Development and Evaluation of 18F-IRS for Molecular Imaging Mutant EGF Receptors in NSCLC

Abstract

To prepare and evaluate a new radiotracer 18F-IRS for molecular imaging mutant EGF Receptors in vitro and vivo. Uptake and efflux of 18F-IRS were performed with four NSCLC cell lines including HCC827, H1975, H358 and H520. In vivo tumor targeting and pharmacokinetics of the radiotracers were also evaluated in HCC827, H1975, H358 and H520 tumor-bearing nude mice by PET/CT imaging. Ex vivo biodistribution assays were performed to quantify the accumulation of 18F-IRS in vivo. We also performed 18F-IRS PET/CT imaging of three patients with NSCLC. We labeled this small molecule with QD620 for flow cytometry and confocal imaging analyses. The uptakes of 18F-IRS by HCC827 and HCC827 tumors were significantly higher than those of H358, H1975 and H520, and they were reduced by the addition of 100 μM of gefitinib. Biodistribution experiments showed an accumulation of 18F-IRS in tumors of HCC827 xenografts. Flow cytometry and confocal imaging with QD620-IRS further demonstrated that binding specifically to HCC827 cells. 18F-IRS accumulation was preferential in the tumor, which was NSCLC with responsive EGFR exon 19 deleted. 18F-IRS showed high binding stability and specificity to 19 exon deleted EGFR mutation in vitro and vivo.

Folate receptor‐targeted 19F MR molecular imaging and proliferation evaluation of lung cancer

“…After 1 hour, the animals were subjected to general anesthesia via aspiration of isoflurane, then fixed in a PET/CT imaging system (GE Discovery 750 Elite, GE Healthcare), and 18 F‐FLT PET/CT imaging was performed. Images reconstruction and radioactivity concentrations measurement were performed on an AW4.6 workstation (GE Healthcare) with a 2D ordered‐subset expectation maximization (OSEM) algorithm . The values were expressed in terms of percentage injected dose per gram (% ID/g) based on the known administered activities, and the tumor to muscle ratios were calculated and compared between the two groups.…”

“…Images reconstruction and radioactivity concentrations measurement were performed on an AW4.6 workstation (GE Healthcare) with a 2D ordered-subset expectation maximization (OSEM) algorithm. 23 The values were expressed in terms of percentage injected dose per gram (% ID/g) based on the known administered activities, and the tumor to muscle ratios were calculated and compared between the two groups.…”

Molecular Imaging in Cancer Drug Development

“…Molecular imaging can potentially provide information on the mutational status of EGFR lesions and thereby facilitate drug development by improving patient selection. 18 F-N-(3-chloro-4-fluorophenyl)-7-(2(2-(2-(2-(4-fluorine)ethoxy)ethoxy)-ethoxy)-6-(3-morpholinopropoxy)quinazolin-4-amine ( 18 F-IRS) is a novel radiotracer developed to image the EGFR exon 19 deletion, an EGFR aberration leading to constitutive EGFR activation (12). Preclinically, 18 F-IRS showed preferential uptake in tumors with EGFR exon 19 deletion (12).…”

“…observed in tumor lesions with an exon 19 deletion from 3 NSCLC patients (12). Imaging of the mutational status of NSCLC was also pursued using 18 F-ODS2004436, a compound chosen on the basis of EGFR selectivity.…”

Development of a SPECT Tracer to Image c-Met Expression in a Xenograft Model of Non–Small Cell Lung Cancer

“…Two NSCLC cell lines were selected-H1993 (high c-Met expression) and H1299 (no c-Met expression)-and cultured as previously reported (22).…”