title: Hypoxia in melanoma: using optical spectroscopy and EF5 to assess tumor oxygenation before and during regional chemotherapy for melanoma.
abstract: BACKGROUND
  There is increasing evidence that tumor hypoxia plays a significant role in the chemoresistance of melanoma, but to our knowledge, real-time tumor oxygenation during isolated limb infusion (ILI) has not been studied. We sought to demonstrate the feasibility of measuring real-time alterations in tissue oxygenation.
  
  
  METHODS
  Consecutive patients with histologically confirmed in-transit melanoma were enrolled onto a prospective single-arm pilot study and administered the hypoxia marker drug EF5. All patients were treated with ILI. Optical spectroscopy readings were obtained at three locations: two discrete target lesions and one normal skin control. Measurements were taken at 11 predefined time points during ILI.
  
  
  RESULTS
  A total of six patients were enrolled onto this pilot study. Intratumor and normal skin optical spectroscopy readings were found to have discrete inflection points throughout the duration of therapy, corresponding with established time points. Baseline hypoxia as measured by both optical spectroscopy and EF5 immunofluorescence was variable, but on the basis of optical spectra, tumors appeared to become more hypoxic compared to normal skin after tourniquet application. The optical hypoxia signature was variable between patients while hemoglobin absorption increased.
  
  
  CONCLUSIONS
  To our knowledge, this is the first use of real-time optical spectroscopy to evaluate oxygenation and perfusion within melanoma lesions during regional chemotherapy. We report our development of this new noninvasive means of assessing tumor vascular function, which has the potential to be a powerful tool for noninvasive examination of the melanoma tumor microenvironment.
authors: Department of Surgery, Duke University Medical Center, Durham, NC, USA, paul.speicher@duke.edu.
authors: Paul J
authors: PJ
authors: Speicher
authors: Georgia M
authors: GM
authors: Beasley
authors: Betty
authors: B
authors: Jiang
authors: Michael E
authors: ME
authors: Lidsky
authors: Gregory M
authors: GM
authors: Palmer
authors: Peter M
authors: PM
authors: Scarbrough
authors: Paul J
authors: PJ
authors: Mosca
authors: Mark W
authors: MW
authors: Dewhirst
authors: Douglas S
authors: DS
authors: Tyler
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D017341:Etanidazole / Q000031:analogs & derivatives*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D000860:Hypoxia / Q000175:diagnosis* / Q000378:metabolism; D007202:Indicators and Reagents; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D011446:Prospective Studies; D005466:Fluorocarbons
chemical_list: D018906:Antineoplastic Agents, Alkylating; D017341:Etanidazole; D006845:Hydrocarbons, Fluorinated; D007202:Indicators and Reagents; D008558:Melphalan; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons
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