pet determination of specific uptake of 11 c-erlotinib by different tumor types expressing egfr, in...
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![Page 1: 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,](https://reader036.vdocuments.us/reader036/viewer/2022082422/56649ef45503460f94c07775/html5/thumbnails/1.jpg)
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
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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
HCC827, PC9Kinase Domain
Active
U87∆Extracellular Domain
Active
U87WT EGFR
Inactive
Cell Line:Mutation:
Status:
SW620No EGFR
n/a
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KINASE DOMAIN MUTANT TUMORS
0 20 40 60 80 100 1200
0.5
1
1.5
2
Time (min)
SU
V
0 20 40 60 80 100 1200
0.5
1
1.5
2
Time (min)
SU
V
Tracer Experiment Excess Cold Drug
SW620 (▲)
Muscle (○)
HCC827 (■)
PC9 (♦)
HCC827, PC9KD MutantActivated EGFR
no EGFR
KD Mutant
KD Mutant
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HCC827 PC9 SW620 U87 U87∆-1
0
1
2
3
4
5
6
7
8
9
tracer experiment
excess cold drug
Me
an
BP
SPECIFIC BINDING
** p<0.05 * p=0.06
**
*
NS NSNS
n= 3 3 3 3 1 1 3 2 3 2
KDActive
ECDActive
WT EGFRInactive
Mutation:
Status:No EGFR
n/aKD
Active