Fatemeh Mohammadpour-Ghazi - Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran
Hassan Yousefnia - Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran
GhasemAli Divband - Khatam PET/CT Center, Khatam-Al-Anbia Hospital, Tehran, Iran
Samaneh Zolghadri - Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran
Behrouz Alirezapour - Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran
Fatemeh Shakeri - Department of Clinical Biochemistry, Faculty of Medical Sciences, Zanjan University Medical Sciences, Zanjan, Iran

Objective(s): Due to the suitable physical characteristics of ۸۹Zr as a PET radionuclide and affinity of Trastuzumab monoclonal antibody against HER۲, [۸۹Zr]Zr-Trastuzumab was prepared and went through preclinical evaluations for ultimate human applications.Methods: ۸۹Zr was produced by using ۸۹Y(p,n)۸۹Zr reaction at a ۳۰ MeV cyclotron (radionuclide purity>۹۹.۹%, specific activity of ۱۷ GBq/µg). p-SCN-Bn-Deferoxamine (DFO); was conjugated to trastuzumab, followed by labeling with ۸۹Zr in oxalate form at optimized condition. Cell binding, internalization and, radioimmuno-activity assays were studied using HER۲+ BT۴۷۴ and HER۲- CHO cell lines. Finally, the biodistribution of the radioimmunoconjugate was assessed in normal and HER۲+ BT۴۷۴ tumor-bearing mice using tissue counting and imaging at different intervals after injection. Also, a woman with HER۲-positive metastatic breast cancer under treatment with Herceptin underwent both [۸۹Zr]Zr-Trastuzumab and, [۱۸F]FDG PET/CTs.Results: ۸۹Zr was produced with high radionuclidic and radiochemical purities (>۹۹%) and [۸۹Zr]Zr-DFO-Trastuzumab was prepared with radiochemical purity of >۹۸% and specific activity of ۹.۸۵ GBq/µmol. The radioimmunoconjugate was stable both in PBS buffer and in human serum for at least ۴۸ h. The radioimmunoactivity assay demonstrated about ۷۰% of [۸۹Zr]Zr-DFO-Trastuzumab is bound to the BT۴۷۴ cells at the number of ۲۵۰×۱۰۶ cells. Cell binding studies showed that about ۲۸% of radioimmunoconjugate is attached to BT۴۷۴ cells after ۹۰ min. Internalization studies showed that ۵۰% of [۸۹Zr]Zr-Trastuzumab is internalized to BT۴۷۴ cells only in ۶ h. The biodistribution study of the labeled compound in normal mice demonstrated the same pattern of the monoclonal antibodies which is entirely different from the biodistribution of free ۸۹Zr. Biodistribution and imaging studies in tumor-bearing mice showed the significant uptake values of [۸۹Zr]Zr-Trastuzumab in tumor sites. [۸۹Zr]Zr-Trastuzumab PET/CT revealed metastatic lesions documented previously with [۱۸F]FDG PET/CT scan in a woman with breast cancer who was under treatment with Herceptin. Although the [۱۸F]FDG PET/CT scan had better quality images, the valuable and unique advantage of [۸۹Zr]Zr-Trastuzumab PET/CT is delineating HER۲+ metastasis, which is essential in diagnosis and HER۲-based treatments.Conclusion: The prepared [۸۹Zr]Zr-Trastuzumab has a high potential radio-pharmaceutical for immune-PET imaging of the patients with HER۲+ tumors.

۸۹Zr, Trastuzumab, HER۲ positive tumors, Breast Cancer