Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) is a molecularly targeted cancer therapy that employs antibody–photoabsorber conjugates (APCs) comprising the photosensitizer IRDye700DX (IR700) and tumor-specific antibodies. Following near-infrared (NIR) light irradiation, IR700 undergoes structural modification, inducing selective and rapid necrotic cell death. In mouse tumor models, we observed that IR700 fluorescence decreased during irradiation but recovered immediately afterward. This study aimed to characterize this novel phenomenon, named “early fluorescence recovery,” and explore its therapeutic implications.Methods: Cetuximab-IR700 (Cet-IR700) was synthesized and administered to A431 and FaDu-Luc2 xenograft female BALB/c-nu/nu mouse models. In vivo fluorescence imaging was conducted using LIGHTVISION during and after NIR irradiation (690 nm, 50 J/cm2). Reactive oxygen species involvement was examined via intraperitoneal administration of L-sodium ascorbate. Tumor blood flow changes were assessed via indocyanine green (ICG) imaging, and therapeutic efficacy was compared between single and divided irradiation protocols.Results: Tumor fluorescence markedly decreased during NIR-PIT but rapidly recovered within 10 min after irradiation. This recovery was significantly inhibited by L-sodium ascorbate (p< 0.01) and accompanied by increased ICG fluorescence (p< 0.01), suggesting enhanced tumor perfusion. Divided irradiation performed after fluorescence recovery tended to yield greater tumor suppression than did single irradiation, although the difference was not statistically significant.Conclusions: Early fluorescence recovery after NIR-PIT reflects transient reactivation of photoactive APCs through oxygen-dependent molecular and vascular mechanisms. Exploiting this brief recovery window with divided irradiation may improve therapeutic efficacy and guide optimization of NIR-PIT protocols.
**背景/目的：** 近红外光免疫疗法是一种分子靶向癌症疗法，其使用由光敏剂IRDye700DX和肿瘤特异性抗体构成的抗体-光吸收偶联物。在近红外光照射后，IR700发生结构修饰，诱导选择性、快速的坏死性细胞死亡。在小鼠肿瘤模型中，我们观察到IR700荧光在照射期间减弱，但照射后立即恢复。本研究旨在描述这一名为"早期荧光恢复"的新现象，并探讨其治疗意义。 **方法：** 合成了西妥昔单抗-IR700，并将其施用于A431和FaDu-Luc2异种移植雌性BALB/c-nu/nu小鼠模型。使用LIGHTVISION系统在NIR照射期间和照射后进行体内荧光成像。通过腹腔注射L-抗坏血酸钠来检测活性氧的参与。通过吲哚菁绿成像评估肿瘤血流变化，并比较单次与分次照射方案的治疗效果。 **结果：** 肿瘤荧光在NIR-PIT期间显著减弱，但在照射后10分钟内迅速恢复。L-抗坏血酸钠显著抑制了这种恢复，并伴有ICG荧光增强，提示肿瘤灌注增加。在荧光恢复后进行的分次照射方案，其肿瘤抑制效果倾向于优于单次照射，尽管差异无统计学显著性。 **结论：** NIR-PIT后的早期荧光恢复反映了光活性APC通过氧依赖的分子和血管机制发生短暂再激活。利用这一短暂的恢复窗口进行分次照射，可能提高治疗效果，并指导NIR-PIT方案的优化。
肿瘤(癌症)患者之家