Development of New Noninvasive Methods of Functional Imaging Using Biologically Active Substances Labelled with Positron Emitting Radionuclides

1994 Fiscal Year Final Research Report Summary

• Project/Area Number: 04557046
• Research Category: Grant-in-Aid for Developmental Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Tohoku University
• Principal Investigator: TADA Masao Tohoku Univ., Inst.of Development, Aging and Cancer, Assoc.Prof., 加齢医学研究所, 助教授 (10006083)
• Co-Investigator(Kenkyū-buntansha): FUJIWARA Takehiko Tohoku Univ., Cyclotron and RI Center, Instr., サイクロトロンRIセンター, 助手 (70238632) ; IWATA Ren Tohoku Univ., Cyclotron and RI Center, Assoc.Prof., サイクロトロンRIセンター, 助教授 (60143038) ; KUBOTA Kazuo Tohoku Univ., Inst.of Development, Aging and Cancer, Assoc.Prof., 加齢医学研究所, 助教授 (40161674) ; SUGIYAMA Hiroshi Tohoku Univ., Inst.for Chem.Res.Sci., Assoc.Prof., 反応化学研究所, 助教授 (90006304) ; FUKUDA Hiroshi Tohoku Univ., Inst.of Development, Aging and Cancer, Prof., 加齢医学研究所, 教授 (30125645)
• Project Period (FY): 1992 – 1994
• Keywords: Synthesis / [fluoroacetyl-^<18>F]Fluoromelatonin / N^<omega>-[^<18>F]Fluoroacetylserotonin / RI / N-[^<18>F]Fluoroacetyl-D-glucosamine / 2-Deoxy-2-[^<18>F]fluoro-D-galactose / PET / Imaging

Research Abstract

1. Chemical Research
An efficient synthesis of[fluoroacetyl-^<18>F]fluoromelatonin (1) has been established. The desired isotope (1) was obtained in a 26.7% radiochemical yield. The purity, specific activity and the total time required for its synthesis are>98%, 540mCi/mmol and ca.90 min, respectively. N^<omega>-[^<18>F]Fluoroacetylserotonin (2) was also synthesized under similar conditions in 22.6% radiochemical yield. The purity and specific activity of the hormone (2) are>98% and 600mCi/mmol, respectively.
2. Medical Research
We have examined the feasibility of positron labelled radiopharmaceuticals for functional imaging.
(1). Tissue distribution of (1) has been studies using mice. The distribution was similar to that of iodolabelled melatonin which has been reported previously. It is suggested that (1)may be a useful tracer for studying the correlation of melatonin metabolism and circadian rhythm.
(2). We have studied the tumor imaging with PET using N-[^<18>F]Fluoroacetyl-D-glucosamine(3). Sugar(3) was intravenously injected through the ear vein to a Japanese white rabbit bearing a VX2 tumor in the thigh, and PET imaging was performed. Tumor was clearly visualized using (3).
(3) .Clinical PET sudy demonstrated the usefulness of 2-Deoxy-2-[^<18>F]fluoro-D-galactose for the detection of extrahepatic metastasis of hepatoma.

