用于规划光动力治疗的光敏剂 ADPM06 的 18F 标记类似物的自动放射合成和体内评估,EJNMMI Radiopharmacy and Chemistry

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用于规划光动力治疗的光敏剂 ADPM06 的 18F 标记类似物的自动放射合成和体内评估
EJNMMI Radiopharmacy and Chemistry ( IF 4.4 ) Pub Date : 2023-07-17 , DOI: 10.1186/s41181-023-00199-y
Kazunori Kawamura ₁ , Tomoteru Yamasaki ₁ , Masayuki Fujinaga ₁ , Tomomi Kokufuta ₁ , Yiding Zhang ₁ , Wakana Mori ₁ , Yusuke Kurihara _{1,

2} , Masanao Ogawa _{1,

2} , Kaito Tsukagoe _{1,

2} , Nobuki Nengaki _{1,

2} , Ming-Rong Zhang ₁

Affiliation

BF2 螯合四芳基氮杂二吡咯甲烷家族被开发为用于光动力治疗的非卟啉光敏剂。在已开发的光敏剂中，ADPM06表现出优异的光化学和光物理性能。分子成像是光动力治疗规划和监测的有用工具。放射性标记光敏剂可以有效地解决光敏剂的生物分布问题，为光动力治疗规划提供有用的信息。为了评估ADPM06的生物分布并预测其在给药后立即进行光照射的光动力疗法中的药代动力学，我们合成了[18F]ADPM06并评估了其体内特性。使用ADPM06和氯化锡(IV)在室温下通过路易斯酸辅助同位素18F-19F交换10分钟自动合成[ 18 F]ADPM06。使用 0.4 μmol ADPM06 和 200 μmol 氯化锡 (IV) 进行放射性标记。放射合成时间约为60分钟，合成结束时放射化学纯度> 95%。合成开始时 [18F]F− 的衰变校正放射化学产率为 13 ± 2.7% (n = 5)。在雄性ddY小鼠的生物分布研究中，心脏、肺、肝脏、胰腺、脾脏、肾脏、小肠、肌肉和大脑的放射性水平在最初摄取后120分钟内逐渐下降。大腿骨的平均放射性水平是所有研究器官中最高的，并且在注射后 120 分钟内有所增加。与ADPM06共同注射后，雄性ddY小鼠血液和大脑中的放射性水平显着升高，而心脏、肺、肝脏、胰腺、肾脏、小肠、肌肉和大腿骨中的放射性水平没有受到影响。在雌性 BALB/c-nu/nu 小鼠注射后 30 分钟血浆代谢物分析中，与 [18F]ADPM06 相对应的放射性百分比为 76.3 ± 1.6% (n = 3)。在使用 MDA-MB-231-HTB-26 荷瘤小鼠（雌性 BALB/c-nu/nu）进行的正电子发射断层扫描研究中，放射性在骨中累积相对较高水平，在肿瘤中累积中等水平。注射后60分钟。我们使用自动18F标记合成仪合成了[18F]ADPM06，并使用[18F]ADPM06在小鼠体内的生物分布来评估ADPM06的初始摄取和药代动力学，以指导光照射的光动力治疗。

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Automated radiosynthesis and in vivo evaluation of 18F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy

A family of BF2-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 with light irradiation immediately after administration, we synthesized [18F]ADPM06 and evaluated its in vivo properties. [18F]ADPM06 was automatically synthesized by Lewis acid-assisted isotopic 18F-19F 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 [18F]F− at the start of synthesis was 13 ± 2.7% (n = 5). In the biodistribution study of male ddY mice, 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 thighbone 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 and brain significantly increased, whereas those in the heart, lung, liver, pancreas, kidney, small intestine, muscle, and thighbone of male ddY mice were not affected. In the metabolite analysis of the plasma at 30 min post-injection in female BALB/c-nu/nu mice, the percentage of radioactivity corresponding to [18F]ADPM06 was 76.3 ± 1.6% (n = 3). In a positron emission tomography study using MDA-MB-231-HTB-26 tumor-bearing mice (female BALB/c-nu/nu), radioactivity accumulated in the bone at a relatively high level and in the tumor at a moderate level for 60 min after injection. We synthesized [18F]ADPM06 using an automated 18F-labeling synthesizer and evaluated the initial uptake and pharmacokinetics of ADPM06 using biodistribution of [18F]ADPM06 in mice to guide photodynamic therapy with light irradiation.

更新日期：2023-07-18

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