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PET determination of specific uptake of 11C-erlotinib by different tumor types expressing EGFR, in vivo, through kinetic modeling J. Ryan Petrulli1,4, Jenna M. Sullivan1,4, Ming-Qiang Zheng2,4, Yiyun Huang2,4, Joseph N. Contessa3, Evan D. Morris1,2,4 1. Biomedical Engineering 2. Diagnostic Radiology 3. Therapeutic Radiology 4. Yale PET Center Yale University, New Haven, CT, USA METHODS • Subjects: nude mice implanted with 2-3 tumor xenografts • Human cancer cell lines: SW620, U87, HCC827, PC9, and U87∆ • Scans: Siemens Focus 220; 11C-erlotinib injections with or without excess erlotinib • Analysis: – Regions of interest (ROI) drawn on summed images; regional timeactivity curves – Kinetic modeling with SRTM to produce BP – Statistical comparison between BP in each xenograft and drug condition Cell Line: SW620 Mutation: No EGFR n/a Status: U87 WT EGFR Inactive HCC827, PC9 Kinase Domain Active U87∆ Extracellular Domain Active KINASE DOMAIN MUTANT TUMORS Tracer Experiment Excess Cold Drug 2 2 KD Mutant 1 KD Mutant 1.5 SUV SUV 1.5 1 0.5 0.5 no EGFR 0 0 0 50 Time (min) 100 0 50 100 Time (min) SW620 (▲) Muscle (○) PC9 (♦) HCC827 (■) HCC827, PC9 KD Mutant Activated EGFR SPECIFIC BINDING 9 ** 8 tracer experiment 7 excess cold drug Mean BP 6 5 * 4 NS 3 NS 2 NS 1 0 n= 3 3 3 3 1 1 3 2 3 2 -1 HCC827 Mutation: KD Status: Active ** p<0.05 * p=0.06 PC9 SW620 U87 U87∆ KD Active No EGFR n/a WT EGFR Inactive ECD Active