Abstract
Positron emission tomography (PET) is a radiotracer imaging method that is increasingly used in both the clinical care of breast cancer patients and in translational breast cancer research. This review emphasizes current and future clinical applications of PET to breast cancer, and highlights some translational research using PET to elucidate the clinical biology of breast cancer. PET principles are reviewed, followed by a review of current applications of 18F-fluorodeoxyglucose (FDG) to clinical breast cancer care. Finally we review work done with other radiopharmaceuticals beyond FDG designed to image a number of aspects of breast cancer biology, emphasizing those most likely to enter clinical trials in the near future.
Similar content being viewed by others
Abbreviations
- CT:
-
computed tomography
- ER:
-
estrogen receptor
- FDG:
-
fluorodeoxyglucose
- ID:
-
injected dose
- MRI:
-
magnetic resonance imaging
- mCi:
-
millicuries (radioactivity unit)
- PET:
-
positron emission tomography
- PET/CT:
-
combined PET and CT on a single tomograph
- SPECT:
-
single photon emission computed tomography
- SUV:
-
standardized uptake value
References
Benard F, Turcotte E. Imaging in breast cancer: single-photon computed tomography and positron-emission tomography. Breast Cancer Res 2005;7(4):153–62.
Eubank WB, Mankoff DA. Evolving role of positron emission tomography in breast cancer imaging. Semin Nucl Med 2005;35(2):84–99.
Kelloff GJ, Hoffman JM, Johnson B, Scher HI, Siegel BA, Cheng EY, et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res 2005;11(8):2785–808.
Berger F, Gambhir SS. Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects: applications to breast cancer. Breast Cancer Res 2001;3(1):28–35.
Alessio AM, Kinahan PE, Cheng PM, Vesselle H, Karp JS. PET/CT scanner instrumentation, challenges, and solutions. Radiol Clin North Am 2004;42(6):1017–32 (vii).
Tewson T, Krohn K. PET radiopharmeceuticals: state-of-the-art and future prospects. Semin Nucl Med 1998;28:221–34.
Phelps M, Huang S, Hoffman E. Tomographic measurement of local cerebral glucose metabolic rate in humans with (18F)2-fluoro-2-deoxy-d-glucose: validation of method. Ann Neurol 1979;6(5):371.
Reivich M, Alavi A, Wolf A, Fowler J, Russell J, Arnett C, et al. Glucose metabolic rate kinetic model parameter determination in humans: the lumped constant and rate constants for [18F] fluorodeoxyglucose and [11C]deoxyglucose. J Cereb Blood Flow Metabol 1985;5:179–92.
Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, et al. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 1977;28:897–916.
Mankoff DA, Muzi M, Krohn KA. Quantitative positron emission tomography imaging to measure tumor response to therapy: what is the best method? Mol Imaging Biol 2003;5(5):281–5.
Warburg O. The metabolism of tumors. New York: Richard R. Smith; 1931.
Spence AM, Muzi M, Graham MM, O’Sullivan F, Krohn KA, Link JM, et al. Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: analysis of the FDG lumped constant. J Nucl Med 1998;39(3):440–8.
Bos R, van Der Hoeven JJ, van Der Wall E, van Der Groep P, van Diest PJ, Comans EF, et al. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 2002;20(2):379–87.
Avril N, Menzel M, Dose J, Schelling M, Weber W, Janicke F, et al. Glucose metabolism of breast cancer assessed by 18F-FDG PET: histologic and immunohistochemical tissue analysis. J Nucl Med 2001;42(1):9–16.
Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Charlop A, Lawton TJ, et al. Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy. J Nucl Med 2002;43(4):500–9.
Oshida M, Uno K, Suzuki M, Nagashima T, Hashimoto H, Yagata H, et al. Predicting the prognoses of breast carcimoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-d-glucose. Cancer 1998(1):2227–34.
Inoue T, Yutani K, Taguchi T, Tamaki Y, Shiba E, Noguchi S. Preoperative evaluation of prognosis in breast cancer patients by [(18)F]2-Deoxy-2-fluoro-d-glucose-positron emission tomography. J Cancer Res Clin Oncol 2004;130(5):273–8.
