Photodynamic therapy of established prostatic adenocarcinoma with TOOKAD: A biphasic apparent diffusion coefficient change as potential early MRI response marker
Photodynamic therapy of established prostatic adenocarcinoma with TOOKAD: A biphasic apparent diffusion coefficient change as potential early MRI response marker
复制标题
DOI：
10.1593/neo.03352
复制
发表时间：
2004-05-01
期刊：
影响因子：
4.8
通讯作者：
Salomon, Y
中科院分区：
文献类型：
--
作者：
Plaks, V;Koudinova, N;Salomon, Y
本研究的目的是检验弥散加权磁共振成像 (DW-MRI) 的用途，以评估基于 Pd 细菌脱镁叶绿酸 (TOOKAD) 的光动力疗法 (PDT) 引起的光损伤的早期进展。 TOOKAD 是我们实验室开发的用于实体瘤 PDT 的新型第二代光敏剂，目前正在进行前列腺癌 (PC) 治疗的临床试验。使用裸鼠皮下人前列腺腺癌WISH-PC14异种移植物作为模型，在PDT后的前24小时内观察到表观扩散系数（ADC）独特的双相变化，ADC先下降，随后上升。使用 DW-MRI，这种现象能够在治疗后 7 小时内检测到肿瘤对 PDT 的成功反应。该过程通过直接组织学和免疫组织化学检查以及治疗后 7 小时已显着下降的血清前列腺特异性抗原 (PSA) 水平的评估得到验证。多细胞球体的体外研究证实了 PDT 诱导的 ADC 下降，表明脂质过氧化 (LPO) 显着导致 PDT 后观察到的 ADC 下降。这些结果表明，基于 TOOKAD 的 PDT 成功根除前列腺腺癌异种移植物，并表明 DW-MRI 可用于检测临床环境中的早期肿瘤反应和治疗结果。
The goal of this study was to examine the use of diffusion-weighted magnetic resonance imaging (DW-MRI) for the assessment of early progression of photodamage induced by Pd-bacteriopheophorblde (TOOKAD)-based photodynamic therapy (PDT). TOOKAD is a novel second-generation photosensitizer for PDT of solid tumors developed in our laboratory and presently under clinical trials for prostate cancer (PC) therapy. Using the subcutaneous human prostate adenocarcinoma WISH-PC14 xenografts in nude mice as a model, a unique biphasic change in the apparent diffusion coefficient (ADC) was observed within the first 24 hours post-PDT, with initial decrease followed by an increase in ADC. Using DW-MRI, this phenomenon enables the detection of successful tumor response to PDT within 7 hours posttreatment. This process was validated by direct, histological, and immunohistochemical examinations and also by evaluation of serum prostate-specific antigen (PSA) levels that decreased significantly already 7 hours posttreatment. In vitro studies of multicellular cell spheroids confirmed a PDT-induced decrease in ADC, suggesting that lipid peroxidation (LPO) significantly contributes to ADC decline observed after PDT. These results demonstrate that TOOKAD-based PDT successfully eradicates prostate adenocarcinoma xenografts and suggests DW-MRI to be useful for the detection of early tumor response and treatment outcome in the clinical setting.