Abstract
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 (t1/2 ~3.3 d) to produce [89Zr]Zr-DFO-AR20.5. In subsequent in vivo experiments in athymic nude mice bearing subcutaneous MUC1-expressing ovarian cancer xenografts, [89Zr]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 [89Zr]Zr-DFO-AR20.5 enables the visualization of tumor tissue—including metastatic lesions—with promising tumor-to-background contrast.
Highlights
Mucins are high molecular weight transmembrane glycoproteins that are expressed on the surface of normal and malignant epithelial cells and play a diverse collection of roles, ranging from the protection of the cell surface to the regulation of cellular adhesion [1,2,3]
After the final imaging time point, the orthotopic tumor-bearing mice were sacrificed, and selected tissues were harvested, washed, weighed, and assayed for 89Zr using a gamma counter to produce quantitative biodistribution data. These data are consistent with the imaging results, pointing to a tumoral activity concentration of 11.3 ± 7.1 %ID/g at 120 p.i. and significant accumulation in the liver (10.5 ± 2.4 %ID/g) and spleen (6.1 ± 0.3 %ID/g)
MUC1 and circulating radioimmunoconjugate that were deposited in these tissues
Summary
Fung 1,2,† , Delphine Vivier 1,† , Outi Keinänen 1,3 , Elaheh Khozeimeh Sarbisheh 4 , Eric W.
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