TY - JOUR T1 - In vivo micro-imaging of apoptosis in a murine xenograft model of human lung adenocarcinoma JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - 3290 AU - Florian Guisier AU - Mathieu Salaun AU - Pierre Bohn AU - Pierre Vera AU - Luc Thiberville Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/3290.abstract N2 - Background: Resistance to apoptosis is a hallmark of cancer that can be reversed by chemotherapy drugs and targeted therapies, including cisplatin and erlotinib. In vivo in situ imaging of apoptosis may be useful for the early assessment of drug activity. The aim of this study is to investigate whether in vivo micro-imaging of apoptosis is correlated with treatment response in a murine xenograft model of human lung cancer. Methods: A549 (EGFR wild type), H1650 (carrying EGFR exon 19 deletion, sensitive to Erlotinib) and H1975 (carrying EGFR mutations L858R and T790M, resistant to Erlotinib) cell lines were used to induce subcutaneous tumors in Nude mice. In vivo micro-imaging of apoptosis in experimental tumors was performed using fibered confocal fluorescence microscopy (FCFM) after intra-venous injection of a fluorogenic caspase 3 substrate. Tumors were treated by cisplatin (10mg/kg) (5 mice, A549 xenografts), erlotinib (25mg/kg) (6 mice, 2 A549, 2 H1650, 2 H1975), or vehicle (6 mice, 2 A549, 2 H1650, 2 H1975). Results: In A549 xenografts treated by cisplatin, apoptosis was detected in vivo at 24h post-treatment. Fluorescence intensity ratio (FIR) was significantly higher compared to untreated tumors (16.9+/-3.1 vs 4.8+/-2.1 respectively, p<0.001). 24h after treatment by erlotinib, FIR in H1650 erlotinib sensitive tumors was significantly higher than in A549 tumors, and than in H1975 erlotinib resistant tumors (12.2+/-2.4 vs 6.1+/-1.2 vs 1.9+/-0.7 respectively, p<0.01). Conclusion : In vivo micro-imaging of apoptosis is possible and appears able to predict tumor response in a xenograft model of EGFR mutated human lung adenocarcinoma. ER -