Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography

Reinhard Bos, Jacobus J M van Der Hoeven, Elsken van Der Wall, Petra van Der Groep, Paul J van Diest, Emile F I Comans, Urvi Joshi, Gregg L Semenza, Otto S Hoekstra, Adriaan A Lammertsma, Carla F M Molthoff

Research output: Contribution to journalArticleAcademicpeer-review


PURPOSE: Variable uptake of the glucose analog (18)fluorodeoxyglucose (FDG) has been noticed in positron emission tomography (PET) studies of breast cancer patients, with low uptake occurring especially in lobular cancer. At present, no satisfactory biologic explanation exists for this phenomenon. This study compared (18)FDG uptake in vivo with biomarkers expected to be involved in the underlying biologic mechanisms.

PATIENTS AND METHODS: Preoperative (18)FDG-PET scans were performed in 55 patients. (18)FDG activity was assessed visually by three observers using a four-point score. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut-1); Hexokinase (HK) I, II, and III; macrophages; hypoxia-inducible factor-1-alfa (HIF-1alpha); vascular endothelial growth factor (VEGF(165)); and microvessels. Mitotic activity index (MAI), amount of necrosis, number of lymphocytes, and tumor cells/volume were assessed.

RESULTS: There were positive correlations between (18)FDG uptake and Glut-1 expression (P <.001), MAI (P =.001), amount of necrosis (P =.010), number of tumor cells/volume (P =.009), expression of HK I (P =.019), number of lymphocytes (P =.032), and microvessel density (r =.373; P =.005). HIF-1alpha, VEGF(165), HK II, HK III, and macrophages showed no univariate correlation with (18)FDG. In logistic regression, however, HIF-1alpha and HK II added value to MAI and Glut-1.

CONCLUSION: (18)FDG uptake in breast cancer is a function of microvasculature for delivering nutrients, Glut-1 for transportation of (18)FDG into the cell, HK for entering (18)FDG into glycolysis, number of tumor cells/volume, proliferation rate (also reflected in necrosis), number of lymphocytes (not macrophages), and HIF-1alpha for upregulating Glut-1. Together, these features explain why breast cancers vary in (18)FDG uptake and elucidate the low uptake in lobular breast cancer.

Original languageEnglish
Pages (from-to)379-87
Number of pages9
JournalJournal of Clinical Oncology
Issue number2
Publication statusPublished - 15 Jan 2002


  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms
  • DNA-Binding Proteins
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunohistochemistry
  • Lymphocytes
  • Microcirculation
  • Middle Aged
  • Monosaccharide Transport Proteins
  • Necrosis
  • Nuclear Proteins
  • Radiopharmaceuticals
  • Regional Blood Flow
  • Tomography, Emission-Computed
  • Transcription Factors


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