Abstract:
:Mutations in the kinase domain of epidermal growth factor receptor (EGFR) have high levels of basal receptor phosphorylation and are associated with clinical responsiveness to Iressa in patients with nonsmall cell lung cancer (NSCLC). This study aimed to assess the feasibility of morpholino-[(124)I]IPQA derivative as an in vivo PET imaging tool for the expression of different EGFR mutants in NSCLC. In vitro radiotracer accumulation and washout studies demonstrated a rapid accumulation and progressive retention after washout of morpholino-[(131)I]IPQA derivative in high EGFR-expressing H1299 NSCLC derivative cell lines (L858R and E746-A750 del cell lines), but not in EGFR-transfected H1299 cell line and vector-transfected H1299 cell line. Using the morpholino-[(124)I]IPQA derivative, we obtained noninvasive microPET images of EGFR activity in L858R and E746-A750 del subcutaneous tumor xenografts, but not in subcutaneous tumor xenografts grown form control cell line. Different EGFR mutant (activity) tumors have a different morpholino-[ (∗) I]IPQA derivative uptake. However, it still needs to modify the structure of IPQA to increase its water solubility and reduce hepatobiliary clearance. Morpholino-[(124)I]IPQA derivative may be a potential probe for selection of the candidate patients suffering from NSCLC for the small molecule tyrosine kinase inhibitor therapy (e.g., Iressa) in the future.
journal_name
Biomed Res Intjournal_title
BioMed research internationalauthors
Yeh SH,Lin CF,Kong FL,Wang HE,Hsieh YJ,Gelovani JG,Liu RSdoi
10.1155/2013/549359subject
Has Abstractpub_date
2013-01-01 00:00:00pages
549359eissn
2314-6133issn
2314-6141journal_volume
2013pub_type
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journal_title:BioMed research international
pub_type: 杂志文章,评审
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doi:10.1155/2016/1310342
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doi:10.1155/2018/5089270
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journal_title:BioMed research international
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doi:10.1155/2016/7618342
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