J. D. Predina1, A. Newton1, J. Keating1, O. Venegas1, S. Singhal1 1University Of Pennsylvania,Philadelphia, PA, USA
Introduction: Postoperative cancer recurrences occur in 40% of patients undergoing resection for NSCLC. Such recurrence rates are partially attributable to limitations in intraoperative tools that assist the surgeon in disease identification. We hypothesized that intraoperative imaging using a fluorescent imaging agent, 5-aminolevulinic acid (5-ALA), could enhance intraoperative identification of NSCLC cancer deposits that would otherwise be missed.
Methods: The murine NSCLC line, TC1, was cultured in vitro and exposed 1 mM concentrations of 5-ALA for 0 to 24 hours. Fluorescence was assessed with flow cytometry. Next, in vivo feasibility of systemic 5-ALA was tested using a small animal model of NSCLC cancer surgery (n=25).
Results: In vitro, TC1 exhibited high levels of fluorescence after 2 hours of exposure to 5-ALA. Additional exposure did not augment signal. Involving in vivo studies, systemic administration of 5-ALA helped identify the presence of residual tumor cells after surgery in 17/25 resections. The mean residual tumor size was 1.8mm, with a mean fluorescence signal-to-background ratio (SBR) of 4.1. Of note, minimal fluorescence was noted within thoracic structures including lung parenchyma, pericardium and pleura.
Conclusion: Systemic 5-ALA reliably accumulates in murine models of NSCLC and helps identify residual disease deposits. This data supports additional pre-clinical studies which will set the basis for a Human Trial utilizing 5-ALA to enhance NSCLC resection.