Non-invasive Visualization Of The Epidermal Growth Factor Receptor In Non-small Cell Lung Cancer Patients By Positron Emission Tomography And ¹¹C-PD153035

Aims1,To investigate the feasibility of EGFR molecular imaging with selective radiotracer¹¹C-PD153035 and PET/CT in non-small cell lung cancer patients.2,To identify the correlation between tumor ¹¹C-PD153035 uptake and EGFR genecopies,protein expression and gene mutation.3,To evaluate the radiation biodistribution and dosimetry of ¹¹C-PD153035 inhumans.Contents1,¹¹C-PD153035 molecular imaging in NSCLC patients.2,Correlation between EGFR molecular images and EGFR pattern in vivo.3,Radiation dosimetry of ¹¹C-PD 153035in humans.Methods1,Synthesis of 11C-PD153035The general procedure of synthesis and carbon-11 radiolabelled of PD153035(ABX advanced biochemical compounds,Germany)was performed in Tracer labFXc system (GE Healthcare,USA).2,PET/CT scanningPET scan was performed by a combined PET/CT scanner (Discovery LS,GEHealthcare,USA)with a multislice helical CT.The standardized uptake value (SUV)was calculated.Radiation dosimetry computation was calculated by the MIRDOSE3.0 software with organ residence time.3,Detection of EGFR gene copies by FISH.4,Detection of EGFR protein expression by Western Blot and IHC.5,Detection of EGFR gene mutation by PCR and gene sequencing.Results1,Uptake of ¹¹C-PD153035 Correlated with EGFR pattern in tumors¹¹C-PD153035 uptake was observed in 9 out of 14 NSCLC patients (mean SUV3.94±1.06,range 0.8-5.9)and the biodistribution study further demonstratedaccumulation of radioactivity in the tumor mass.The SUVmax of ¹¹C-PD153035 molecular images did not correlate with tumor size and injection dose of the tracer.Aclosely correlation between SUVmax and EGFR protein expression as determined byIHC (r=0.84,P=0.005)was observed but not with the result of Western blot analysis(r=0.442,P=0.114),as well as EGFR exon 19 (r=-0.078,P=0.790)or exon 21(r=0.118,P=0.689)gene mutation and EGFR gene copies (r=0.358,P=0.209).2,Biodistribution of ¹¹C-PD153035 in HumansThe highest SUVs in solid organs 60 min after injection were found in thebladder (SUV,5.29±1.09),followed by the gallbladder (SUV,2.67±1.06),thekidneys (SUV,2.15±0.69),the bile secreted into the small intestine (SUV,1.88±0.78)and the liver (SUV,1.09±0.81).Low activities in the lung and muscles60 min after injection were found with SUVs of 0.22±0.07 and 0.14±0.05,respectively.In general,the areas of highest activity were the urogenital tract (kidneys,ureters,and bladder),followed by liver,gallbladder and the small intestine.Bloodpool activity was only moderate and declined over time.Background activities in themuscles and lungs were low.3,Radiation dosimetry of ¹¹C-PD153035The highest absorbed dose was present in the urinary bladder wall(6.08E-02±1.85E-02mGy/MBq),followed by the gallbladder (2.40E-02±8.01E-03mGy/MBq),kidney (1.42E-02±6.36E-03mGy/MBq)and the liver(9.10E-03±1.65E-03)The effective dose equivalent was 7.43E-03±1.10E-03mSv/MBq and the dose-limiting organ (organ with the largest absorbed dose)wasthe urinary bladder.Conclusions1,¹¹C-PD153035 is rapidly cleared from the body,largely by the kidneys and liver.An effective radiation dose is substantially less than the estimated maximum radiationburden caused by carbon-11 tracers which means serial examinations in the samesubject seem feasible from the viewpoint of radiation safety.2,¹¹C-PD153035 is a promising ligand for the investigation of EGFR in humans,especially in chest tumor such as NSCLC.