Abstract
Immuno-PET imaging of the tumor antigen HER2/neu allows for the non-invasive detection and monitoring of oncogene expression, which is of prognostic value in patients with breast cancer. Compared with the full size antibody Trastuzumab, smaller protein tracers with more rapid blood clearance permit higher imaging contrast at earlier time points. Antigen-binding fragments (Fabs) of antibodies with moderately prolonged circulation via PASylation, a convenient biological alternative to PEGylation, offer a promising tracer format with improved pharmacokinetics for in vivo imaging. The transition radiometal 89Zr has attracted increasing interest for immuno-PET studies, thus complementing the conventional halogen radionuclide 124I. Methods: To directly compare these two radioactive labels using the same protein tracer, the recombinant αHER2 Fab fused with 200 PAS residues was either conjugated with 124I, via the Iodogen method, or coupled with deferoxamine thiocyanate, followed by complexation of 89Zr. After confirming stability of both radioconjugates and quality control in vitro, immuno-PET and biodistribution studies were performed in CD1-Foxn1nu mice bearing HER2-positive human tumor xenografts. Results: 89Zr•Df-Fab-PAS200 and 124I-Fab-PAS200 showed specific tumor uptake of 11 % ID/g and 2.3 % ID/g 24 h p.i., respectively, both with high tumor-to-blood (3.6 and 4.4) and tumor-to-muscle (20 and 43) ratios. With regard to off-target accumulation, overt 124I activity was seen in the thyroid, as expected, whereas high kidney uptake was evident for 89Zr, probably due to glomerular filtration and reabsorption of the protein tracer in proximal tubular cells. Conclusion: Both the 89Zr- and 124I-labeled version of αHER2 Fab-PAS200 allow PET tumor imaging with high contrast, while the tracer 89Zr•Df-Fab-PAS200 with its residualizing radiometal shows better in vivo stability and higher tumor uptake.
- Molecular Biology
- Monoclonal Antibodies
- PET
- Fab
- HER2
- PASylation
- plasma half-life
- positron emission tomography
- Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.