Avril N, Rose CA, Schelling M, Dose J, Kuhn W, Bense S, et al. Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. J Clin Oncol 2000;18(20):3495–502.
Lehman CD, Blume JD, Weatherall P, Thickman D, Hylton N, Warner E, et al. Screening women at high risk for breast cancer with mammography and magnetic resonance imaging. Cancer 2005;103(9):1898–905.
Adler LP, Weinberg IN, Bradbury MS, Levine EA, Lesko NM, Geisinger KR, et al. Method for combined FDG-PET and radiographic imaging of primary breast cancers. Breast J 2003;9(3):163–6.
Rosen EL, Turkington TG, Soo MS, Baker JA, Coleman RE. Detection of primary breast carcinoma with a dedicated, large-field-of-view FDG PET mammography device: initial experience. Radiology 2005;234(2):527–34.
Eubank WB, Mankoff DA. Current and future uses of positron emission tomography in breast cancer imaging. Semin Nucl Med 2004;34(3):224–40.
Wahl RL, Siegel BA, Coleman RE, Gatsonis CG. 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. J Clin Oncol 2004;22(2):277–85.
van der Hoeven JJ, Hoekstra OS, Comans EF, Pijpers R, Boom RP, van Geldere D, et al. Determinants of diagnostic performance of [F-18]fluorodeoxyglucose positron emission tomography for axillary staging in breast cancer. Ann Surg 2002;236(5):619–24.
Sugg SL, Ferguson DJ, Posner MC, Heimann R. Should internal mammary nodes be sampled in the sentinel lymph node era? Ann Surg Oncol 2000;7:188–92.
Schirrmeister H, Kuhn T, Guhlmann A, Santjohanser C, Horster T, Nussle K, et al. Fluorine-18 2-deoxy-2-fluoro-d-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures. Eur J Nucl Med 2001;28(3):351–8.
Bellon JR, Livingston RB, Eubank WB, Gralow JR, Ellis GK, Dunnwald LK, et al. Evaluation of the internal mammary lymph nodes by FDG-PET in locally advanced breast cancer (LABC). Am J Clin Oncol 2004;27(4):407–10.
Tran A, Pio BS, Khatibi B, Czernin J, Phelps ME, Silverman DH. 18F-FDG PET for staging breast cancer in patients with inner-quadrant versus outer-quadrant tumors: comparison with long-term clinical outcome. J Nucl Med 2005;46(9):1455–9.
Jones A, Bernstein V, Davis N, Bryce C, Wilson D, Mankoff D. Pilot feasibility study to assess the utility of PET scanning in the pre-operative evaluation of internal mammary nodes in breast cancer patients presenting with medial hemisphere tumors. Clin Positron Imaging 1999;2(6):331.
van der Hoeven JJ, Krak NC, Hoekstra OS, Comans EF, Boom RP, van Geldere D, et al. 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography in staging of locally advanced breast cancer. J Clin Oncol 2004;22(7):1253–9.
Eubank WB, Mankoff DA, Schmiedl UP, Winter TC, III, Fisher ER, Olshen AB, et al. Imaging of oncologic patients: benefit of combined CT and FDG PET in the diagnosis of malignancy. AJR Am J Roentgenol 1998;171(4):1103–10.
Hathaway PB, Mankoff DA, Maravilla KR, Austin-Seymour MM, Ellis GK, Gralow JR, et al. The value of combined FDG-PET and magnetic resonance imaging in the evaluation of suspected recurrent local-regional breast cancer: preliminary experience. Radiology 1999;210:807–14.
Ahmad A, Barrington S, Maisey M, Rubens RD. Use of positron emission tomography in evaluation of brachial plexopathy in breast cancer patients. Br J Cancer 1999;79(3–4):478–82.
Vansteenkiste JF. PET scan in the staging of non-small cell lung cancer. Lung Cancer 2003;42 (Suppl 1):S27–37.
Eubank WB, Mankoff DA, Takasugi J, Vesselle H, Eary JF, Shanley TJ, et al. 18fluorodeoxyglucose positron emission tomography to detect mediastinal or internal mammary metastases in breast cancer. J Clin Oncol 2001;19(15):3516–23.
