Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1088, USA.
J Nucl Med. 2013 May;54(5):770-5. doi: 10.2967/jnumed.112.112110. Epub 2013 Mar 27.
We have recently developed a cancer-specific therapy, photoimmunotherapy, which uses an antibody-IR700 (phototoxic phthalocyanine dye) conjugate to bind to the cell membrane and near-infrared light to induce immediate and highly specific tumor killing in vivo. For monitoring the acute cytotoxic effects of photoimmunotherapy before the tumor begins to shrink, we used (18)F-FDG PET before and after this intervention in mice.
Photoimmunotherapy was performed by binding panitumumab (anti-HER1)-IR700 to HER1-positive tumor cells (A431), followed by near-infrared light irradiation in vitro and in vivo. The uptake of (18)F-FDG in the tumor after photoimmunotherapy was evaluated in cellular uptake studies and PET imaging studies. Serial histologic analyses were conducted after photoimmunotherapy.
The in vitro cellular uptake of (18)F-FDG was reduced as the dose of light increased, and at high light dose (2 J/cm(2)) the uptake was reduced by more than 99% within 1 h after photoimmunotherapy. In vivo (18)F-FDG PET imaging showed that the accumulation of radioactivity in the treated tumors decreased 76% at 75 min after photoimmunotherapy and did not change for 24 h. In contrast, no significant changes were demonstrated in nontreated tumors. None of tumors changed size within 24 h after photoimmunotherapy, although diffuse necrosis was observed in photoimmunotherapy-treated tumors.
Immediate cytotoxic effects induced by photoimmunotherapy were clearly detected by decreased glucose uptake using (18)F-FDG PET even before changes in tumor size became evident. (18)F-FDG allows the clinical assessment of the therapeutic effects of photoimmunotherapy earlier than anatomic methods that rely on tumor size.
我们最近开发了一种癌症特异性疗法，即光免疫疗法，该疗法使用抗体-IR700（光毒性酞菁染料）缀合物与细胞膜结合，并利用近红外光在体内立即诱导高度特异性的肿瘤杀伤。为了在肿瘤开始缩小之前监测光免疫疗法的急性细胞毒性作用，我们在小鼠中在该干预前后使用（18）F-FDG PET。
光免疫疗法是通过将 panitumumab（抗 HER1）-IR700 与 HER1 阳性肿瘤细胞（A431）结合，然后在体外和体内进行近红外光照射来进行的。在光免疫疗法后，通过细胞摄取研究和 PET 成像研究评估肿瘤中（18）F-FDG 的摄取。在光免疫疗法后进行了连续的组织学分析。
随着光剂量的增加，（18）F-FDG 的体外细胞摄取减少，并且在高光剂量（2 J/cm（2））下，在光免疫疗法后 1 小时内摄取减少了 99％以上。体内（18）F-FDG PET 成像显示，在光免疫疗法后 75 分钟，处理过的肿瘤中放射性物质的积累减少了 76％，并且在 24 小时内没有变化。相比之下，未处理的肿瘤没有显示出明显的变化。尽管在光免疫疗法治疗的肿瘤中观察到弥漫性坏死，但在光免疫疗法后 24 小时内，没有一个肿瘤的大小发生变化。
使用（18）F-FDG PET 通过降低葡萄糖摄取，即使在肿瘤大小变化变得明显之前，也可以清楚地检测出光免疫疗法引起的即时细胞毒性作用。（18）F-FDG 允许临床评估光免疫疗法的治疗效果，比依赖肿瘤大小的解剖方法更早。
