FDG-PET and beyond: molecular breast cancer imaging.

Positron emission tomography (PET) scanning has gained widespread acceptance for the diagnosis, staging, and management of a variety of malignancies, including breast cancer. This has heralded an exciting new era of molecular imaging research of which using FDG as the primary PET tracer is only the beginning. The fundamental strength of PET over conventional imaging is the ability to convey functional information that even the most exquisitely detailed anatomic image cannot provide. As the standard PET radiotracer in current clinical use, FDG is a glucose analog that is taken up by cells in proportion to their rate of glucose metabolism. The increased glycolytic rate and glucose avidity of malignant cells in comparison to normal tissue is the basis of the ability of FDG-PET imaging to accurately differentiate cancer from benign tissue irregardless of morphology. The level or intensity of FDG uptake on PET is semiquantified and reported as the standardized uptake value (SUV). A multitude of new PET tracers are under development, many of which are aimed at targeting cellular processes that are more specific than glucose metabolism. In relation to breast cancer, these tracers include thymidine analogs such as [F-18]fluoro-L-thymidine (FLT) that target DNA replication as a measure of cell proliferation, annexin V derivatives that evaluate apoptosis, estrogen receptor (ER) tracers such as 16 -[F-18]fluoroestradiol-17 (FES), and engineered antibody fragments that directly target HER-2/neu receptors. In addition to new tracers, scanner technology is also rapidly evolving. Chief among these is the advent of the dual modality PET/CT scanner, which at the very least increases patient convenience by permitting PET and computed tomography (CT) imaging in a single appointment. But perhaps more importantly, initial studies indicate that the sum of the two modalities is better than either used separately and also may be an extremely useful tool in preradiation therapy planning. Other new scanning devices are also being developed, including small gantry PET scanners designed specifically for breast imaging, and handheld PET probes for direct intraoperative localization of tracer-avid tumor foci.

[1]  Sanjiv Sam Gambhir,et al.  Positron emission tomography in diagnosis and management of invasive breast cancer: current status and future perspectives. , 2003, Clinical breast cancer.

[2]  C. Kao,et al.  Comparison and discrepancy of 18F-2-deoxyglucose positron emission tomography and Tc-99m MDP bone scan to detect bone metastases. , 2000, Anticancer research.

[3]  Barry A. Siegel,et al.  Prospective multicenter study of axillary nodal staging by positron emission tomography in breast cancer: a report of the staging breast cancer with PET Study Group. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  J C Rosenwald,et al.  CT and (18)F-deoxyglucose (FDG) image fusion for optimization of conformal radiotherapy of lung cancers. , 2001, International journal of radiation oncology, biology, physics.

[5]  H. Moch,et al.  Is positron emission tomography an accurate non-invasive alternative to sentinel lymph node biopsy in breast cancer patients? , 2003, Journal of the National Cancer Institute.

[6]  N. Cascinelli,et al.  Axillary lymph node staging in breast cancer by 2-fluoro-2-deoxy-D-glucose-positron emission tomography: clinical evaluation and alternative management. , 2001, Journal of the National Cancer Institute.

[7]  S. Gambhir Molecular imaging of cancer with positron emission tomography , 2002, Nature Reviews Cancer.

[8]  J. Carreras,et al.  Early diagnosis of recurrent breast cancer with FDG-PET in patients with progressive elevation of serum tumor markers. , 2002, The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology.

[9]  A. Kortt,et al.  Dimeric and trimeric antibodies: high avidity scFvs for cancer targeting. , 2001, Biomolecular engineering.

[10]  V. Lowe,et al.  Positron emission tomography and sentinel lymph node dissection in breast cancer. , 2002, Clinical breast cancer.

[11]  J. Bergh,et al.  Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: a method for early therapy evaluation? , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  R. Sutherland,et al.  Effects of oestrogens on cell proliferation and cell cycle kinetics. A hypothesis on the cell cycle effects of antioestrogens. , 1983, European journal of cancer & clinical oncology.

[13]  D. Mankoff,et al.  Evaluation of the Internal Mammary Lymph Nodes by FDG-PET in Locally Advanced Breast Cancer (LABC) , 2004, American journal of clinical oncology.

[14]  J L Sunshine,et al.  Evaluation of breast masses and axillary lymph nodes with [F-18] 2-deoxy-2-fluoro-D-glucose PET. , 1993, Radiology.

[15]  Gerald Reischl,et al.  PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[16]  S R Cherry,et al.  Design and evaluation of an LSO PET detector for breast cancer imaging. , 2000, Medical physics.

[17]  S. Yang,et al.  Comparing whole body 18F-2-deoxyglucose positron emission tomography and technetium-99m methylene diphosphonate bone scan to detect bone metastases in patients with breast cancer , 2002, Journal of Cancer Research and Clinical Oncology.

