Skip to main content
SpringerLink
Log in

A new dimension of FDG-PET interpretation: assessment of tumor biology

  • Review Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

18F-Fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) is increasingly being used for the evaluation of several malignancies. Key to the correct interpretation of oncological FDG-PET studies is awareness of the concept that the degree of FDG uptake reflects the biology of the tumor in many cancers. More specifically, cancers with high FDG uptake are often histologically and clinically more aggressive than those with low or no FDG uptake. Therefore, although a negative FDG-PET scan in a patient with a cancer that has a size above the spatial resolution of PET may be interpreted as false-negative in terms of tumor detectability, it should in fact be regarded as true-negative from the view-point of tumor biology. This nonsystematic review will give examples of several major cancers in which the relationship between FDG avidity and tumor biology is applicable, and emphasizes the need to reconsider the definition of a “false-negative” FDG-PET scan in clinical oncology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Basu S, Alavi A. Unparalleled contribution of 18F-FDG PET to medicine over 3 decades. J Nucl Med. 2008;49:17N–21N, 37N.

    Article  PubMed  Google Scholar 

  2. Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology. 2004;231:305–32.

    Article  PubMed  Google Scholar 

  3. Gillies RJ, Robey I, Gatenby RA. Causes and consequences of increased glucose metabolism of cancers. J Nucl Med. 2008;49 Suppl 2:24S–42S.

    Article  PubMed  CAS  Google Scholar 

  4. Fletcher JW, Djulbegovic B, Soares HP, Siegel BA, Lowe VJ, Lyman GH, et al. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med. 2008;49:480–508.

    Article  PubMed  Google Scholar 

  5. Jadvar H, Alavi A, Gambhir SS. 18F-FDG uptake in lung, breast, and colon cancers: molecular biology correlates and disease characterization. J Nucl Med. 2009;50:1820–7.

    Article  PubMed  Google Scholar 

  6. Basu S, Kumar R, Mavi A, Alavi A. Exploring tumor biology with fluorodeoxyglucose-positron emission tomography imaging in breast carcinoma. PET Clin. 2009;4:381–9.

    Article  Google Scholar 

  7. Samson DJ, Flamm CR, Pisano ED, Aronson N. Should FDG PET be used to decide whether a patient with an abnormal mammogram or breast finding at physical examination should undergo biopsy? Acad Radiol. 2002;9:773–83.

    Article  PubMed  Google Scholar 

  8. Kumar R, Chauhan A, Zhuang H, Chandra P, Schnall M, Alavi A. Clinicopathologic factors associated with false negative FDG-PET in primary breast cancer. Breast Cancer Res Treat. 2006;98:267–74.

    Article  PubMed  Google Scholar 

  9. Basu S, Chen W, Tchou J, Mavi A, Cermik T, Czerniecki B, et al. Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization. Cancer. 2008;112:995–1000.

    Article  PubMed  CAS  Google Scholar 

  10. Jaskowiak CJ, Bianco JA, Perlman SB, Fine JP. Influence of reconstruction iterations on 18F-FDG PET/CT standardized uptake values. J Nucl Med. 2005;46:424–8.

    PubMed  Google Scholar 

  11. Wang W, Larson SM, Fazzari M, Tickoo SK, Kolbert K, Sgouros G, et al. Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab. 2000;85:1107–13.

    Article  PubMed  CAS  Google Scholar 

  12. Robbins RJ, Wan Q, Grewal RK, Reibke R, Gonen M, Strauss HW, et al. Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning. J Clin Endocrinol Metab. 2006;91:498–505.

    Article  PubMed  CAS  Google Scholar 

  13. Weiler-Sagie M, Bushelev O, Epelbaum R, Dann EJ, Haim N, Avivi I, et al. (18)F-FDG avidity in lymphoma readdressed: a study of 766 patients. J Nucl Med. 2010;51:25–30.

    Article  PubMed  Google Scholar 

  14. Schöder H, Noy A, Gönen M, Weng L, Green D, Erdi YE, et al. Intensity of 18fluorodeoxyglucose uptake in positron emission tomography distinguishes between indolent and aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2005;23:4643–51.

    Article  PubMed  Google Scholar 

  15. Ngeow JY, Quek RH, Ng DC, Hee SW, Tao M, Lim LC, et al. High SUV uptake on FDG-PET/CT predicts for an aggressive B-cell lymphoma in a prospective study of primary FDG-PET/CT staging in lymphoma. Ann Oncol. 2009;20:1543–7.

    Article  PubMed  CAS  Google Scholar 

  16. Karam M, Ata A, Irish K, Feustel PJ, Mottaghy FM, Stroobants SG, et al. FDG positron emission tomography/computed tomography scan may identify mantle cell lymphoma patients with unusually favorable outcome. Nucl Med Commun. 2009;30:770–8.

