Targeted therapies have transformed the outcomes of patients with non-small-cell lung cancer (NSCLC), although only a minor subset of tumours harbours targetable alterations. Now, researchers have developed a PET tracer with a high level of specificity for activating EGFR mutations.
Researchers synthesized a PEGylated anilinoquinazoline derivative (MPG), which was then radiolabelled to enable detection using PET imaging (18F-MPG). Preliminary experiments involving NSCLC-derived cell lines confirmed the in vitro selectivity of this imaging probe for cells harbouring activating EGFR mutations, including a 90% decrease in signal in an EGFR-mutation-positive cell line pretreated with the EGFR inhibitor gefitinib. In vivo studies in mouse models confirmed the safety and metabolic stability of 18F-MPG.
In patients with NSCLC, 18F-MPG was found to selectively accumulate in tumours harbouring EGFR-activating mutations, relative to EGFR-wild-type tumours (F2, 67 = 16.30; P < 0.0001). Applying a standard uptake value (SUVmax) cut-off of 2.23 enabled the discrimination of EGFR-mutant-positive tumours from their EGFR-negative counterparts with a sensitivity of 86.5% and a specificity of 81.8%. A concordance of 84.3% was observed between 18F-MPG using this threshold and amplification refractory mutation system (ARMS)–PCR of tumour biopsy samples for determination of EGFR mutation status.
Among 38 patients who received EGFR-tyrosine-kinase inhibitors on the basis of a tumour SUVmax > 2.23 on 18F-MPG imaging, the objective response rate was 81.6%, versus 46.5% in unselected patients. In one patient, who had stable disease on gefitinib for 20 months, SUVmax was 2.31 after 6 months of treatment. Following disease regression, owing to biopsy-confirmed conversion to an EGFR-wild-type phenotype, SUVmax decreased to 2.01, suggesting sensitivity for acquired resistance. These promising findings warrant prospective validation in patients with NSCLC.
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Original Article
Sun, X. et al. A PET imaging approach for determining EGFR mutation status for improved lung cancer patient management. Sci. Transl Med. 10, eaan8840 (2018)
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Sidaway, P. PET imaging reveals EGFR mutation status. Nat Rev Clin Oncol 15, 346 (2018). https://doi.org/10.1038/s41571-018-0009-z
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DOI: https://doi.org/10.1038/s41571-018-0009-z