PET determination of specific uptake of 11C-erlotinib by different tumor types expressing EGFR, in vivo, through kinetic modeling J. Ryan Petrulli1,4,

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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 time-activity curves Kinetic modeling with SRTM to produce BP Statistical comparison between BP in each xenograft and drug condition U87, U87D = glioblastoma HCC827, PC9 Kinase Domain Active U87∆ Extracellular Domain U87 WT EGFR Inactive Cell Line: Mutation: Status: SW620 No EGFR n/a

KINASE DOMAIN MUTANT TUMORS Tracer Experiment Excess Cold Drug KD Mutant KD Mutant no EGFR SW620 (▲) Muscle (○) HCC827 (■) PC9 (♦) HCC827, PC9 KD Mutant Activated EGFR

SPECIFIC BINDING ** * NS NS NS ** p<0.05 * p=0.06 Mutation: KD Active KD Active ECD WT EGFR Inactive No EGFR n/a Status: ** p<0.05 * p=0.06