    Article  PubMed  Google Scholar 

  17. Gallamini A, Hutchings M, Rigacci L, Specht L, Merli F, Hansen M, et al. Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin’s lymphoma: a report from a joint Italian-Danish study. J Clin Oncol. 2007;25:3746–52.

    Article  PubMed  CAS  Google Scholar 

  18. Haioun C, Itti E, Rahmouni A, Brice P, Rain JD, Belhadj K, et al. [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome. Blood. 2005;106:1376–81.

    Article  PubMed  CAS  Google Scholar 

  19. Liu IJ, Zafar MB, Lai YH, Segall GM, Terris MK. Fluorodeoxyglucose positron emission tomography studies in diagnosis and staging of clinically organ-confined prostate cancer. Urology. 2001;57:108–11.

    Article  PubMed  CAS  Google Scholar 

  20. Sung J, Espiritu JI, Segall GM, Terris MK. Fluorodeoxyglucose positron emission tomography studies in the diagnosis and staging of clinically advanced prostate cancer. BJU Int. 2003;92:24–7.

    Article  PubMed  CAS  Google Scholar 

  21. Schöder H, Herrmann K, Gönen M, Hricak H, Eberhard S, Scardino P, et al. 2-[18F]fluoro-2-deoxyglucose positron emission tomography for the detection of disease in patients with prostate-specific antigen relapse after radical prostatectomy. Clin Cancer Res. 2005;11:4761–9.

    Article  PubMed  Google Scholar 

  22. Richter JA, Rodríguez M, Rioja J, Peñuelas I, Martí-Climent J, Garrastachu P, et al. Dual tracer 11C-choline and FDG-PET in the diagnosis of biochemical prostate cancer relapse after radical treatment. Mol Imaging Biol. 2010;12:210–7.

    Article  PubMed  Google Scholar 

  23. Oyama N, Akino H, Suzuki Y, Kanamaru H, Miwa Y, Tsuka H, et al. Prognostic value of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging for patients with prostate cancer. Mol Imaging Biol. 2002;4:99–104.

    Article  PubMed  Google Scholar 

  24. Fiorentino M, Capizzi E, Loda M. Blood and tissue biomarkers in prostate cancer: state of the art. Urol Clin North Am. 2010;37:131–41.

    Article  PubMed  Google Scholar 

  25. Park JW, Kim JH, Kim SK, Kang KW, Park KW, Choi JI, et al. A prospective evaluation of 18F-FDG and 11C-acetate PET/CT for detection of primary and metastatic hepatocellular carcinoma. J Nucl Med. 2008;49:1912–21.

    Article  PubMed  Google Scholar 

  26. Hatano E, Ikai I, Higashi T, Teramukai S, Torizuka T, Saga T, et al. Preoperative positron emission tomography with fluorine-18-fluorodeoxyglucose is predictive of prognosis in patients with hepatocellular carcinoma after resection. World J Surg. 2006;30:1736–41.

    Article  PubMed  Google Scholar 

  27. Torizuka T, Tamaki N, Inokuma T, Magata Y, Sasayama S, Yonekura Y, et al. In vivo assessment of glucose metabolism in hepatocellular carcinoma with FDG-PET. J Nucl Med. 1995;36:1811–7.

    PubMed  CAS  Google Scholar 

  28. Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman WA, Kooij PP, Oei HY, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med. 1993;20:716–31.

    Article  PubMed  CAS  Google Scholar 

  29. Hoegerle S, Altehoefer C, Ghanem N, Koehler G, Waller CF, Scheruebl H, et al. Whole-body 18F dopa PET for detection of gastrointestinal carcinoid tumors. Radiology. 2001;220:373–80.

    PubMed  CAS  Google Scholar 

  30. Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, et al. [68Ga]DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med. 2007;48:508–18.

    Article  PubMed  CAS  Google Scholar 

  31. Campana D, Ambrosini V, Pezzilli R, Fanti S, Labate AM, Santini D, et al. Standardized uptake values of (68)Ga-DOTANOC PET: a promising prognostic tool in neuroendocrine tumors. J Nucl Med. 2010;51:353–9.

    Article  PubMed  Google Scholar 

  32. Ambrosini V, Campana D, Bodei L, Nanni C, Castellucci P, Allegri V, et al. 68Ga-DOTANOC PET/CT clinical impact in patients with neuroendocrine tumors. J Nucl Med. 2010;51:669–73.

    Article  PubMed  Google Scholar 

  33. Adams S, Baum R, Rink T, Schumm-Dräger PM, Usadel KH, Hör G. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumors. Eur J Nucl Med. 1998;25:79–83.

