Optical molecular imaging detects changes in extracellular pH with the development of head and neck cancer

Melissa N. Loja, Zhen Luo, D. Greg Farwell, Quang C. Luu, Paul J. Donald, Deborah Amott, Anh Q. Truong, Regina F Gandour-Edwards, N. Nitin

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Noninvasive localized measurement of extracellular pH in cancer tissues can have a significant impact on the management of cancer. Despite its significance, there are limited approaches for rapid and noninvasive measurement of local pH in a clinical environment. In this study, we demonstrate the potential of noninvasive topical delivery of Alexa-647 labeled pHLIP (pH responsive peptide conjugated with Alexa Fluor® 647) to image changes in extracellular pH associated with head and neck squamous cell carcinoma using widefield and high resolution imaging. We report a series of preclinical analyses to evaluate the optical contrast achieved after topical delivery of Alexa-647 labeled pHLIP in intact fresh human tissue specimens using widefield and high-resolution fluorescence imaging. Using topical delivery, Alexa-647 labeled pHLIP can be rapidly delivered throughout the epithelium of intact tissues with a depth exceeding 700 μm. Following labeling with Alexa-647 labeled pHLIP, the mean fluorescent contrast increased four to eight fold higher in clinically abnormal tissues as compared to paired clinically normal biopsies. Furthermore, the imaging approach showed significant differences in fluorescence contrast between the cancer and the normal biopsies across diverse patients and different anatomical sites (unpaired comparison). The fluorescence contrast differences between clinically abnormal and normal tissues were in agreement with the pathologic evaluation. Topical application of fluorescently labeled pHLIP can detect and differentiate normal from cancerous tissues using both widefield and high resolution imaging. This technology will provide an effective tool to assess tumor margins during surgery and improve detection and prognosis of head and neck cancer. What's new? When tumor cells become hypoxic, they release acidic metabolites. An acidic microenvironment is associated with increased metastasis, as well as resistance to treatment. In this study, the authors asked whether an optical-imaging technique could detect altered pH in biopsies from patients with head and neck cancer. They were able to detect and differentiate cancerous from normal tissues. This technology may provide an effective tool to assess tumor margins during surgery, and to improve detection and prognosis of head and neck cancers.

Original languageEnglish (US)
Pages (from-to)1613-1623
Number of pages11
JournalInternational Journal of Cancer
Volume132
Issue number7
DOIs
StatePublished - Apr 1 2013

Fingerprint

Molecular Imaging
Optical Imaging
Head and Neck Neoplasms
Neoplasms
Biopsy
Fluorescence
Technology
Epithelium
Neoplasm Metastasis
Peptides

Keywords

  • confocal microscopy
  • head and neck cancer
  • optical widefield imaging
  • pH imaging
  • topical delivery

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Loja, M. N., Luo, Z., Greg Farwell, D., Luu, Q. C., Donald, P. J., Amott, D., ... Nitin, N. (2013). Optical molecular imaging detects changes in extracellular pH with the development of head and neck cancer. International Journal of Cancer, 132(7), 1613-1623. https://doi.org/10.1002/ijc.27837

Optical molecular imaging detects changes in extracellular pH with the development of head and neck cancer. / Loja, Melissa N.; Luo, Zhen; Greg Farwell, D.; Luu, Quang C.; Donald, Paul J.; Amott, Deborah; Truong, Anh Q.; Gandour-Edwards, Regina F; Nitin, N.

In: International Journal of Cancer, Vol. 132, No. 7, 01.04.2013, p. 1613-1623.

Research output: Contribution to journalArticle

Loja, MN, Luo, Z, Greg Farwell, D, Luu, QC, Donald, PJ, Amott, D, Truong, AQ, Gandour-Edwards, RF & Nitin, N 2013, 'Optical molecular imaging detects changes in extracellular pH with the development of head and neck cancer', International Journal of Cancer, vol. 132, no. 7, pp. 1613-1623. https://doi.org/10.1002/ijc.27837
Loja, Melissa N. ; Luo, Zhen ; Greg Farwell, D. ; Luu, Quang C. ; Donald, Paul J. ; Amott, Deborah ; Truong, Anh Q. ; Gandour-Edwards, Regina F ; Nitin, N. / Optical molecular imaging detects changes in extracellular pH with the development of head and neck cancer. In: International Journal of Cancer. 2013 ; Vol. 132, No. 7. pp. 1613-1623.
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