Abstract
Purpose
The precise determination of energy metabolites is challenged by the heterogeneity of their distribution, their rapid changes after surgical resection and the architectural complexity of malignancies. Induced metabolic bioluminescence imaging (imBI) allows to determine energy metabolites in tissue sections and to co-localize these with histological structures based on consecutive sections stained with HE. In this prospective pilot study patients with suspected advanced ovarian cancer (OC) were enrolled to prove the feasibility of imBI.
Methods
During surgery, suspicious peritoneal metastases were resected and transferred in liquid nitrogen within 30 s. ATP, glucose and lactate concentrations were measured. Furthermore, the expression of monocarboxylate transporters MCT1 and MCT4 was determined by immunofluorescence staining.
Results
16 patients were screened, 12 entered the study. Final histological assessment revealed ten malignant and two benign peritoneal lesions. In all 12 cases high concentrations of ATP suggested that energy metabolism was not altered by the surgical and transport procedures (mean 0.56 μmol/g, range 0.24–1.21 μmol/g). The mean concentration of glucose was 1.95 μmol/g (range 0.58–4.71 μmol/g). The concentration of lactate was drastically higher in the ten OC cases (mean 24.79 μmol/g, range 17.51–37.16 μmol/g) compared to the benign samples (mean 5.98 μmol/g, range 5.43–6.54 μmol/g). Lactate concentrations seem to correlate with MCT1 (spearman rank correlation ρ = 0.624, 0.05 > p > 0.025), but not with MCT4 (spearman rank correlation ρ = 0.018, p > 0.1).
Conclusions
ImBI is feasible in peritoneal metastases of OC and encourages further effort to elucidate the role of glucose, lactate, MCT1 and MCT4 in OC.
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Acknowledgement
Parts of these results were presented on the annual meeting of the American society of clinical oncology (ASCO) 2016.
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All authors declare that they have no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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M. J. Battista and K. Goetze contributed equally and share first authorship.
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Battista, M.J., Goetze, K., Schmidt, M. et al. Feasibility of induced metabolic bioluminescence imaging in advanced ovarian cancer patients: first results of a pilot study. J Cancer Res Clin Oncol 142, 1909–1916 (2016). https://doi.org/10.1007/s00432-016-2200-x
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DOI: https://doi.org/10.1007/s00432-016-2200-x