量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Objectives:
A family of the BF2-chelated tetraaryl-azadipyrromethenes (ADPMs) was developed as a nonporphyrin photosensitizer (PS) for photodynamic therapy (PDT) [1]. Among ADPMs, ADPM06 displayed excellent photochemical and photophysical properties [1]. In addition, PDT using ADPM06 elicited impressive complete response rates in various tumor models when a short drug-light interval was applied [2]. Molecular imaging is a promising PDT planning and monitoring tool, and the PS biodistribution is a relevant issue for PDT planning that radiolabeled PSs may address efficiently. To evaluate efficiency for PDT using ADPM06 and also side effects of ADPM, we synthesized [18F]ADPM06 using an automated 18F-labeling synthesizer, and evaluated its in vivo properties.
Methods: [18F]ADPM06 was synthesized using an automated 18F-labeling synthesizer by Lewis acid-assisted isotopic 18F-19F exchange [3]. The [18F]F– was extracted from a Sep-Pak Accell Plus QMA Carbonate Plus Light cartridge with a mixture of tetrabutylanmmonium bicarbonate aqueous solution and acetonitrile. The solution was concentrated by evaporation at 100 °C for 10 min under nitrogen gas flow. After the reaction vessel was cooled, the mixture of ADPM06 in acetonitrile and tin(IV) chloride (SnCl4) solution was added to the reaction vessel, and then was agitated using magnetic stirrer at room temperature for 10 min. After the reaction, the mixture was diluted with water for injection, and transferred to the injector for semi-preparative radio-HPLC. The HPLC fractions were collected in a flask, to which Tween 80 in ethanol was added prior to radiosynthesis. The solution was subsequently evaporated to dryness and the residue was dissolved in physiological saline. The product was analyzed by HPLC with radioactivity and UV-VIS detection. The in vivo biodistribution study was performed using mice.
Results:
To radio-synthesize efficiently [18F]ADPM06, we performed semi-automated radiosynthesis. By increasing the concentration of SnCl4 from 100 to 400 μmol, the radiochemical conversion (RCC) of [18F]ADPM06 from [18F]TBAF was increased until 60%. Also, the RCC using 0.8 μmol of ADPM06 was 1.2-fold higher than that using 0.4 μmol of ADPM06. In the radiosynthesis using an automated 18F-labeling synthesizer, we successfully synthesized [18F]ADPM06 for in vivo applications. The radiochemical yield (RCY) from [18F]F- was 13 ± 2.7 % (n = 5; 0.4 μmol of ADPM06, 200 μmol of SnCl4) at the end of irradiation. The radiosynthesis time was within 60 min, and radiochemical purity remained >95% after maintaining it for 1 hour after the end of synthesis. In the biodistribution study within 120 min after the injection, radioactivity levels in heart, lung, liver, pancreas, spleen, kidney, small intestine, muscle, and brain gradually decreased after initial uptake.
Conclusions: We enabled to synthesize [18F]ADPM06 using an automated 18F-labeling synthesizer, and to evaluate biodistribution of [18F]ADPM06 in mice.
Automated radiosynthesis of the 18F-labeled BF2-chelated tetraaryl-azadipyrromethenes photosensitizer using isotopic exchange
