Tran T Hoang1,2, Komal Mandleywala1, Tara Viray1, Kel Vin Tan1,3, Jason S Lewis4,5,6,7,8, Patricia M R Pereira9,10. 1. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. 2. Department of Pharmacology, Weill Cornell Medical College, New York, NY, 10065, USA. 3. Department of Diagnostic Radiology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China. 4. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. lewisj2@mskcc.org. 5. Department of Pharmacology, Weill Cornell Medical College, New York, NY, 10065, USA. lewisj2@mskcc.org. 6. Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. lewisj2@mskcc.org. 7. Department of Radiology, Weill Cornell Medical College, New York, NY, 10065, USA. lewisj2@mskcc.org. 8. Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. lewisj2@mskcc.org. 9. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. ribeiropereirap@wustl.edu. 10. Department of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, 63110, USA. ribeiropereirap@wustl.edu.
Abstract
PURPOSE: Immuno-positron emission tomography (immunoPET) combines the specificity of an antibody with the sensitivity of PET to image dysregulated pathways in cancer. This study examines the performance of immunoPET using the radioimmunoconjugate [89Zr]Zr-DFO-Panitumumab to detect epidermal growth factor receptor (EGFR) expression in an orthotopic model of bladder cancer (BCa). PROCEDURES: Expression and quantification of EGFR receptors were confirmed in four different BCa cell lines. Binding assays validated [89Zr]Zr-DFO-Panitumumab specificity for EGFR-expressing UMUC3 BCa cells. Subcutaneous and orthotopic UMUC3 xenografts were then used for PET imaging and ex vivo biodistribution of the radioimmunoconjugate. Control cohorts included non-tumor mice, 89Zr-labeled non-specific IgG, and blocking experiments. RESULTS: [89Zr]Zr-DFO-Panitumumab binds specifically to EGFR-expressing UMUC3 cells with a Bmax value of 5.9 × 104 EGFRs/cell in vitro. ImmunoPET/CT images show localization of the antibody in subcutaneous UMUC3 xenografts and murine bladder tumors. In the orthotopic model, the immunoPET signal correlates with the respective tumor volume. Ex vivo biodistribution analysis further confirmed imaging results. CONCLUSION: The preclinical data presents a proof of concept for utilizing EGFR-targeted immunoPET to image BCa with altered EGFR protein levels.
PURPOSE: Immuno-positron emission tomography (immunoPET) combines the specificity of an antibody with the sensitivity of PET to image dysregulated pathways in cancer. This study examines the performance of immunoPET using the radioimmunoconjugate [89Zr]Zr-DFO-Panitumumab to detect epidermal growth factor receptor (EGFR) expression in an orthotopic model of bladder cancer (BCa). PROCEDURES: Expression and quantification of EGFR receptors were confirmed in four different BCa cell lines. Binding assays validated [89Zr]Zr-DFO-Panitumumab specificity for EGFR-expressing UMUC3 BCa cells. Subcutaneous and orthotopic UMUC3 xenografts were then used for PET imaging and ex vivo biodistribution of the radioimmunoconjugate. Control cohorts included non-tumor mice, 89Zr-labeled non-specific IgG, and blocking experiments. RESULTS: [89Zr]Zr-DFO-Panitumumab binds specifically to EGFR-expressing UMUC3 cells with a Bmax value of 5.9 × 104 EGFRs/cell in vitro. ImmunoPET/CT images show localization of the antibody in subcutaneous UMUC3 xenografts and murine bladder tumors. In the orthotopic model, the immunoPET signal correlates with the respective tumor volume. Ex vivo biodistribution analysis further confirmed imaging results. CONCLUSION: The preclinical data presents a proof of concept for utilizing EGFR-targeted immunoPET to image BCa with altered EGFR protein levels.
Authors: Freddy E Escorcia; Jeffrey M Steckler; Dalya Abdel-Atti; Eric W Price; Sean D Carlin; Wolfgang W Scholz; Jason S Lewis; Jacob L Houghton Journal: Mol Imaging Biol Date: 2018-10 Impact factor: 3.488