Nucl Med Mol Imaging.  2020 Apr;54(2):114-119. 10.1007/s13139-020-00638-7.

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

• Richter A
• Knorr K
• Schlapschy M
• Robu S
• Morath V
• Mendler C
• Yen HY
• Steiger K
• Kiechle M
• Weber W
• Skerra A
• Schwaiger M

• KMID: 2500065
• DOI: http://doi.org/10.1007/s13139-020-00638-7

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.

Keyword

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