Department of Chemistry, Hunter College, City University of New York, New York, NY 10021, USA.
Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY 10016, USA.
Molecules. 2020 May 15;25(10):2315. doi: 10.3390/molecules25102315.
High expression levels of the tumor-associated antigen MUC1 have been correlated with tumor aggressiveness, poor response to therapy, and poor survival in several tumor types, including breast, pancreatic, and epithelial ovarian cancer. Herein, we report the synthesis, characterization, and in vivo evaluation of a novel radioimmunoconjugate for the immuno-positron emission tomography (immunoPET) imaging of MUC1 expression based on the AR20.5 antibody. To this end, we modified AR20.5 with the chelator desferrioxamine (DFO) and labeled it with the positron-emitting radiometal zirconium-89 (t ~3.3 d) to produce [Zr]Zr-DFO-AR20.5. In subsequent in vivo experiments in athymic nude mice bearing subcutaneous MUC1-expressing ovarian cancer xenografts, [Zr]Zr-DFO-AR20.5 clearly delineated tumor tissue, producing a tumoral activity concentration of 19.1 ± 6.4 percent injected dose per gram (%ID/g) at 120 h post-injection and a tumor-to-muscle activity concentration ratio of 42.4 ± 10.6 at the same time point. Additional PET imaging experiments in mice bearing orthotopic MUC1-expressing ovarian cancer xenografts likewise demonstrated that [Zr]Zr-DFO-AR20.5 enables the visualization of tumor tissue-including metastatic lesions-with promising tumor-to-background contrast.
肿瘤相关抗原 MUC1 的高表达水平与肿瘤侵袭性、对治疗的反应差和几种肿瘤类型（包括乳腺癌、胰腺癌和上皮性卵巢癌）的生存预后差相关。在此，我们报告了一种新型基于 AR20.5 抗体的用于 MUC1 表达免疫正电子发射断层扫描（immunoPET）成像的放射性免疫偶联物的合成、表征和体内评估。为此，我们用螯合剂去铁胺（DFO）修饰 AR20.5，并标记以正电子发射放射性核素锆-89（t~3.3 d），以产生[Zr]Zr-DFO-AR20.5。在随后的在皮下表达 MUC1 的卵巢癌异种移植的裸鼠体内实验中，[Zr]Zr-DFO-AR20.5 清晰地描绘了肿瘤组织，在注射后 120 小时产生了 19.1±6.4%注入剂量/克（%ID/g）的肿瘤活性浓度，在同一时间点的肿瘤与肌肉活性浓度比为 42.4±10.6。在患有原位表达 MUC1 的卵巢癌异种移植的小鼠中进行的额外的 PET 成像实验同样表明，[Zr]Zr-DFO-AR20.5 能够可视化肿瘤组织，包括转移性病变，具有有前景的肿瘤与背景对比度。
