MR imaging biomarkers for evaluating therapeutic effects shortly after near infrared photoimmunotherapy.
MR imaging biomarkers for evaluating therapeutic effects shortly after near infrared photoimmunotherapy.
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DOI：
10.18632/oncotarget.7357
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发表时间：
2016-03-29
期刊：
影响因子：
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通讯作者：
Kobayashi H
中科院分区：
文献类型：
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作者：
Nakamura Y;Bernardo M;Nagaya T;Sato K;Harada T;Choyke PL;Kobayashi H
近红外光免疫疗法（NIR-PIT）是一种新的癌症治疗方法，结合了针对肿瘤的抗体的特异性和近红外光照射后光子吸收剂诱导的毒性。本研究的目的是确定 MR 成像是否可以在 NIR-PIT 几个小时内检测到肿瘤 MR 特性的变化。将 A431 细胞皮下注射到 12 只小鼠的左右背部。六天后，给小鼠注射了与帕尼单抗（一种针对表皮生长因子受体的抗体）结合的光子吸收剂 IR700。一天后，仅右侧肿瘤暴露于近红外光（已治疗的肿瘤）。在 NIR-PIT 前 1 天和 NIR-PIT 后 1-2 小时进行 MRI，对六只小鼠使用钆磷维特，对另外六只小鼠使用钆喷酸二葡胺。使用双边配对 t 检验比较 NIR-PIT 前后的 T2 弛豫时间、以下 b 值组合的表观扩散系数 (ADC)：0-1000、200-1000 和 500-1000 s/mm2 以及增强指数。对于治疗的肿瘤，NIR-PIT 后 T2 弛豫时间增加 (p < 0.01)，并且 NIR-PIT 后所有三个 ADC 值均下降 (p < 0.01)。此外，NIR-PIT 后使用 gadofosveset 的增强曲线下面积 (AUC) 有所增加 (p = 0.02)。总之，使用 gadofosveset 治疗肿瘤后 2 小时内即可观察到 T2 延长、ADC 降低和增强增强。因此，MRI 可以成为检测 NIR-PIT 后早期治疗变化的有用成像生物标志物。
Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photon absorbers after irradiation with NIR light. The purpose of this study was to determine if MR imaging can detect changes in the MR properties of tumor within several hours of NIR-PIT. A431 cells were injected subcutaneously in the right and left dorsi of 12 mice. Six days later, the mice were injected with a photon absorber, IR700, conjugated to panitumumab, an antibody targeting epidermal growth factor receptor. One day later, only right sided tumor was exposed to NIR light (treated tumor). MRI was performed 1 day before and 1-2 hours after NIR-PIT using gadofosveset for six mice and gadopentetate dimeglumine for another six mice. T2 relaxation times, the apparent diffusion coefficient (ADC) for the following combinations of b-values: 0-1000, 200-1000 and 500-1000 s/mm2 and enhancement indices were compared before and after NIR-PIT using a two-sided paired t-test. For treated tumors, T2 relaxation time increased after NIR-PIT (p < 0.01) and all three ADC values decreased after NIR-PIT (p < 0.01). Moreover, the enhancement area under the curve (AUC) using gadofosveset increased after NIR-PIT (p = 0.02). In conclusion, prolongation of T2, reductions in ADC and increased enhancement using gadofosveset are seen within 2 hours of NIR-PIT treatment of tumors. Thus, MRI can be a useful imaging biomarker for detecting early therapeutic changes after NIR-PIT.