Automated radiosynthesis and in vivo evaluation of [18F]ADPM06 as a photosensitizer for photodynamic therapy

Abstract Background A family of BF 2 -chelated tetraaryl-azadipyrromethenes was developed as non-porphyrin photosensitizers for photodynamic therapy. Among the developed photosensitizers, ADPM06 exhibited excellent photochemical and photophysical properties. Molecular imaging is a useful tool for photodynamic therapy planning and monitoring. Radiolabeled photosensitizers can efficiently address photosensitizer biodistribution, providing helpful information for photodynamic therapy planning. To evaluate the biodistribution of ADPM06 and predict its pharmacokinetics on photodynamic therapy, we synthesized [ 18 F]ADPM06 and evaluated its in vivo properties. Results [ 18 F]ADPM06 was automatically synthesized by Lewis acid-assisted isotopic 18 F- 19 F exchange using ADPM06 and tin (IV) chloride at room temperature for 10 min. Radiolabeling was carried out using 0.4 µmol of ADPM06 and 200 µmol of tin (IV) chloride. The radiosynthesis time was approximately 60 min, and the radiochemical purity was > 95% at the end of the synthesis. The decay-corrected radiochemical yield from [ 18 F]F - at the end of irradiation was 13 ± 2.7% ( n = 5). In the biodistribution study, radioactivity levels in the heart, lungs, liver, pancreas, spleen, kidney, small intestine, muscle, and brain gradually decreased over 120 min after the initial uptake. The mean radioactivity level in the bone was the highest among all organs investigated and increased for 120 min after injection. Upon co-injection with ADPM06, the radioactivity levels in the blood, heart, and brain significantly increased, whereas those in the lung, liver, pancreas, kidney, small intestine, muscle, and bone were not affected. In the metabolite study of the plasma in mice, the percentage of radioactivity corresponding to [ 18 F]ADPM06 was 76.3 ± 1.6% ( n = 3). In a positron emission tomography study using MDA-MB-231-HTB-26 tumor-bearing mice, radioactivity accumulated in the bone at a relatively high level and in the tumor at a moderate level for 60 min after injection. Conclusions We synthesized [ 18 F]ADPM06 using an automated 18 F-labeling synthesizer and evaluated the biodistribution of [ 18 F]ADPM06 in mice, which may be useful for predicting the pharmacokinetics of ADPM06 in photodynamic therapy.