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