Isasi CR, Moadel RM, Blaufox MD. A meta-analysis of FDG-PET for the evaluation of breast cancer recurrence and metastases. Breast Cancer Res Treat 2005;90(2):105–12.
Lonneux M, Borbath II, Berliere M, Kirkove C, Pauwels S. The place of whole-body PET FDG for the diagnosis of distant recurrence of breast cancer. Clin Positron Imaging 2000;3(2):45–9.
Vranjesevic D, Filmont JE, Meta J, Silverman DH, Phelps ME, Rao J, et al. Whole-body (18)F-FDG PET and conventional imaging for predicting outcome in previously treated breast cancer patients. J Nucl Med 2002;43(3):325–9.
Cook GJ, Houston S, Rubens R, Maisey MN, Fogelman I. Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic activity in osteoblastic and osteolytic lesions. J Clin Oncol 1998;16(10):3375–9.
Nakai T, Okuyama C, Kubota T, Yamada K, Ushijima Y, Taniike K, et al. Pitfalls of FDG-PET for the diagnosis of osteoblastic bone metastases in patients with breast cancer. Eur J Nucl Med Mol Imaging 2005.
Schirrmeister H, Guhlmann A, Kotzerke J, Santjohanser C, Kuhn T, Kreienberg R, et al. Early detection and accurate description of extent of metastatic bone disease in breast cancer with fluoride ion and positron emission tomography. J Clin Oncol 1999;17(8):2381–9.
Zangheri B, Messa C, Picchio M, Gianolli L, Landoni C, Fazio F. PET/CT and breast cancer. Eur J Nucl Med Mol Imaging 2004;31 (Suppl 1):S135–42.
Yap CS, Seltzer MA, Schiepers C, Gambhir SS, Rao J, Phelps ME, et al. Impact of whole-body 18F-FDG PET on staging and managing patients with breast cancer: the referring physician’s perspective. J Nucl Med 2001;42(9):1334–7.
Eubank WB, Mankoff D, Bhattacharya M, Gralow J, Linden H, Ellis G, et al. Impact of FDG PET on defining the extent of disease and on the treatment of patients with recurrent or metastatic breast cancer. AJR Am J Roentgenol 2004;183(2):479–86.
Biersack HJ, Bender H, Palmedo H. FDG-PET in monitoring therapy of breast cancer. Eur J Nucl Med Mol Imaging 2004;31 (Suppl 1):S112–7.
Wahl RL, Zasadny K, Helvie M, et al. Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. J Clin Oncol 1993;11:2101–11.
Mankoff DA, Dunnwald LK. Changes in glucose metabolism and blood flow following chemotherapy for breast cancer. PET Clinics 2006;1(1):71–82.
Schelling M, Avril N, Nahrig J, Kuhn W, Romer W, Sattler D, et al. Positron emission tomography using [18F] fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol 2000;18:1689–95.
Smith I, Welch A, Hutcheon A, Miller I, Payne S, Chilcott F, et al. Positron emission tomography using [18F]-fluorodeoxy-d-glucose to predict the pathologic response of breast cancer to primary chemotherapy. J Clin Oncol 2000;18:1676–88.
Wilson CBJH, Lammertsma AA, McKenzie CG, Sikora K, Jones T. Measurements of blood flow and exchanging water space in breast tumors using positron emission tomography: a rapid and non-invasive dynamic method. Cancer Research 1992;52:1592–97.
Dunnwald LK, Gralow JR, Ellis GK, Livingston RB, Linden HM, Lawton TJ, et al. Residual tumor uptake of [99mTc]-sestamibi after neoadjuvant chemotherapy for locally advanced breast carcinoma predicts survival. Cancer 2005;103(4):680–8.
Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Schubert EK, Tseng J, et al. Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy. J Nucl Med 2003;44(11):1806–14.
Tseng J, Dunnwald LK, Schubert EK, Link JM, Minoshima S, Muzi M, et al. 18F-FDG kinetics in locally advanced breast cancer: correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. J Nucl Med 2004;45(11):1829–37.
