Nuclear Medicine and Molecular Imaging

The Korean Society of Nuclear Medicine (대한핵의학회)
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Synthesis of (4-$[^{18}F]$Fluorophenyl)triphenylphosphonium as a Mitochondrial Voltage Sensor for PET

PET영상용 미토콘드리아 막전위 감지기 (4-$[^{18}F]$Fluorophenyl)triphenylphosphonium의 합성

  • Kim, Dong-Yeon (Department of Nuclear Medicine, Chonnam National University Medical School) ;
  • Yu, Kook-Hyun (Department of Chemistry, Dongguk University) ;
  • Bom, Hee-Seung (Department of Nuclear Medicine, Chonnam National University Medical School) ;
  • Min, Jung-Joon (Department of Nuclear Medicine, Chonnam National University Medical School)
  • 김동연 (전남대학교 의과대학 핵의학교실) ;
  • 유국현 (동국대학교 화학과) ;
  • 범희승 (전남대학교 의과대학 핵의학교실) ;
  • 민정준 (전남대학교 의과대학 핵의학교실)
  • Published : 2007.12.31
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Abstract

Purpose: Lipophilic cations including tetraphenylphosphonium (TPP) salts penetrate the hydrophobic barriers of the plasma and mitochondrial membranes, resulting in accumulation in mitochondria in response to the negative inner transmembrane potentials. The development of radiolabeled phosphonium cations as a noninvasive imaging agent may serve as a new molecular "voltage sensor" probe to investigate the role of mitochondria in the pathophysiology and diagnosis of cancer. Materials and Methods: We have synthesized a reference compound (4-fluorophenyl)triphenylphosphonium (TPP) and a labeled compound $[^{18}F]$TPP via two step nucleophilic substitution of no-carrier-added $[^{18}F]$fluoride with the precursor, 4-iodophenyltrimethylammonium iodide, in the presence of Kryptofix-2.2.2 and $K_2CO_3$. Result: The reference compound (4-fluorophenyl)triphenylphosphonium (TPP) was synthesized in 60% yield. The radiolabeled compound $[^{18}F]$TPP was synthesized in $10\sim15%$ yield. The radiochemical purity of the $[^{18}F]$TPP was $95.57{\pm}0.51%$ (n=11). Conclusion: $[^{18}F]$TPP was successfully synthesized that might have a potential to be utilized as a novel myocardial or cancer imaging agent for PET. However, it is required to improve the radiochemical yield to apply $[^{18}F]$TPP in preclinical or clinical researches.

목적: Tetraphenylphosphonium (TPP) salts를 비롯한 지용성 양이온들은 혈장 및 미토콘드리아막을 쉽게 통과할 수 있을 뿐 아니라 미토콘드리아 내의 음 전압에 이끌려 미토콘드리아의 내부에 직접적으로 섭취된다. 또한 tetraphenylphosphonium (TPP) salts는 암세포에 직접적으로 섭취될 뿐 아니라 미토콘드리아의 활동이 활발한 심근에서도 직접적 섭취가 일어나는 것으로 보고되어 있다. 따라서 이러한 특징을 가지는 tetraphenylphosphonium (TPP) salts에 $[^{18}F]$fluoride를 표지 할 수 있다면 암의 진단 및 미토콘드리아의 기능에 대해 연구 할 수 있는 새로운 분자 영상 추적자로써 사용할 수 있을 것이다. 대상 및 방법: 기준 물질인 (4-fluorophenyl)triphenylphosphonium (TPP)을 단일 반응으로 합성 하였으며, $[^{18}F]$이 표지된 TPP는 무담체$[^{18}F]$fluoride와 전구체인 4-iodophenyltrimethylammonium iodide를 이용하여 Kryptofix-2.2.2와 $K_2CO_3$존재 하에 두 단계의 반응으로 합성하였다. 결과: 기준물질인 (4-fluorophenyl) triphenylphosphonium (TPP)은 60%의 수율로 합성 되었으며, 표지 화합물인 $[^{18}F]$TPP의 방사 화학적 수율은 10-15%였다. 또한 radio TLC로 확인한 방사 화학적 순도는 $95.57{\pm}0.51%$ (n=11)이었다. 결론: 미토콘드리아의 막전위 차를 이용한 암 또는 심근 영상제제인 (4-$[^{18}F]$fluorophenyl) triphenylphosphonium의 합성에 성공하였다. 하지만 전임상, 임상에의 응용을 위해서는 방사화학적 수율을 더 개선시켜야 할 것이다.

Keywords

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