Jin Cheng S, Overchuk Marta, Cui Liyang, Wilson Brian C, Bristow Robert G, Chen Juan, Zheng Gang
Princess Margaret Cancer Center, UHN, Toronto, Canada.
Faculty of Pharmacy, Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada.
Prostate. 2016 Sep;76(13):1169-81. doi: 10.1002/pros.23203. Epub 2016 May 16.
The Magnetic Resonance Imaging (MRI)-guided focal laser therapy has shown early promise in Phase 1 trial treating low/intermediate-risk localized prostate cancer (PCa), but the lack of tumor selectivity and low efficiency of heat generation remain as drawbacks of agent-free laser therapy. Intrinsic multifunctional porphyrin-nanoparticles (porphysomes) have been exploited to treat localized PCa by MRI-guided focal photothermal therapy (PTT) with significantly improved efficiency and tumor selectivity over prior methods of PTT, providing an effective and safe alternative to active surveillance or radical therapy.
The tumor accumulation of porphysomes chelated with copper-64 was determined and compared with the clinic standard (18) F-FDG in an orthotropic PCa mouse model by positron emission tomography (PET) imaging, providing quantitative assessment for PTT dosimetry. The PTT was conducted with MRI-guided light delivery and monitored by MR thermometry, mimicking the clinical protocol. The efficacy of treatment and adverse effects to surround tissues were evaluated by histology analysis and tumor growth in survival study via MRI.
Porphysomes showed superior tumor-to-prostate selectivity over (18) F-FDG (6:1 vs. 0.36:1). MR thermometry detected tumor temperature increased to ≥55°C within 2 min (671 nm at 500 mW), but minimal increase in surrounding tissues. Porphysome enabled effective PTT eradication of tumor without damaging adjacent organs in orthotropic PCa mouse model.
Porphysome-enabled MRI-guided focal PTT could be an effective and safe approach to treat PCa at low risk of progression, thus addressing the significant unmet clinical needs and benefiting an ever-growing number of patients who may be over-treated and risk unnecessary side effects from radical therapies. Prostate 76:1169-1181, 2016. © 2016 Wiley Periodicals, Inc.
磁共振成像(MRI)引导下的聚焦激光治疗在治疗低/中危局限性前列腺癌(PCa)的1期试验中已显示出早期前景,但缺乏肿瘤选择性和产热效率低仍是无介质激光治疗的缺点。内在多功能卟啉纳米颗粒(卟啉体)已被用于通过MRI引导的聚焦光热疗法(PTT)治疗局限性PCa,与先前的PTT方法相比,其效率和肿瘤选择性显著提高,为主动监测或根治性治疗提供了一种有效且安全的替代方案。
在原位PCa小鼠模型中,通过正电子发射断层扫描(PET)成像确定与铜-64螯合的卟啉体的肿瘤蓄积,并与临床标准(18)F-FDG进行比较,为PTT剂量测定提供定量评估。PTT采用MRI引导的光传输进行,并通过磁共振测温进行监测,模拟临床方案。通过组织学分析和MRI生存研究中的肿瘤生长评估治疗效果和对周围组织的不良反应。
卟啉体显示出比(18)F-FDG更高的肿瘤与前列腺选择性(6:1对0.36:1)。磁共振测温检测到肿瘤温度在2分钟内升至≥55°C(500 mW时671 nm),但周围组织温度升高极小。在原位PCa小鼠模型中,卟啉体能够有效进行PTT根除肿瘤而不损伤邻近器官。
基于卟啉体的MRI引导聚焦PTT可能是一种治疗进展风险低的PCa的有效且安全的方法,从而满足重大未满足的临床需求,并使越来越多可能接受过度治疗且面临根治性治疗不必要副作用风险的患者受益。《前列腺》76:1169 - 1181,2016年。©2016威利期刊公司。