Nuclear Medicine and Molecular Imaging

  • 제40권4호
  • /
  • Pages.228-232
  • /
  • 2006
  • /
  • 1869-3474(pISSN)
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  • 1869-3482(eISSN)
대한핵의학회 (The Korean Society of Nuclear Medicine)
권호 표지

친전자성 치환반응을 위한 $[^{18}F]F_2$ Gas의 생산 연구

Production of $[^{18}F]F_2$ Gas for Electrophilic Substitution Reaction

  • 문병석 (원자력의학원 RI 및 방사성의약품개발실) ;
  • 김재홍 (원자력의학원 RI 및 방사성의약품개발실) ;
  • 이교철 (원자력의학원 RI 및 방사성의약품개발실) ;
  • 안광일 (원자력의학원 RI 및 방사성의약품개발실) ;
  • 천기정 (원자력의학원 RI 및 방사성의약품개발실) ;
  • 전권수 (원자력의학원 RI 및 방사성의약품개발실)
  • Moon, Byung-Seok (Laboratory of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences(KIRAMS)) ;
  • Kim, Jae-Hong (Laboratory of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences(KIRAMS)) ;
  • Lee, Kyo-Chul (Laboratory of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences(KIRAMS)) ;
  • An, Gwang-Il (Laboratory of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences(KIRAMS)) ;
  • Cheon, Gi-Jeong (Laboratory of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences(KIRAMS)) ;
  • Chun, Kwon-Soo (Laboratory of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences(KIRAMS))
  • 발행 : 2006.08.31
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초록

목적 : $[^{18}F]F_2\;(T_{1/2}=110\;min)$ 기체를 이용하여 친전자성 치환반응으로 방사성동위원소 $^{18}F$을 표지하는 방법은 새로운 앙전자방출단층촬영용 방사성의약품 개발 분야에서 유용하게 이용되고 있다. 그림에도 불구하고 $[^{18}F]F_2$를 높은 생산수율과 비방사능으로 생산하기 위한 표적 개발 연구는 아직도 진행 중에 있다. 본 연구에서는 친핵성 치환반응으로 $^{18}F$을 도입하기 어려운 방사성의약품에 친전자성 치환반응으로 방사성동위원소를 도입할 수 있는 $[^{18}F]F_2$ 가스의 효율적인 생산에 관해 연구하였다. 대상 및 방법: 표적은 원추형 모양의 알루미늄 재질로 제작하였다. $[^{18}F]F_2$ 생산을 위한 핵반응으로 $^{18}O(p,n)^{18}F$를 사용하였으며, two-step 빔 조사방법을 이용하였다. 첫 번째 조사는 농축 $[^{18}O]O_2$가스를 표적에 충진한 후 빔 조사하여 $^{18}O(p,n)^{18}F$ 핵반응을 일으킴으로써 $^{18}F$를 생산한다. 생산된 $^{18}F$은 표적 챔버 기벽에 흡착된다. $[^{18}O]O_2$은 재사용을 위하여 냉각포획법으로 회수하였으며, $^{18}F$를 회수하기 위해 $[^{19}F]F_2/Ar$ 가스를 충진한 후, 두 번째 빔을 조사하여 방사성불소를 회수하는 방법으로 구성된다. 본 연구에서는 최적의 방사성불소 생산 조건을 찾기 위해 빔 조사 시간, 빔 전류 세기 농축 $[^{18}O]O_2$ 충진 압력 등의 변화에 따라 생산량을 평가하였다. 결과: 빔 조사 시간, 빔 전류, 농축 $[^{18}O]O_2$ 충진 압력 등의 조건을 변화시키면서 생산량을 평가한 결과 최적의 빔 조사 조건은 다음과 같다. 첫 번째 조사: 농축 $[^{18}O]O_2$을 약 15.0 bar충진, 13.2 MeV, 30 ${\mu}A$로 60-90분 조사; 두 번째 조사: 1% $[^{19}F]F_2/Ar$혼합가스 12.0 bar 충진, 13.2 MeV, 30 ${\mu}A$로 20-30분 조사 후 아르곤 가스로 회수하였을 때 EOB(end of bombardment) 기준으로 약 $34{\pm}6.0$ GBq(n>10)의 $[^{18}F]F_2$를 얻었다. 결론: $^{18}O(p,n)^{18}F$ 핵반응을 이용하여 친전자성 방사성동위원소 $[^{18}F]F_2$를 생산하였다. 표적 챔버는 알루미늄으로 제작하였으며 본 연구에서 연구된 $[^{18}F]F_2$가스는 친핵성 치환반응으로 방사성동위원소를 도입하기 어려운 다양한 방사성의 약품개발에 유용하게 이용될 수 있을 것이다.

