Studies Of Specific Molecular Imaging Probes Targeting Epidermal Growth Factor Receptor(EGFR) In Non-small Cell Lung Cancer

Lung cancer is one kind of cancers with the highest morbidity and mortality.Among all kinds of lung cancer,the number of the patients with non-small cell lung cancer?NSCLC,including squamous cell carcinoma,adenocarcinoma,large cell carcinoma et al?accounts for more than 85%of the total number of lung cancer patients.Epidermal growth factor receptor?EGFR?is a type of glycoprotein located on the cell surface,which was overexpressed in most cases of non-small cell lung cancer and closely related to the proliferation,neovascularization,invasion,metastasis and prognosis of tumors.Targeted therapy against EGFR is one of the most common treatments of non-small cell lung cancer in clinic.However,only patients with high expression and/or mutation expression of EGFR show sensitivity and high response rate to EGFR-targeted therapy.Indiscriminate use of EGFR-targeted drugs will lower overall efficacy of the treatment and delay in patient's condition.PET and SPECT imaging targeting EGFR can non-invasively provide the expression status of tumor EGFR and achieve early detection of lung cancer,screening of sensitive patients and real-time monitoring of treatment results,which is of great significance to the comprehensive evaluation of patients'overall status and the development of individualized treatment plans.Therefore,in this paper,EGFR tyrosine kinase inhibitor?EGFR-TKI?and EGFR monoclonal antibody?EGFR-Mab?showing great targeting ability to EGFR overexpressed on the non-small cell lung cancer cells were taken advantage of to design and synthesize two kinds of nuclear medicine molecular imaging probes,namely ¹⁸F-icotinib and ¹²⁵I-Necitumumab,which displayed excellent specificity to EGFR.¹⁸F-icotinib was a small molecular EGFR-TKI PET probe with quinoline structure,which was prepared by CuAAC reaction in 44.8%decay-correction radiochemical yield and>99%radiochemical purity.The Log P of ¹⁸F-icotinib was 1.28±0.04?n=6?,which meant that the probe was hydrophobic.¹⁸F-icotinib showed excellent in vitro and in vivo stability and satisfying in vitro cell binding ability.The biodistribution and PET-CT studies of A549 xenograft mice demonstrated that ¹⁸F-icotinib had specific uptake in tumors,while little accumulation was observed in the most of non-target organs.The maximum standard uptake value?SUVmax?and average standard uptake value?SUVave?in tumors were 0.65 and 0.35.¹⁸F-icotinib with great specificity and accuracy for PET imaging of EGFR-positive non-small cell lung cancer had potential for early diagnosis and prognosis evaluation of NSCLC patients.¹²⁵I-Necitumumab was an EGFR monoclonal antibody SPECT probe,which was synthesized by solid phase oxidation with>99%radiochemical purity.The Log P of ¹²⁵I-Necitumumab was-0.32±0.03?n=6?,which reflected that the probe was hydrophilic.¹²⁵I-Necitumumab existed satisfying in vitro stability and in vitro binding ability to non-small cell lung cancer cells.The biodistribution and SPECT-CT imaging of A549 and HCC827 xenograft mice showed that¹²⁵I-Necitumumab displayed specificity to tumors with high expression of EGFR,while low probe accumulation was observed in background and non-target organs.Thus,¹²⁵I-Necitumumab exhibited a significant tumor-to-background uptake ratio,making the tumors clearly visible in the SPECT-CT images.¹²⁵I-Necitumumab had great potential to be transformed into an EGFR-targeted NSCLC SPECT probe for early diagnosis and prognosis.