First In-Human Medical Imaging with a PASylated ⁸⁹Zr-Labeled Anti-HER2 Fab-Fragment in a Patient with Metastatic Breast Cancer

Purpose: PASylation® offers the ability to systematically tune and optimize the pharmacokinetics of protein tracers for molecular imaging. Here we report the first clinical translation of a PASylated Fab fragment (⁸⁹Zr∙Df-HER2-Fab-PAS₂₀₀) for the molecular imaging of tumor-related HER2 expression. Methods: A patient with HER2-positive metastatic breast cancer received 37 MBq of ⁸⁹Zr∙Df-HER2-Fab-PAS₂₀₀ at a total mass dose of 70 μg. PET/CT was carried out 6, 24, and 45 h after injection, followed by image analysis of biodistribution, normal organ uptake, and lesion targeting. Results: Images show a biodistribution typical for protein tracers, characterized by a prominent blood pool 6 h p.i., which decreased over time. Lesions were detectable as early as 24 h p.i. ⁸⁹Zr∙Df-HER2-Fab-PAS₂₀₀ was tolerated well. Conclusion: This study demonstrates that a PASylated Fab tracer shows appropriate blood clearance to allow sensitive visualization of small tumor lesions in a clinical setting.