pet determination of specific uptake of 11 c-erlotinib by different tumor types expressing egfr, in...

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