Development of a novel site-specific 18F protein labeling method and application for synthesis of 18F-EGF

• Project/Area Number: 23791465
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Kumamoto University (2012-2013); The Institute of Physical and Chemical Research (2011)
• Principal Investigator: HASEGAWA Koki 熊本大学, 生命科学研究部, 助教 (50525798)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: EGF / 上皮性腫瘍 / SPECT / 67Ga / 分子イメージング / 分子病理診断 / タンパク製剤 / 染色 / PET / 放射標識 / PETプローブ / N末端特異的標識

Research Abstract

We prepared NODAGA-EGF as a molecular probe and set up the molecular imaging device in Kumamoto University. EGF, which consists of 53 amino acid residues, was synthesized by Fmoc solid-phase method. After elongation of peptide chain, NODAGA(tBu)3 was introduced at N-terminus. Fully protected peptide resin was treated in TFA solution to cleave from resin and remove protection groups. After HPLC purification, disulfide bonds were formed to give the labeling precursor. Next, to perform molecular imaging study, SPECT/CT was set up. We established a method to form stable complex with Ga-67 via DOTA chelator. SPECT device was checked the accuracy of quantification and image resolution. SPECT imaging using 67Ga-DOTA-octreotate was carried out on the mouse implanted with small cell lung tumor cell (H69). As the result, we could observe the accumulation of the Ga-67 in H69 tumor.

Research Products

• [Journal Article] Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with ^<68>Ga-DOTA-octreotide : A potential PET tracer for beta cell mass measurement (2013) (2013)
  • Author(s): Sako, T., Hasegawa, K., Nishimura, M., Kanayama, Y., Wada, Y., Hayashinaka, E., Cui, Y., Kataoka, Y., Senda, M., Watanabe, Y.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 442 (1-2) Pages: 79-84
  • Peer Reviewed
• [Journal Article] Novel molecular imaging of atherosclerosis with Gallium-68-labeled Apolipoprotein A-I mimetic peptide and positron emission Tomography (2013) (2013)
  • Author(s): Kawachi, E., Uehara, Y., Hasegawa, K., Yahiro, E., Ando, S., Wada, Y., Yano, T., Nishikawa, H., Shiomi, M., Miura, S., Watanabe, Y., Saku, K.
  • Journal Title: Circulation Journal Volume: 77 (6) Pages: 1482-1489
  • Peer Reviewed
• [Journal Article] Detection of early stage atherosclerotic plaques using PET and CT fusion imaging targeting P-selectin in low density lipoprotein receptor-deficient mice (2013) (2013)
  • Author(s): Nakamura, I., Hasegawa, K., Wada, Y., Hirase, T., Node, K., Watanabe, Y.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 433 (1) Pages: 47-51
  • Peer Reviewed
• [Journal Article] Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with 68Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement (2013)
  • Author(s): Sako T, Hasegawa K, Nishimura M, Kanayama Y, Wada Y, Hayashinaka E, Cui Y, Kataoka Y, Senda M, and Watanabe Y
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 442 Issue: 1-2 Pages: 79-84
  • DOI: 10.1016/j.bbrc.2013.11.001
  • Peer Reviewed
• [Journal Article] Detection of early stage atherosclerotic plaques using PET and CT fusion imaging targeting P-selectin in low density lipoprotein receptor-deficient mice (2013)
  • Author(s): Nakamura I, Hasegawa K, Wada Y, Hirase T, Node K, Watanabe Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 433 Issue: 1 Pages: 47-51
  • DOI: 10.1016/j.bbrc.2013.02.069
  • Peer Reviewed
• [Journal Article] Novel Molecular Imaging of Atherosclerosis With Gallium-68-Labeled Apolipoprotein A-I Mimetic Peptide and Positron Emission Tomography (2013)
  • Author(s): Kawachi E, Uehara Y, Hasegawa K, Yahiro E, Ando S, Wada Y, Yano T, Nishikawa H, Shiomi M, Miura S, Watanabe Y, Saku K.
  • Journal Title: Circulation Journal Volume: 77 Issue: 6 Pages: 1482-1489
  • DOI: 10.1253/circj.CJ-12-0736
  • NAID: 130003361654
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Presentation] パラフィン包埋切片を用いた低分子リガンドによる受容体染色法の開発 (2013)
  • Author(s): 長谷川功紀,伊藤隆明
  • Organizer: 日本組織細胞化学会総会
  • Place of Presentation: 東京・航空会館
  • Year and Date: 2013-09-28
• [Presentation] パラフィン包埋切片を用いた低分子リガンドによる受容体染色法の開発 (2013)
  • Author(s): 長谷川功紀, 伊藤隆明
  • Organizer: 第54回日本組織細胞化学会総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Mutant epidermal growth factor receptor reduces expression of Notch receptors and modifies lung epithelial differentiation (2012)
  • Author(s): Koki Hasegawa, Hiroki Kameyama, Shinji Kudoh, Wael Hassan, Kanako Niimori-Kita, Takaaki Ito
  • Organizer: 14th International Congress of Histochemistry and Cytochemistry
  • Place of Presentation: Kyoto, Japan
• [Presentation] [^<68>Ga]DOTA-FAMPの合成と動脈硬化性プラークのPET研究 (2011)
  • Author(s): 長谷川功紀、川内絵未、桑原廉、八尋英二、林中恵美、和田康弘、矢野恒夫、上原吉就、三浦伸一郎、朔啓二郎、渡辺恭良
  • Organizer: 第48回ペプチド討論会
  • Place of Presentation: 札幌・札幌コンベンションセンター
• [Book] 生体高分子のPETイメージングとその応用:薬剤開発促進,疾病の早期診断,薬剤の効果判定法開発を目指して (2011)
  • Author(s): 長谷川功紀
  • Publisher: Isotope news
• [Remarks]
  • URL: http://srv02.medic.kumamoto-u.ac.jp/dept/patho1/index.htm