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METHODS

PET determination of specific uptake of 11 C-erlotinib by different tumor types expressing EGFR, in vivo, through kinetic modeling. J. Ryan Petrulli 1,4 , Jenna M. Sullivan 1,4 , Ming-Qiang Zheng 2,4 , Yiyun Huang 2,4 , Joseph N. Contessa 3 , Evan D. Morris 1,2,4 1. Biomedical Engineering

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METHODS

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  1. 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

  2. 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 Cell Line: SW620 No EGFR n/a Mutation: Status: U87 WT EGFR Inactive U87∆ Extracellular Domain Active HCC827, PC9 Kinase Domain Active

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

  4. SPECIFIC BINDING ** * NS NS NS n= 3 3 3 3 1 1 3 2 3 2 Mutation: KD Active No EGFR n/a Status: ** p<0.05 * p=0.06 WT EGFR Inactive KD Active ECD Active

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