Purpose: electrophilic $^{18}F(T_{1/2}=110\;min)$ radionuclide in the form of $[^{18}F]F_2$ gas is of great significance for labeling radiopharmaceuticals for positron omission tomography (PET). However, its production In high yield and with high specific radioactivity is still a challenge to overcome several problems on targetry. The aim of the present study was to develop a method suitable for the routine production of $[^{18}F]F_2$ for the electrophilic substitution reaction. Materials and Methods: The target was designed water-cooled aluminum target chamber system with a conical bore shape. Production of the elemental fluorine was carried out via the $^{18}O(p,n)^{18}F$ reaction using a two-step irradiation protocol. In the first irradiation, the target filled with highly enriched $^{18}O_2$ was irradiated with protons for $^{18}F$ production, which were adsorbed on the inner surface of target body. In the second irradiation, the mixed gas ($1%[^{19}F]F_2/Ar$) was leaded into the target chamber, fellowing a short irradiation of proton for isotopic exchange between the carrier-fluorine and the radiofluorine absorbed in the target chamber. Optimization of production was performed as the function of irradiation time, the beam current and $^{18}O_2$ loading pressure. Results: Production runs was performed under the following optimum conditions: The 1st irradiation for the nuclear reaction (15.0 bar of 97% enriched $^{18}O_2$, 13.2 MeV protons, 30 ${\mu}A$, 60-90 min irradiation), the recovery of enriched oxygen via cryogenic pumping; The 2nd irradiation for the recovery of absorbed radiofluorine (12.0 bar of 1% $[^{19}F]fluorine/argon$ gas, 13.2 MeV protons, 30 ${\mu}A$, 20-30 min irradiation) the recovery of $[^{18}F]fluorine$ for synthesis. The yield of $[^{18}F]fluorine$ at EOB (end of bombardment) was achieved around $34{\pm}6.0$ GBq (n>10). Conclusion: The production of $^{18}F$ electrophilic agent via $^{18}O(p,n)^{18}F$ reaction was much under investigation. Especially, an aluminum gas target was very advantageous for routine production of $[^{18}F]fluorine$. These results suggest the possibility to use $[^{18}F]F_2$ gas as a electrophilic substitution agent.

키워드

참고문헌

  1. Guillaume M, Luxen A, Neveling B, Argentini M, Clark JC, Pike VW. Recommendations for fluorine-18 production. Appl Radiat Isot 1991;42:749-62 https://doi.org/10.1016/0883-2889(91)90179-5
  2. Luxen A, Perlmutter M, Bida GT, Van Moffaert G, Cook JS, Satyamurthy N, et al. Remote, semiautomated production of 6-[$^{18}F]fluoro-L-dopa for human studies with PET. Appl Radiat Isot 1990;41:275-81 https://doi.org/10.1016/0883-2889(90)90191-I
  3. Namavari M, Bishop A, Satyamurthy N, Bida G, Barrio JR. Regioselective radiofluorodestannylation with [$^{18}F]F2 and $[^{18}]CH_3COOF$; A high yield synthesis of 6-[$^{18}F]fluoro-L-dopa. Appl Radiat Isot 1992;43:989-96 https://doi.org/10.1016/0883-2889(92)90217-3
  4. Namavari M, Satyamurthy N, Phelps ME, Barrio JR. Synthesis of 6-[$^{18}F]fluoro-L-m-tyrosines via regioselective radiofluorodestannylation. Appl Radiat Isot 1993;44:527-36 https://doi.org/10.1016/0969-8043(93)90165-7
  5. Perlmutter MM, Satyamurthy N, Luxen A, Phelps ME, Barrio JR. Synthesis of 4-[$^{18}F]Fluoro-L-m-tyrosine: A model analog for the in-vivo assessment of central dopaminergic function. Appl Radiat Isot 1990;41:801-7 https://doi.org/10.1016/0883-2889(90)90056-M
  6. Imahori Y, Ueda S, Ohmori Y, Kusuki T, Ono K, Fujii R, et al. Fluorine-18-labeled fluoroboronophenylalanine PET in patients with Glioma. J Nucl Med 1998;39:325-33
  7. Bida GT, Hendry GO, Bishop AJ, Satyamurthy N. [18F]F2 production via low energy proton irradiation of $[^{18}O]O_2\;plus\;F_2$. Proc. IVth Int. Workshop on Targetry and Target Chemistry, Paul Scherrer Institut, September 1992;p130
  8. Wieland BW, Bida GT, Padgett HC, Hendry GO. Current status of CTI target systems for the production of PET radiochemicals. Proc. 3rd Workshop on Targetry, Vancouver, Canada. 1989;p34
  9. Casella V, Ido T, Wolf AP, Fowler JS, MacGregor RR, Ruth TJ. Anhydrous $^{18}F labelled elemental fluorine for radiopharmaceutical preparation. J Nucl Med 1980;21:750-7
  10. Ruth TJ, Wolf AP. Absolute cross sections for the production of $^{18}F via the $^{18}O(p,n)^{18}F$ reaction. Radiochemica Acta 1979;26:21-4
  11. Williams CF, Boujot JP, Picard J. Tables of range and stopping power of chemical elements for charged particles of energy 0.5 to 500 MeV. Rapport CAE-R 1966;3024
  12. Ziegler JF, Biersack JP, Littma가 U. The stopping and range of ions in solids, Pergaman Press, New York 1985
  13. Chirakal R, Adams RM, Firnau G, Schrobilgen GJ, Coates G, Garnett ES. Electrophilic $^{18}F from a Siemens 11 MeV proton-only cyclotron. Nucl Med Biol 1995;22:111-6 https://doi.org/10.1016/0969-8051(94)E0064-P