Automated radiosynthesis of the 18F-labeled BF2-chelated tetraaryl-azadipyrromethenes photosensitizer using isotopic exchange

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.

書誌情報

Nuclear Medicine and Biology

発行日 2022-06

出版者

Elsevier Ltd.

ISSN

収録物識別子タイプ

ISSN

収録物識別子

0969-8051

戻る

views

See details

	Views

Versions

Ver.1

2023-05-15 16:47:18.805901

Show All versions

Cite as

エクスポート

OAI-PMH

JPCOAR 2.0
JPCOAR 1.0
DublinCore
DDI

Other Formats

JSON
BIBTEX

インデックスリンク

インデックスツリー

アイテム