[18]  M. Greco,et al.  Prospective evaluation of fluorine-18-FDG PET in presurgical staging of the axilla in breast cancer. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[19]  A. Lammertsma,et al.  Determinants of Diagnostic Performance Of [F-18]Fluorodeoxyglucose Positron Emission Tomography for Axillary Staging in Breast Cancer , 2002, Annals of surgery.

[20]  Claudio Landoni,et al.  PET/CT and breast cancer , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[21]  Mark Muzi,et al.  Positron emission tomography imaging of brain tumors. , 2003, Neuroimaging clinics of North America.

[22]  C. Kao,et al.  Fluorine-18 FDG-PET in Detecting Local Recurrence and Distant Metastases in Breast Cancer—Taiwanese Experiences , 2002, Cancer investigation.

[23]  Michael J. Welch,et al.  Positron emission tomographic assessment of ”metabolic flare” to predict response of metastatic breast cancer to antiestrogen therapy , 1999, European Journal of Nuclear Medicine.

[24]  Cyrill Burger,et al.  Radiation treatment planning with an integrated positron emission and computer tomography (PET/CT): a feasibility study. , 2003, International journal of radiation oncology, biology, physics.

[25]  V. Bettinardi,et al.  Value of integrated PET/CT for lesion localisation in cancer patients: a comparative study , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[26]  R. Sutherland,et al.  Tamoxifen stimulation of human breast cancer cell proliferation in vitro: a possible model for tamoxifen tumour flare. , 1984, European journal of cancer & clinical oncology.

[27]  L. Adler,et al.  Axillary lymph node metastases: screening with [F-18]2-deoxy-2-fluoro-D-glucose (FDG) PET. , 1997, Radiology.

[28]  R L Wahl,et al.  Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  Robert B Livingston,et al.  Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy. , 2002, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[30]  M. Mintun,et al.  Positron Tomographic Assessment of 16α-[18F] Fluoro-17β-Estradiol Uptake in Metastatic Breast Carcinoma , 1991 .

[31]  M. Schwaiger,et al.  Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  A. Wu,et al.  Designer genes: recombinant antibody fragments for biological imaging. , 2000, The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology.

[33]  M. Tatsumi,et al.  Comparison of FDG-PET with MIBI-SPECT in the detection of breast cancer and axillary lymph node metastasis. , 2000, Journal of computer assisted tomography.

[34]  P F Sharp,et al.  Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  P. Sharp,et al.  Staging of the axilla in breast cancer: accurate in vivo assessment using positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose. , 1998, Annals of surgery.

[36]  X. Setoain,et al.  99mTc-MDP bone scintigraphy and 18F-FDG positron emission tomography in lung and prostate cancer patients: different affinity between lytic and sclerotic bone metastases , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[37]  Rainer Linke,et al.  18F-FDG PET and 99mTc-sestamibi scintimammography for monitoring breast cancer response to neoadjuvant chemotherapy: a comparative study , 2001, European Journal of Nuclear Medicine.

[38]  A. Pecking,et al.  Detection of occult disease in breast cancer using fluorodeoxyglucose camera-based positron emission tomography. , 2001, Clinical breast cancer.

[39]  H. Schirrmeister,et al.  Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures , 2001, European Journal of Nuclear Medicine.

[40]  D. Mankoff,et al.  18fluorodeoxyglucose positron emission tomography to detect mediastinal or internal mammary metastases in breast cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  David J. Yang,et al.  Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[42]  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.

[43]  Michael E Phelps,et al.  Relationship between 18F-FDG uptake and breast density in women with normal breast tissue. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[44]  Pauwels,et al.  The Place of Whole-Body PET FDG for the Diagnosis of Distant Recurrence of Breast Cancer. , 2000, Clinical positron imaging : official journal of the Institute for Clinical P.E.T.

[45]  H. Biersack,et al.  Comparison of fluorine-18 fluorodeoxyglucose positron emission tomography and technetium-99m methoxyisobutylisonitrile scintimammography in the detection of breast tumours , 1997, European Journal of Nuclear Medicine.

[46]  D. Mankoff,et al.  Use of serial FDG PET to measure the response of bone-dominant breast cancer to therapy. , 2002, Academic radiology.

[47]  S. Yasuda,et al.  Whole body PET for the evaluation of bony metastases in patients with breast cancer: comparison with 99Tcm-MDP bone scintigraphy , 2001, Nuclear medicine communications.

[48]  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.

[49]  H. Moch,et al.  Selective Axillary Surgery in Breast Cancer Patients Based on Positron Emission Tomography with 18F-Fluoro-2-Deoxy-D-Glucose: not Yet! , 2004, Breast Cancer Research and Treatment.

[50]  P A Salvadori,et al.  Role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early assessment of response to chemotherapy in metastatic breast cancer patients. , 2000, Clinical breast cancer.

[51]  C. Goldsmith,et al.  A Prospective Evaluation of Positron Emission Tomography Scanning, Sentinel Lymph Node Biopsy, and Standard Axillary Dissection for Axillary Staging in Patients with Early Stage Breast Cancer , 2004, Annals of Surgical Oncology.