipurpose automatic synthesizer module (2012)
  • Author(s): Shinya Kagawa, Ryuichi Nishii, Tatsuya Higashi, Hiroyo Araki, Hiroyuki Okudaira, Tomoya Uehara, Masato Kobayashi, Mitsuyoshi Yoshimoto, Yasushi Arano, Keiichi Kawai
  • Organizer: European Association of Nuclear Medicine(EANM)Congress 2012
  • Place of Presentation: イタリアミラノ
  • Year and Date: 2012-10-30
• [Presentation] [^<18>F]Fluoroacetateの合成法の開発 : オンカラム加水分解法とtwo-pot蒸留法の比較 (2012)
  • Author(s): 加川信也、西井龍一、東達也、岸辺喜彦、高橋昌章、高橋和弘、水間広、尾上浩隆、竹本研史、川井恵一、山内浩
  • Organizer: 第52回日本核医学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-10-12
• [Presentation] 臨床使用に向けた[^18F]Fluoroacetate([^18F]FACE)製造法の検討 (2012)
  • Author(s): 加川信也、矢倉栄幸、西井龍一、東達也、山内浩、水川陽介、竹本研史、波多野悦郎、高橋和弘、水間広、尾上浩隆、長町茂樹、川井恵一、田村正三
  • Organizer: 第七回日本分子イメージング学会
  • Place of Presentation: アクトシティ浜松
• [Presentation] 臨床使用に向けた[18F]Fluoroacetate（[18F]FACE）製造法の検討 (2012)
  • Author(s): 加川信也、矢倉栄幸、西井龍一、東達也、山内浩、水川陽介、竹本研史、波多野悦郎、高橋和弘、水間広、尾上浩隆、長町茂樹、川井恵一、田村正三
  • Organizer: 第七回日本分子イメージング学会
  • Place of Presentation: 浜松
• [Presentation] [18F]Fluoroacetateの合成法の開発：オンカラム加水分解法とtwo-pot蒸留法の比較 (2012)
  • Author(s): 加川信也、西井龍一、東達也、岸辺喜彦、高橋昌章、高橋和弘、水間広、尾上浩隆、竹本研史、川井恵一、山内浩
  • Organizer: 第52回日本核医学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Radiosynthesis of [18F]Fluoroacetate: Comparison between on-column hydrolysis method and two-pot distillation procedure using a cassette-type multipurpose automatic synthesizer module (2012)
  • Author(s): Shinya Kagawa, Ryuichi Nishii, Tatsuya Higashi, Hiroyo Araki, Hiroyuki Okudaira, Tomoya Uehara, Masato Kobayashi, Mitsuyoshi Yoshimoto, Yasushi Arano, Keiichi Kawai
  • Organizer: European Association of Nuclear Medicine（EANM）Congress 2012
  • Place of Presentation: ミラノ
• [Presentation] PET腫瘍診断薬[^<18>F]Fluoroacetateの合成基礎検討 (2011)
  • Author(s): 加川信也、西井龍一、東達也、岸辺喜彦、高橋昌章、山内浩、竹本研史、波多野悦郎、長町茂樹、川井恵一、田村正三
  • Organizer: 第51回日本核医学会学術総会
  • Place of Presentation: つくば
  • Year and Date: 2011-10-28
• [Presentation] がん診断に役立つPET薬剤の合成 (2011)
  • Author(s): 加川信也
  • Organizer: 開発がん診療セミナー第16回「がん診療と放射線被ばく」
  • Place of Presentation: 研究所講堂滋賀県立成人病センター
  • Year and Date: 2011-05-25
• [Presentation] Juri G Gerovani F-18フルオロ酢酸のヒト肝細胞における集積検討 (2011)
  • Author(s): 加川信也、西井龍一、竹本研史、東達也、波多野悦郎、水間広、尾上浩隆、長町茂樹、川井恵一、田村正三
  • Organizer: 第六回日本分子イメージング学会
  • Place of Presentation: 神戸国際会議場
• [Presentation] PET腫瘍診断薬[18F]Fluoroacetateの合成基礎検討 (2011)
  • Author(s): 加川信也、西井龍一、東達也、岸辺喜彦、高橋昌章、山内浩、竹本研史、波多野悦郎、長町茂樹、川井恵一、田村正三
  • Organizer: 第51回日本核医学会学術総会
  • Place of Presentation: つくば国際会議場（茨城）
• [Presentation] F-18フルオロ酢酸のヒト肝細胞における集積検討 (2011)
  • Author(s): 加川信也、西井龍一、竹本研史、東達也、波多野悦郎、水間広、尾上浩隆、長町茂樹、川井恵一、田村正三、Juri G Gerovani
  • Organizer: 第六回日本分子イメージング学会
  • Place of Presentation: 神戸国際会議場（兵庫）
• [Remarks]
  • URL: http://www.shigamed.jp/
• [Remarks] 滋賀県立成人病センター研究所
  • URL: http://www.shigamed.jp/