Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment.
Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment.
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DOI：
10.1038/sj.bjc.6605247
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发表时间：
2009-11-03
影响因子：
8.8
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中科院分区：
文献类型：
--
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光动力疗法（PDT）是一种治疗包括癌症在内的一系列疾病的方法。BF2螯合的四芳基氮杂二吡咯亚甲基（ADPMs）是一类新兴的非卟啉光动力治疗剂，其先前显示出优异的光化学和光物理性质用于治疗应用。在此，已完成了先导药物ADMP 06的体内疗效和作用机制研究。采用多模态成像方法评估治疗效果，并探索ADPM06介导的PDT的作用机制。在给予2 mg kg−1 ADPM 06后立即用150 J cm−2光照射，71%的乳腺肿瘤动物实现了肿瘤消融。ADPM 06的固有荧光用于监测器官生物分布模式，24小时内所有器官中的荧光均达到基线水平。使用动态正电子发射断层扫描和磁共振成像技术进行了作用机制研究，当两者结合在一起时，表明治疗后随着时间的推移，肿瘤血管灌注减少，肿瘤代谢随之减少。令人鼓舞的治疗反应在体内和血管靶向的作用机制继续表明这种新的光敏剂类的治疗效益。
Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF2-chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06. A multi-modality imaging approach was employed to assess efficacy of treatment, as well as probe the mechanism of action of ADPM06-mediated PDT. Tumour ablation in 71% of animals bearing mammary tumours was achieved after delivery of 2 mg kg−1 of ADPM06 followed immediately by light irradiation with 150 J cm−2. The inherent fluorescence of ADPM06 was utilised to monitor organ biodistribution patterns, with fluorescence reaching baseline levels in all organs within 24 h. Mechanism of action studies were carried out using dynamic positron emission tomography and magnetic resonance imaging techniques, which, when taken together, indicated a decrease in tumour vascular perfusion and concomitant reduction in tumour metabolism over time after treatment. The encouraging treatment responses in vivo and vascular-targeting mechanism of action continue to indicate therapeutic benefit for this new class of photosensitiser.
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