Human Absorbed Dose Estimation of 89Zr-Anti-HER2 Complex Based on Animal Data
نویسندگان
1 Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, 14155-1339, Iran.
2 Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, 14155-1339, Iran.
3 Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, 14155-1339, Iran.
doi
10.22038/ijmp.2025.78414.2386چکیده
Introduction: This study aimed to estimate the radiation absorbed dose of human organs after injection of a high-potential PET radioimmunoconjugate of HER2+ breast cancers using the medical internal radiation dose (MIRD) method and the radiation dose assessment resource (RADAR) formalism. Material and Methods: 89Zr was produced by the nuclear reaction of 89Y with protons (p,n), and purified by a column filled with ZR resin. The radionuclide, chemical, and radiochemical purities of the 89Zr solution were measured using gamma spectrometry, inductively coupled plasma (ICP), and radio-thin-layer chromatography (RTLC) methods, respectively. The conjugated anti-HER2 with deferoxamine (DFO) was labeled with an in-house produced 89Zr at the optimized condition to prepare 89Zr-Anti-HER2, and its radiochemical purity was assessed by the RTLC method. The stability of the radioimmunoconjugate was assessed in Phosphate-buffered saline (PBS) buffer and human serum at various intervals. Biodistribution of the final complex was studied in tumor-bearing mice at specified intervals. Finally, the absorbed dose of human organs was estimated using the MIRD method and RADAR formalism based on animal data. Results: 89Zr radionuclide was produced by the radiochemical and radionuclide purities of >99%, and >99.99%, respectively, while the chemical impurities were < 0.1 ppm. The radiolabeled antibody was prepared with radiochemical purity >98% at optimized conditions. The results showed the liver received the maximum amount of the absorbed dose of 1.49 mGy/MBq, and other organs received < 0.87 mGy/MBq. Conclusion: 89Zr-Anti-HER2 complex is a promising agent for PET imaging of patients with HER2+ tumors with high safety in the country.