Abstract 5616: Optical metabolic imaging of treatment-naive human NSCLC to determine long-term outcome
Authors: Diaz Paola Monterroso 
Published: April 2023

Abstract
Lung cancer remains the leading cause of cancer deaths in the US and worldwide.​ The five-year survival rate of patients with non-small cell lung carcinoma (NSCLC) remains significantly low given that over half present with locally advanced or metastatic disease at time of diagnosis, and experience tumor recurrence following therapeutic intervention.​Current evaluation techniques to assess treatment response are lacking, given they are implemented several weeks after treatment completion and are solely based on anatomical changes in tumor size, forgoing other criteria such as functional or metabolic changes.​ There is a critical need to identify markers early on following diagnosis that are indicative of patient long-term outcome. Two photon microscopy (TPM) techniques are well-suited to provide non-invasive high-resolution information on cell metabolism within three-dimensional tissue. Specifically, two-photon excited fluorescence imaging of autofluorescent cofactors, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), can be used to metabolically characterize cancerous tissue. The goal of this study is to utilize the optical redox ratio (ORR) of FAD/[NADH+FAD] autofluorescence and NADH fluorescence lifetime decay to identify measurable differences in optical metabolic endpoints of human NSCLC that are indicative of their long-term outcome. Twenty-nine NSCLC specimens were obtained from the Lung Cancer Biospecimen Resource Network. They were resected from the lung prior to the patient receiving therapy. Clinical detail reports were used to evaluate the follow-up data of each patient and classify them into groups that reflected their eventual outcomes: responder (N=21), non-responder (N=18), non-metastatic (N=25), and metastatic (N=14). TPM was used to determine the ORR for each sample. NADH lifetime images were collected and fit to a biexponential model to separate the short (A1) and long (A2) components of free and bound NADH. We observed a significantly higher optical redox ratio for tumors within the metastatic group compared to non-metastatic. ​This is consistent with previous findings from our lab that revealed increases in the ORR with increasing metastatic potential in cells, as well as other studies reporting a decrease in NADH concentration in metastatic cancers.​ Additionally, a significantly shorter mean NADH lifetime in the metastatic tumor group was revealed when compared to non-metastatic. This stands in agreement with other studies highlighting decreases in the average lifetime of NADH in metastatic cells compared to non-metastatic. These results demonstrate the feasibility of using optical imaging of autofluorescence and lifetimes of metabolic cofactors to characterize treatment-naïve primary NSCLC tumors and determine differences in their optical metabolic endpoints that are indicative of their long-term outcome.
Citation Format: Paola Monterroso Diaz. Optical metabolic imaging of treatment-naive human NSCLC to determine long-term outcome. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5616.