Department of Radiology, Emory Center for Systems Imaging, Emory University, Atlanta, Georgia 30329, USA.
J Nucl Med. 2010 Jan;51(1):130-8. doi: 10.2967/jnumed.109.067579. Epub 2009 Dec 15.
Photodynamic therapy (PDT) is a relatively new therapy that has shown promise for treating various cancers in both preclinical and clinical studies. The present study evaluated the potential use of PET with radiolabeled choline to monitor early tumor response to PDT in animal models.
Two human prostate cancer models (PC-3 and CWR22) were studied in athymic nude mice. A second-generation photosensitizer, phthalocyanine 4 (Pc 4), was delivered to each animal by a tail vein injection 48 h before laser illumination. Small-animal PET images with (11)C-choline were acquired before PDT and at 1, 24, and 48 h after PDT. Time-activity curves of (11)C-choline uptake were analyzed before and after PDT. The percentage of the injected dose per gram of tissue was quantified for both treated and control tumors at each time point. In addition, Pc 4-PDT was performed in cell cultures. Cell viability and (11)C-choline uptake in PDT-treated and control cells were measured.
For treated tumors, normalized (11)C-choline uptake decreased significantly 24 and 48 h after PDT, compared with the same tumors before PDT (P < 0.001). For the control tumors, normalized (11)C-choline uptake increased significantly. For mice with CWR22 tumors, the prostate-specific antigen level decreased 24 and 48 h after PDT. Pc 4-PDT in cell culture showed that the treated tumor cells, compared with the control cells, had less than 50% (11)C-choline activity at 5, 30, and 45 min after PDT, whereas the cell viability test showed that the treated cells were viable longer than 7 h after PDT.
PET with (11)C-choline is sensitive for detecting early changes associated with Pc 4-PDT in mouse models of human prostate cancer. Choline PET has the potential to determine whether a PDT-treated tumor responds to treatment within 48 h after therapy.
光动力疗法（PDT）是一种相对较新的疗法，已在临床前和临床研究中显示出治疗各种癌症的潜力。本研究评估了用放射性标记胆碱的 PET 监测动物模型中 PDT 早期肿瘤反应的潜力。
在裸鼠中研究了两种人前列腺癌模型（PC-3 和 CWR22）。第二代光敏剂酞菁 4（Pc4）在激光照射前 48 小时通过尾静脉注射递送至每个动物。在 PDT 前后采集小动物（11）C-胆碱 PET 图像。在 PDT 前后分析（11）C-胆碱摄取的时间-活性曲线。在每个时间点都对处理和对照肿瘤的组织每克注射剂量的百分比进行量化。此外，在细胞培养物中进行了 Pc4-PDT。测量 PDT 处理和对照细胞中的细胞活力和（11）C-胆碱摄取。
对于处理过的肿瘤，与 PDT 前相同的肿瘤相比，24 和 48 小时后归一化（11）C-胆碱摄取显着降低（P <0.001）。对于对照肿瘤，归一化（11）C-胆碱摄取显着增加。对于患有 CWR22 肿瘤的小鼠，前列腺特异性抗原水平在 PDT 后 24 和 48 小时下降。细胞培养中的 Pc4-PDT 显示，与对照细胞相比，处理过的肿瘤细胞在 PDT 后 5、30 和 45 分钟的（11）C-胆碱活性低于 50％，而细胞活力测试表明处理过的细胞在 PDT 后 7 小时以上仍保持活力。
（11）C-胆碱 PET 对检测人类前列腺癌小鼠模型中与 Pc4-PDT 相关的早期变化敏感。胆碱 PET 有可能在治疗后 48 小时内确定 PDT 治疗的肿瘤是否对治疗有反应。