Research Products

• [Publications] Takehiko Fujiwara, Kazuo Kubota, Masao Tada et al.: "N-(F-18)Fluoroacetyl-D-glucosamine:A New Positron Labeled Pharmaceutical for Cancer Study," Tohoku J. Exp. Med.168. 317-321 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takehiko Fujiwara, Kazuo Kubota, Tachio Sato et al.: "The Effect of Preloaded N-Acetyl-D-glucosamine and D-Glucose on the Tissue Distribution of N-[18F]Fluoroacetyl-D-glucosamine in Tumor Bearing Rats" CYRIC Ann. Rep.1991. 188-191 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Masao Tada, Ren Iwata, Hiroshi Sugiyama et al.: "A Rapid One-pot Synthesis of [fluoroacetyl-^<18>F]Fluoromelatonin" CYRIC Ann. Rep.1992. 117-121 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Masao Tada, Ren Iwata, Hiroshi Sugiyama et al.: "A Rapid Synthesis of [fluoroacetyl-^<18>F]Fluoromelatonin(N^ω-[^<18>F]Fluoroacetyl-5-methoxy-tryptamine), a Potential Diagnostic Imaging Agent" J. Labelled Compds. Radiopharm.33. 601-606 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hiroshi Fukuda, Jutaro Takahashi, Takehiko Fujiwara et al.: "High Accumulation of 2-Deoxy-2-[^<18>F]fluoro-D-galactose by Well Differentiated Hepatomas of Mice and Rats," J. Nucl. Med.34. 780-786 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Masao Tada, Ren Iwata, Hiroshi Sugiyama et al.: "An Efficient Synthesis of N^ω-[^<18>F]-Fluoroacetylserotonin(N^ω-[^<18>F]-Fluoroacetyl-5-hydroxytryptamine)" J. Labelled Compds. Radiopharm.34. 741-746 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takehiko Fujiwara, Kazuo Kubota, Masao Tada, Masatoshi Itoh, Tachio Sato, Ren Iwata, Kazunori Sato, Hiroshi Fukuda, and Tatsuo Ido: "N- (F-18) Fluoroacetyl-D-glucosamine : A New Positron Labeled Pharmaceutical for Cancer Study" Tohoku J.Exp.Med.168. 317-321 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takehiko Fujiwara, Kazuo Kubota, Tachio Sato, Masao Tada, Ren Iwata, Masatoshi Itoh, Jutaro Takahashi, Kazunori Sato, Hiroshi Fukuda, and Tatsuo Ido: "The Effect of Preloaded N-Acetyl-D-glucosamine and D-Glucose on the Tissue Distribution of N-[18F]Fluoroacetyl-D-glucosamine in Tumor Bearing Rats" CYRIC Ann.Rep.1991. 188-191 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Masao Tada, Ren Iwata, Hiroshi Sugiyama, Kazunori Sato, Claudio Pascali, Hiroshi Fukuda, Kazuo Kubota, Roko Kubota, Hiromu Takahashi, Akira Wakui, Yoshinao Abe, Takehiko Fujiwara, Tachio Sato, and Tatsuo Ido: "A Rapid Synthesis of [fluoroacetyl-^<18>F]Fluoromelatonin (N^<omega>-[^<18>F]Fluoroacetyl-5-methoxytryptamine) , a Potential Diagnostic Imaging Agent" J.Labelled Compds.Radiopharm.33. 601-606 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Masao Tada, Ren Iwata, Hiroshi Sugiyama, Kazunori Sato, Hiroshi Fukuda, Kazuo Kubota, Roko Kubota, Hiromu Takahashi, Akira Wakui, Yoshinao Abe, Takehiko Fujiwara, Tachio Sato, and Tatsuo Ido: "A Rapid One-pot Synthesis of [fluoroacetyl-^<18>F]Fluoromelatonin" CYRIC Ann.Rep.1992. 117-121 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hiroshi Fukuda, Jutaro Takahashi, Takehiko Fujiwara, Keiichiro Yamaguchi, Yoshinao Abe, Kazuo Kubota, Tachio Sato, Hidemitsu Miyazawa, Jun Hatazawa, Masao Tada, Kiichi Ishiwata, and Tatsuo Ido: "High Accumulation of 2-Deoxy-2-[^<18>F]fluoro-D-galactose by Well Differentiated Hepatomas of Mice and Rats" J.Nucl.Med.34. 780-786 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Masao Tada, Ren Iwata, Hiroshi Sugiyama, Kazunori Sato, Hiroshi Fukuda, Kazuo Kubota, Roko Kubota, Takehiko Fujiwara, Hiromu Takahashi, Akira Wakui, and Tatsuo Ido: "An Efficient Synthesis of N^<omega>-[^<18>F]Fluoroacetylserotonin (N^<omega>-[^<18>F]Fluoroacetyl-5-hydroxytryptamine)" J.Labelled Compds.Radiopharm.34. 741-746 (1994)
  • Description: 「研究成果報告書概要(欧文)」より