Gennari A, Donati S, Salvadori B, Giorgetti A, Salvadori PA, Sorace O, 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. Clin Breast Cancer 2000;1(2):156–61; discussion 162–3.
Dose Schwarz J, Bader M, Jenicke L, Hemminger G, Janicke F, Avril N. Early prediction of response to chemotherapy in metastatic breast cancer using sequential 18F-FDG PET. J Nucl Med 2005;46(7):1144–50.
Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 2001;19(11):2797–803.
Nielsen OS, Munro AJ, Tannock IF. Bone metastases: pathophysiology and management policy. J Clin Oncol 1991;9(3):509–24.
Stafford SE, Gralow JR, Schubert EK, Rinn KJ, Dunnwald LK, Livingston RB, et al. Use of serial FDG PET to measure the response of bone-dominant breast cancer to therapy. Acad Radiol 2002;9(8):913–21.
Tam SL, Gralow JR, Livingston RB, Linden HM, Ellis GK, Schubert EK, et al. Serial FDG-PET to monitor treatment of bone-dominant metastatic breast cancer predicts time to progression (TTP). Proceedings of ASCO, J Clin Oncol 2005;23(16S):633.
Kaklamani V, O’Regan RM. New targeted therapies in breast cancer. Semin Oncol 2004;31(2 Suppl 4):20–5.
Katzenellenbogen JA, Welch MJ, Dehdashti F. The development of estrogen and progestin radiopharmaceuticals for imaging breast cancer. Anticancer Res 1997;17:1573–76.
Gonzalez Trotter DE, Manjeshwar RM, Doss M, Shaller C, Robinson MK, Tandon R, et al. Quantitation of small-animal (124)I activity distributions using a clinical PET/CT scanner. J Nucl Med 2004;45(7):1237–44.
Zasadny KR, Tatsumi M, Wahl RL. FDG metabolism and uptake versus blood flow in women with untreated primary breast cancers. Eur J Nucl Med Mol Imaging 2003;30(2):274–80.
Haubner R, Wester HJ, Burkhart F, Senekowitsch-Schmidtke R, Weber W, Goodman SL, et al. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med 2001;42(2):326–36.
Zheng QH, Fei X, Liu X, Wang JQ, Bin Sun H, Mock BH, et al. Synthesis and preliminary biological evaluation of MMP inhibitor radiotracers [11C]methyl-halo-CGS 27023A analogs, new potential PET breast cancer imaging agents. Nucl Med Biol 2002;29(7):761–70.
Sledge GJ, McGuire W. Steroid hormone receptors in human breast cancer. Adv Cancer Res 1983;38:61–75.
Mintun MA, Welch MJ, Siegel BA, Mathias CJ, Brodack JW, McGuire AH, et al. Breast cancer: PET imaging of estrogen receptors. Radiology 1988;169(1):45–8.
Dehdashti F, Mortimer JE, Siegel BA, Griffeth LK, Bonasera TJ, Fusselman MJ, et al. Positron tomographic assessment of estrogen receptors in breast cancer: a comparison with FDG-PET and in vitro receptor assays. J Nucl Med 1995;36:1766–74.
Mankoff DA, Peterson LM, Tewson TJ, Link JM, Gralow JR, Graham MM, et al. [18F]fluoroestradiol radiation dosimetry in human PET studies. J Nucl Med 2001;42(4):679–84.
Linden HM, Stekhova SA, Link JM, Gralow JR, Livingston RB, Ellis GK, et al. Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment. J Clin Oncol 2006;24:2793–9.
Aboagye EO, Price PM. Use of positron emission tomography in anticancer drug development. Invest New Drugs 2003;21(2):169–81.
Sutherland R. Tumor hypoxia and gene expression. Acta Oncologica 1998;37:567–74.
Vaupel P, Hockel M. Oxygenation status of breast cancer: the Mainz experience. In: Vaupel, Kelleher, editors. Tumor hypoxia. Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH; 1999. pp. 1–12.
Rajendran JG, Mankoff DA, O’Sullivan F, Peterson LM, Schwartz DL, Conrad EU, et al. Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging. Clin Cancer Res 2004;10(7):2245–52.
