Biophotonics discoveryPub Date : 2024-04-01Epub Date: 2024-05-28DOI: 10.1117/1.bios.1.1.015003
Jesse D Ivers, Nagavenkatasai Puvvada, Charles M Quick, Narasimhan Rajaram
{"title":"Investigating the relationship between hypoxia, hypoxia-inducible factor 1, and the optical redox ratio in response to radiation therapy.","authors":"Jesse D Ivers, Nagavenkatasai Puvvada, Charles M Quick, Narasimhan Rajaram","doi":"10.1117/1.bios.1.1.015003","DOIUrl":"10.1117/1.bios.1.1.015003","url":null,"abstract":"<p><strong>Significance: </strong>Radiation resistance is a major contributor to cancer treatment failure and is likely driven by multiple pathways. Multivariate visualization that preserves the spatial co-localization of factors could aid in understanding mechanisms of resistance and identifying biomarkers of response.</p><p><strong>Aim: </strong>We aim to investigate the spatial and temporal relationship between hypoxia, hypoxia-inducible factor 1 (HIF-1<i>α</i>), and metabolism in response to radiation therapy in two cell lines of known radiation resistance and sensitivity.</p><p><strong>Approach: </strong>Two-photon excited fluorescence and fluorescence lifetime imaging microscopy were used to quantify the optical redox ratio (ORR) and NAD(P)H fluorescent lifetime and bound fraction in frozen tumor sections and co-registered with immunohistochemical stain-based imaging of hypoxic fraction and HIF-1<i>α</i>.</p><p><strong>Results: </strong>Histogram analysis of hypoxia, HIF-1<i>α</i>, and ORR revealed an increase in the ORR in regions of low hypoxia and high HIF-1<i>α</i>, indicating that the stabilization of HIF-1<i>α</i> is likely due to an increase in reactive oxygen species following radiation therapy. In addition, the bound NAD(P)H fraction was higher in regions with a low ORR in resistant tumors following radiation, suggesting an increase in fatty acid synthesis.</p><p><strong>Conclusions: </strong>A multivariate histogram approach can reveal hidden trends not observed in bulk analysis of tumor images and may be useful in understanding biomarkers and mechanisms of radiation resistance.</p>","PeriodicalId":519981,"journal":{"name":"Biophotonics discovery","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}