    Article  PubMed  CAS  Google Scholar 

  34. Wild D, Mäcke HR, Waser B, Reubi JC, Ginj M, Rasch H, et al. [68Ga]DOTANOC: a first compound for PET imaging with high affinity for somatostatin receptor subtypes 2 and 5. Eur J Nucl Med Mol Imaging. 2005;32:724.

    Article  PubMed  Google Scholar 

  35. Binderup T, Knigge U, Loft A, Mortensen J, Pfeifer A, Federspiel B, et al. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET. J Nucl Med. 2010;51:704–12.

    Article  PubMed  Google Scholar 

  36. Binderup T, Knigge U, Loft A, Federspiel B, Kjaer A. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res. 2010;16:978–85.

    Article  PubMed  CAS  Google Scholar 

  37. Garin E, Le Jeune F, Devillers A, Cuggia M, de Lajarte-Thirouard AS, Bouriel C, et al. Predictive value of 18F-FDG PET and somatostatin receptor scintigraphy in patients with metastatic endocrine tumors. J Nucl Med. 2009;50:858–64.

    Article  PubMed  CAS  Google Scholar 

  38. Rubello D, Rampin L, Nanni C, Banti E, Ferdeghini M, Fanti S, et al. The role of 18F-FDG PET/CT in detecting metastatic deposits of recurrent medullary thyroid carcinoma: a prospective study. Eur J Surg Oncol. 2008;34:581–6.

    PubMed  CAS  Google Scholar 

  39. Conry BG, Papathanasiou ND, Prakash V, Kayani I, Caplin M, Mahmood S, et al. Comparison of (68)Ga-DOTATATE and (18)F-fluorodeoxyglucose PET/CT in the detection of recurrent medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2010;37:49–57.

    Article  PubMed  CAS  Google Scholar 

  40. Higashi K, Ueda Y, Seki H, Yuasa K, Oguchi M, Noguchi T, et al. Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med. 1998;39:1016–20.

    PubMed  CAS  Google Scholar 

  41. Goudarzi B, Jacene HA, Wahl RL. Diagnosis and differentiation of bronchioloalveolar carcinoma from adenocarcinoma with bronchioloalveolar components with metabolic and anatomic characteristics using PET/CT. J Nucl Med. 2008;49:1585–92.

    Article  PubMed  Google Scholar 

  42. Padma MV, Said S, Jacobs M, Hwang DR, Dunigan K, Satter M, et al. Prediction of pathology and survival by FDG PET in gliomas. J Neurooncol. 2003;64:227–37.

    Article  PubMed  CAS  Google Scholar 

  43. Kidd EA, Spencer CR, Huettner PC, Siegel BA, Dehdashti F, Rader JS, et al. Cervical cancer histology and tumor differentiation affect 18F-fluorodeoxyglucose uptake. Cancer. 2009;115:3548–54.

    Article  PubMed  Google Scholar 

  44. Kidd EA, Siegel BA, Dehdashti F, Grigsby PW. The standardized uptake value for F-18 fluorodeoxyglucose is a sensitive predictive biomarker for cervical cancer treatment response and survival. Cancer. 2007;110:1738–44.

    Article  PubMed  Google Scholar 

  45. Pan L, Gu P, Huang G, Xue H, Wu S. Prognostic significance of SUV on PET/CT in patients with esophageal cancer: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2009;21:1008–15.

    Article  PubMed  Google Scholar 

  46. Kato H, Nakajima M, Sohda M, Tanaka N, Inose T, Miyazaki T, et al. The clinical application of (18)F-fluorodeoxyglucose positron emission tomography to predict survival in patients with operable esophageal cancer. Cancer. 2009;115:3196–203.

    Article  PubMed  Google Scholar 

  47. Sepesi B, Raymond DP, Polomsky M, Watson TJ, Litle VR, Jones CE, et al. Does the value of PET-CT extend beyond pretreatment staging? An analysis of survival in surgical patients with esophageal cancer. J Gastrointest Surg. 2009;13:2121–7.

    Article  PubMed  Google Scholar 

  48. Scully RE. International histological classification of tumors: histological typing of ovarian tumors. Geneva: World Health Organization; 1999.

    Google Scholar 

  49. Nanni C, Rubello D, Farsad M, De Iaco P, Sansovini M, Erba P, et al. (18)F-FDG PET/CT in the evaluation of recurrent ovarian cancer: a prospective study on forty-one patients. Eur J Surg Oncol. 2005;31:792–7.

    Article  PubMed  CAS  Google Scholar 

  50. Havrilesky LJ, Kulasingam SL, Matchar DB, Myers ER. FDG-PET for management of cervical and ovarian cancer. Gynecol Oncol. 2005;97:183–91.