Rajendran JG, Krohn KA. Imaging hypoxia and angiogenesis in tumors. Radiol Clin North Am 2005;43(1):169–87.
Dehdashti F, Grigsby PW, Mintun MA, Lewis JS, Siegel BA, Welch MJ. Assessing tumor hypoxia in cervical cancer by positron emission tomography with 60Cu-ATSM: relationship to therapeutic response-a preliminary report. Int J Radiat Oncol Biol Phys 2003;55(5):1233–8.
Kaye SB. Multidrug resistance: clinical relevance in solid tumours and strategies for circumvention. Curr Opin Oncol 1998;10 (Suppl 1):S15–9.
Piwnica-Worms D, Chiu ML, Budding M, Kronauge JF, Kramer RA, Croop JM. Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex. Cancer Research 1993;53:977–84.
Ciarmiello A, Vecchio SD, Silvestro P, Potenta M, Carriero M, Thomas R, et al. Tumor clearance of technetium 99 m-sestamibi as a predictor of response to neoadjuvant chemotherapy for locally advanced breast cancer. J Clin Oncol 1998;16(5):1677–83.
Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Schubert EK, Charlop AW, et al. [Tc-99m]-sestamibi uptake and washout in locally advanced breast cancer are correlated with tumor blood flow. Nucl Med Biol 2002;29(7):719–27.
Hendrikse NH, de Vries EG, Eriks-Fluks L, van der Graaf WT, Hospers GA, Willemsen AT, et al. A new in vivo method to study P-glycoprotein transport in tumors and the blood-brain barrier. Cancer Res 1999;59(10):2411–6.
Sasongko L, Link JM, Muzi M, Mankoff DA, Yang X, Collier AC, et al. Imaging P-glycoprotein transport activity at the human blood-brain barrier with positron emission tomography. Clin Pharmacol Ther 2005;77(6):503–14.
Kurziel KA, Kieswetter do, Carson RE, Eckelman WC, Herscovitch P. Biodistribution, radiation dose estimates, and in vivo P-gp modulation studies of 18F-paclitaxel in nonhuman primates. J Nucl Med 2003;44:1330–39.
Cleaver JE. Thymidine metabolism and cell kinetics. Frontiers Biol 1967;6:43–100.
Mankoff DA, Shields AF, Krohn KA. PET imaging of cellular proliferation. Radiol Clin North Am 2005;43(1):153–67.
Grierson JR, Shileds AF. Radiosymthesis of 3′-deoxy-3′-[F-18]-fluorothymidine: [F-18]-FLT for imaging of cellular proliferation in vivo. Nucl Med Biol 2000;27:143–56.
Smyczek-Gargya B, Fersis N, Dittmann H, Vogel U, Reischl G, Machulla HJ, et al. PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study. Eur J Nucl Med Mol Imaging 2004;31(5):720–4.
Pio BS, Park CK, Satyamurthy N, Czernin J, Phelps ME, Silverman DH. PET with fluoro-L-thmyidine allows early prediction of breast cancer rresponse to chemotherapy. J Nucl Med 2003;44(5):76P.
Hockenbery D. Defining apoptosis. Am J Pathol 1995;146(1):16–9.
Blankenberg F, Katsikis P, Tait J, Davis R, Naumovski L, Ohtsuki K, et al. Imaging of apoptosis (programmed cell death) with 99mTc annexin V. J Nucl Med 1999;40:184–91.
Yagle KJ, Eary JF, Tait JF, Grierson JR, Link JM, Lewellen B, et al. Evaluation of 18F-annexin V as a PET imaging agent in an animal model of apoptosis. J Nucl Med 2005;46(4):658–66.
Acknowledgments
This work was supported by NIH Grants R01CA42045, RO1CA72064, RO1CA90771, and S10RR177229. The authors wish to acknowledge Ms. Erin Schubert for help with figure reproduction.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mankoff, D.A., Eubank, W.B. Current and Future Use of Positron Emission Tomography (PET) in Breast Cancer. J Mammary Gland Biol Neoplasia 11, 125–136 (2006). https://doi.org/10.1007/s10911-006-9019-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10911-006-9019-z