Document Type

Article

Publication Date

5-28-2024

Keywords

Multiphoton microscopy, Radiation resistance, Cancer, Histogram analysis, Multivariate, Tumor microenvironment, Tumors, Histograms, Hypoxia, Radiotherapy, Resistance, Autofluorescence, Animals, Cancer, Mode conditioning cables, Oxygen

Abstract

Significance

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.

Aim

We aim to investigate the spatial and temporal relationship between hypoxia, hypoxia-inducible factor 1 (HIF-1α), and metabolism in response to radiation therapy in two cell lines of known radiation resistance and sensitivity.

Approach

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-1α.

Results

Histogram analysis of hypoxia, HIF-1α, and ORR revealed an increase in the ORR in regions of low hypoxia and high HIF-1α, indicating that the stabilization of HIF-1α 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.

Conclusions

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.

Additional Files
BIOS_1_1_015003_ds001.pdf (670 kB)
Histograms

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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