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

Abstract

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.

Keywords: 89Zr; Breast cancer (BCa); Fab fragment; Human epidermal growth factor receptor 2 (HER2); Imaging; PASylation.

Fig. 1

Structure of a PASylated Fab fragment in comparison with a full-size antibody

Fig. 2

Biodistribution and lesion targeting of ⁸⁹Zr∙Df-HER2-Fab-PAS₂₀₀ in a mBCa patient. a Whole-body MIP images of ⁸⁹Zr∙Df-HER2-Fab-PAS₂₀₀. b Magnification of ⁸⁹Zr∙Df-HER2-Fab-PAS₂₀₀ accumulation in axillary lymph node metastases (blue arrow) and in the presumed primary tumor (green arrow) 24 h after injection. c Overlay of PET/CT images in the region of the presumed primary tumor in the left breast. d MRT scan of multiple brain metastases (yellow arrows)