pet determination of specific uptake of 11 c-erlotinib by different tumor types expressing egfr, in...
TRANSCRIPT
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
HCC827, PC9Kinase Domain
Active
U87∆Extracellular Domain
Active
U87WT EGFR
Inactive
Cell Line:Mutation:
Status:
SW620No EGFR
n/a
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
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