    Article  PubMed  Google Scholar 

  51. Kumar R, Alavi A. PET imaging in gynecologic malignancies. Radiol Clin North Am. 2004;42:1155–67.

    Article  PubMed  Google Scholar 

  52. Fenchel S, Grab D, Nuessle K, Kotzerke J, Rieber A, Kreienberg R, et al. Asymptomatic adnexal masses: correlation of FDG PET and histopathologic findings. Radiology. 2002;223:780–8.

    Article  PubMed  Google Scholar 

  53. Rieber A, Nüssle K, Stöhr I, Grab D, Fenchel S, Kreienberg R, et al. Preoperative diagnosis of ovarian tumors with MR imaging: comparison with transvaginal sonography, positron emission tomography, and histologic findings. AJR Am J Roentgenol. 2001;177:123–9.

    PubMed  CAS  Google Scholar 

  54. Woodward PJ, Hosseinzadeh K, Saenger JS. From the archives of the AFIP: radiologic staging of ovarian carcinoma with pathologic correlation. Radiographics. 2004;24:225–46.

    Article  PubMed  Google Scholar 

  55. Huang YT, Lee JC, Kumar AS. Variable F-18 fluorodeoxyglucose avidity of metastatic recurrent adult granulosa cell tumor. Clin Nucl Med. 2009;34:710–2.

    Article  PubMed  CAS  Google Scholar 

  56. Picchio M, Sironi S, Messa C, Mangili G, Landoni C, Gianolli L. Advanced ovarian carcinoma: usefulness of [(18)F]FDG-PET in combination with CT for lesion detection after primary treatment. Q J Nucl Med. 2003;47:77–84.

    PubMed  CAS  Google Scholar 

  57. Risum S, Høgdall C, Loft A, Berthelsen AK, Høgdall E, Nedergaard L, et al. The diagnostic value of PET/CT for primary ovarian cancer: a prospective study. Gynecol Oncol. 2007;105:145–9.

    Article  PubMed  Google Scholar 

  58. Yamamoto Y, Oguri H, Yamada R, Maeda N, Kohsaki S, Fukaya T. Preoperative evaluation of pelvic masses with combined 18F-fluorodeoxyglucose positron emission tomography and computed tomography. Int J Gynecol Obstet. 2008;102:124–7.

    Article  Google Scholar 

  59. Jung DC, Choi HJ, Ju W, Kim SC, Choi KG. Discordant MRI/FDG-PET imaging for the diagnosis of borderline ovarian tumors. Int J Gynecol Cancer. 2008;18:637–41.

    Article  PubMed  CAS  Google Scholar 

  60. Schröder W, Zimny M, Rudlowski C, Bull U, Rath W. The role of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in diagnosis of ovarian cancer. Int J Gynecol Cancer. 1999;9:117–22.

    Article  PubMed  Google Scholar 

  61. Kurokawa T, Yoshida Y, Kawahara K, Tsuchida T, Okazawa H, Fujibayashi Y, et al. Expression of GLUT-1 glucose transfer, cellular proliferation activity and grade of tumor correlate with [F-18]-fluorodeoxyglucose uptake by positron emission tomography in epithelial tumors of the ovary. Int J Cancer. 2004;109:926–32.

    Article  PubMed  CAS  Google Scholar 

  62. Kalir T, Wang BY, Goldfischer M, Haber RS, Reder I, Demopoulos R, et al. Immunohistochemical staining of GLUT1 in benign, borderline, and malignant ovarian epithelia. Cancer. 2002;15:1078–82.

    Article  Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands

    Thomas C. Kwee

  2. Radiation Medicine Center (Bhabha Atomic Research Center), Tata Memorial Center Annexe, Bombay, India

    Sandip Basu

  3. Division of Nuclear Medicine, Hospital of the University of Pennsylvania, Spruce St., 110 Donner Bldg, Philadelphia, PA, 3400 19104, USA

    Sandip Basu, Babak Saboury, Drew A. Torigian & Abass Alavi

  4. Department of Nuclear Medicine, Sant’ Orsola-Malpighi University Hospital, Bologna, Italy

    Valentina Ambrosini

Authors
  1. Thomas C. Kwee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandip Basu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Babak Saboury
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Valentina Ambrosini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Drew A. Torigian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Abass Alavi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abass Alavi.

Additional information

Thomas C. Kwee and Sandip Basu contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kwee, T.C., Basu, S., Saboury, B. et al. A new dimension of FDG-PET interpretation: assessment of tumor biology. Eur J Nucl Med Mol Imaging 38, 1158–1170 (2011). https://doi.org/10.1007/s00259-010-1713-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-010-1713-9

Keywords

Search

Navigation