글로벌 연구동향
핵의학
- 2015년 08월호
Radiosynthesis and evaluation of 18F-labeled aliphatic phosphonium cations as a myocardial imaging agent for positron emission tomography.(전남의대/김동연,김현식,민정준*)
- 출처
- Nucl Med Commun.
- 등재일
- 2015 Jul
- 저널이슈번호
- 36(7):747-54.
- 내용
[Abstract]INTRODUCTION: Lipophilic cations such as phosphonium cations penetrate the hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in the mitochondria in response to negative inner-transmembrane potentials. The present study reports the radiosynthesis and evaluation of (18)F-labeled aliphatic triphenylphosphonium cations as a potential agent for myocardial imaging by using PET.
MATERIALS AND METHODS:
(7-[(18)F]fluoroheptyl)triphenylphosphonium salt ([(18)F]3) and (8-[(18)F]fluorooctyl)triphenylphosphonium salt ([(18)F]6) were radiolabeled by means of two-step nucleophilic substitution reactions. We measured the log P value of [(18)F]3 and [F]6 to assess the appropriate range of lipophilicity for their suitability as PET myocardial imaging agents. Normal rats were imaged with microPET after intravenous injection of 37 MBq of [(18)F]3 and [(18)F]6. To determine the pharmacokinetics, a region of interest was drawn around the heart, and time-activity curves of [(18)F]3 and [(18)F]6 were generated to obtain the counts per pixel per second.
RESULTS:
The radiolabeled compounds [(18)F]3 and [(18)F]6 were synthesized with 18-25% yield. The radiochemical purity was greater than 98% on the basis of the analytical high-performance liquid chromatography system, and the specific activity was greater than 160-170 Ci/mmol. The log P value of the tracers was 2.52 ± 0.01 ([(18)F]3) and 2.91 ± 0.02 ([(18)F]6). Myocardium-to-liver ratios of [(18)F]3 and [(18)F]6 were 2.59 and 1.07, respectively, 10 min after injection, whereas the myocardium-to-lung ratios were 5.57 and 3.35, respectively. In addition, [(18)F]3 and [(18)F]6 showed intense, homogenous uptake in the myocardium.
CONCLUSION: (18)F-labeled aliphatic phosphonium cations [(18)F]3 and [(18)F]6 might have potential as novel myocardial agents for PET and could prove useful in clinical cardiac PET/computed tomography applications.
[Author Information]
Kim DY1, Kim HS, Min JJ.
1Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
- 연구소개
- 심근허혈을 진단하는 PET 검사방법으로는 N-13 ammonia PET가 있는데 반감기가 10분 이내로 짧은 점 때문에 임상에서 광범위하게 이용되지 못하고 있다. 본 연구팀에서는 PET 심장영상의 활성화를 위하여 심근세포의 미토콘드리아에 섭취가 잘되는 phosphonium cation에 18F이 표지된 PET 영상제제를 개발하고 있는데, 본 연구에서는 18F이 표지된 aliphatic chain을 triphenylphosphonium과 결합시켜 소동물에서의 심근영상을 평가하였다. 특히 18F이 표지된 PET용 triphenylphosphonium cation 계열 심근영상제제의 선택적 심근 섭취가 log P 값에 의해 큰 영향을 받는 점을 보고하였고, 이러한 심근 선택적 log P 값의 범위를 기존보다 더 확대하였다는데 의의를 가지고 있다.
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