Synthesize of a novel 89Zr labeled HER2 affibody and its application study in tumor PET imaging
Abstract Background: Human epidermal growth factor receptor-2 (HER2) is an important biomarker for tumor diagnosis and therapy. Affibody is an ideal vector for preparing HER2 specific probes due to the advantages such as high affinity and rapid blood clearance etc. 89Zr is a novel PET imaging isotope with long half-lives and suitable for tracking biological processes for longer periods. In this study, a novel 89Zr labeled HER2 affibody, 89Zr-DFO-MAL-Cys-MZHER2, was synthesized and its imaging properties were also evaluated. Results: The precursors, DFO-MAL-Cys-MZHER2, were obtained with the yields of nearly 50%. The yields of 89Zr -DFO-MAL-Cys-MZHER2 were 90.2±1.9% and the radiopurities were more than 95%. The total synthesis time was only 30 minutes. The probes were stable in PBS and serum. The tracer accumulated in HER2 overexpression human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe highly retained in SKOV-3 xenografts even for 48 hours. The tumors were visualized with good contrast to normal tissue. ROI analysis revealed that the average uptakes in the tumor were greater than 5 %ID/g. On the contrary, the counterparts of MCF-7 tumors kept low levels of (~1%ID/g). The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the blood and normal organs, and mainly excreted through the urinary system. Conclusion: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. 89Zr-DFO-MAL-MZHER is a potential candidate for monitoring HER2 expression and may play specific roles in clinical cancer theranostics.