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Molecular Imaging and Biology

, Volume 21, Issue 3, pp 426–435 | Cite as

Optical Redox Imaging of Lonidamine Treatment Response of Melanoma Cells and Xenografts

  • He N. XuEmail author
  • Min Feng
  • Kavindra Nath
  • David Nelson
  • Jeff Roman
  • Huaqing Zhao
  • Zhenwu Lin
  • Jerry Glickson
  • Lin Z. LiEmail author
Research Article

Abstract

Purpose

Fluorescence of co-enzyme reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp) provides a sensitive measure of the mitochondrial redox state and cellular metabolism. By imaging NADH and Fp, we investigated the utility of optical redox imaging (ORI) to monitor cellular metabolism and detect early metabolic response to cancer drugs.

Procedures

We performed ORI of human melanoma DB-1 cells in culture and DB-1 mouse xenografts to detect the redox response to lonidamine (LND) treatment.

Results

For cultured cells, LND treatment for 45 min significantly lowered NADH levels with no significant change in Fp, resulting in a significant increase in the Fp redox ratio (Fp/(NADH+Fp)); 3-h prolonged treatment led to a decrease in NADH and an increase in Fp and a more oxidized redox state compared to control. Significant decrease in the mitochondrial redox capacity of LND-treated cells was observed for the first time. For xenografts, 45-min LND treatment resulted in a significant reduction of NADH content, no significant changes in Fp content, and a trend of increase in the Fp redox ratio. Intratumor redox heterogeneity was observed in both control and LND-treated groups.

Conclusion

Our results support the utility of ORI for evaluating cellular metabolism and monitoring early metabolic response to cancer drugs.

Keywords

NADH Flavoproteins FAD Optical imaging Redox ratio Early detection Mitochondria DMSO 

Notes

Acknowledgements

This work was supported by the NIH Grants R01CA155348 (L.Z. Li), R01CA191207 (L.Z. Li), R01-CA129544 (J. Glickson), and R01CA172820 (J. Glickson). We would also like to thank Ms. Lily Moon for technical assistance with mouse xenografts.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11307_2018_1258_MOESM1_ESM.pdf (230 kb)
ESM 1 (PDF 230 kb)

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Copyright information

© World Molecular Imaging Society 2018

Authors and Affiliations

  1. 1.Department of RadiologyUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Department of Biochemistry and BiophysicsUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Institute of Translational Medicine and Therapeutics, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of Clinical SciencesTemple University School of MedicinePhiladelphiaUSA
  5. 5.Abramson Cancer CenterUniversity of PennsylvaniaPhiladelphiaUSA

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