CD146‐Targeted Multimodal Image‐Guided Photoimmunotherapy of Melanoma

Abstract

For melanoma resistant to molecularly targeted therapy and immunotherapy, new treatment strategies are urgently needed. A molecularly targeted theranostic pair may thus be of importance, where the diagnostic probe facilitates patient stratification and the therapeutic companion treats the selected cases. For this purpose, flow cytometry is used to assess the CD146 level in melanoma cells. Based on YY146, a CD146‐specific monoclonal antibody, an imaging probe 89 Zr‐Df‐YY146 is synthesized and its diagnostic performance is evaluated by positron emission tomography (PET) imaging. Furthermore, a photoimmunotherapy (PIT) agent IR700‐YY146 is developed and the therapeutic effect of IR700‐YY146 PIT is assessed comprehensively. CD146 is highly expressed in A375 and SK‐MEL‐5 cells. 89 Zr‐Df‐YY146 PET readily detects CD146‐positive A375 melanomas. Tumor accumulation of 89 Zr‐Df‐YY146 peaks at 72 h with an uptake value of 26.48 ± 3.28%ID g −1 , whereas the highest uptake of the nonspecific 89 Zr‐Df‐IgG is 4.80 ± 1.75%ID g −1 . More importantly, IR700‐YY146 PIT effectively inhibits the growth of A375 tumors, owing to production of reactive oxygen species, decreased glucose metabolism, and reduced expression of CD146. To conclude, 89 Zr‐Df‐YY146 and IR700‐YY146 are a promising theranostic pair with the former revealing CD146 expression in melanoma as a PET probe and the latter specifically treating CD146‐positive melanoma as an effective PIT agent.

Carcinoembryonic antigen-targeted photodynamic therapy in colorectal cancer models

“…The main advantage of tPDT over other adjuvant therapies is the ability to selectively apply therapy to local areas and tissues of interest, thereby minimizing side effects. When combined with NIR fluorescence or nuclear imaging, its potential for clinical use as theranostic approach is highlighted even further [26, 27].…”

Review and prospect of CD146 research

“…抗体, 可以识别人类10余种肿瘤. 蔡伟波等人制备了 YY146-核素 [228,236,291,373~375] 、YY146-纳米磁颗粒-荧光 素 [376] 、荧光素-YY146-核素 [219] 以及YY146-光敏 剂 [375] , 用于肿瘤可视化成像的应用研究. 这些抗体主 要集中在肿瘤成像分级评估以及术中导航, 包括神经 胶质瘤、胃癌、肺癌、肝癌、黑色素瘤、非小细胞 肺癌.…”

Near Infrared Light Triggered Photo/Immuno-Therapy Toward Cancers

“…An example is the use of Diiodo-substituted BODIPYs as a non-porphyrin photosensitizer for PDT improved the killing efficiency of melanoma B16F10 cells (Wang W. et al, 2016). Wei et al (2019) reported a type of PIT agent, IR700-YY146, achieved high therapeutic index for melanomas of relatively smaller volumes. However, the treatment efficacy for larger tumors was not ideal due to the penetration of light through skin and tissues into the large tumor.…”

“…However, the treatment efficacy for larger tumors was not ideal due to the penetration of light through skin and tissues into the large tumor. Repeated treatment and increased the energy transfer ratio of the PIT agents may be helpful to treat large and deep tumors (Mallidi et al, 2016;Wei et al, 2019).…”