Early changes in 2-deoxy-2-[18F]fluoro-D-glucose metabolism in squamous-cell carcinoma during chemotherapy in vivo and in vitro.

AIM The aim of this study was to investigate early changes in uptake of 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) in vivo and in vitro in a squamous-cell carcinoma (SCC) cell line originating from a human head and neck SCC during cytotoxic therapy with respect to metabolism in tumor cells and in surrounding stromal tissue. MATERIALS AND METHODS In 60 nude mice with xenografted SCC, 50 animals were treated with cisplatin. Early changes in the tumor FDG uptake following therapy were evaluated sequentially with phosphor imaging. Using this technique, areas with focal hypermetabolism were detected. The cells creating the focal hypermetabolism were then identified histopathologically on the corresponding sections. In addition, early FDG uptake versus the number of viable tumor cells was measured in vitro following cisplatin treatment. RESULTS An early transient increase in FDG uptake in tumor cells was seen on day 1 in treated tumors, followed by a rapid decrease confirmed by subsequent tumor regression. This metabolic flare was present in all treated tumors but not in the controls. In vitro, an increase in FDG uptake per cell was observed. CONCLUSIONS Our results provide new insights into the early metabolic changes in squamous-cell carcinomas subjected to cytotoxic therapy and thus contribute to the discussion on the feasibility of early predictive PET studies.

[1]  M. Schwaiger,et al.  Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  P. Grigsby,et al.  18-F-fluorodeoxyglucose-positron emission tomography evaluation of early metabolic response during radiation therapy for cervical cancer. , 2008, International journal of radiation oncology, biology, physics.

[3]  E. Croteau,et al.  A Small Animal Positron Emission Tomography Study of the Effect of Chemotherapy and Hormonal Therapy on the Uptake of 2-Deoxy-2-[F-18]fluoro-d-glucose in Murine Models of Breast Cancer , 2007, Molecular Imaging and Biology.

[4]  S. Ben-Haim,et al.  18F-FDG PET and PET/CT in the Evaluation of Cancer Treatment Response* , 2008, Journal of Nuclear Medicine.

[5]  T Ido,et al.  Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  O. Prante,et al.  Uptake of [18F]fluorodeoxyglucose in human monocyte-macrophages in vitro , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[7]  Johan Wennerberg,et al.  2-Deoxy-2-[18F] fluoro-D-glucose uptake and correlation to intratumoral heterogeneity. , 2007, Anticancer research.

[8]  18FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response , 2006, British Journal of Cancer.

[9]  J. Nährig,et al.  Positron emission tomography using [(18)F]Fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  A. Alavi,et al.  Defining co-related parameters between ‘metabolic’ flare and ‘clinical’, ‘biochemical’, and ‘osteoblastic’ flare and establishing guidelines for assessing response to treatment in cancer , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[11]  Patrick Dupont,et al.  [18F]FDG PET monitoring of tumour response to chemotherapy: does [18F]FDG uptake correlate with the viable tumour cell fraction? , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[12]  J. Wennerberg Changes in growth pattern of human squamous‐cell carcinomas of the head and neck during serial passages in nude mice , 1984, International journal of cancer.

[13]  W. Oyen,et al.  Predictive and prognostic value of FDG‐PET in nonsmall‐cell lung cancer , 2007, Cancer.

[14]  Wolfgang A. Weber,et al.  Monitoring chemotherapy and radiotherapy of solid tumors , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[15]  Å. Borg,et al.  p53 mutation and cyclin D1 amplification correlate with cisplatin sensitivity in xenografted human squamous cell carcinomas from head and neck , 2006, Acta oncologica.

[16]  Wolfgang A Weber,et al.  Use of PET for monitoring cancer therapy and for predicting outcome. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  M. Welch,et al.  Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  P. Vaupel,et al.  Hypoxia in cancer: significance and impact on clinical outcome , 2007, Cancer and Metastasis Reviews.

[19]  T. Hickish,et al.  Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: correlation with tumor response to fluorouracil. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  Martin Hutchings,et al.  FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. , 2006, Blood.