Prospective comparison of combined 18F-FDG and 18F-NaF PET/CT vs. 18F-FDG PET/CT imaging for detection of malignancy

  • Frank I. Lin
  • Jyotsna E. Rao
  • Erik S. Mittra
  • Kavitha Nallapareddy
  • Alka Chengapa
  • David W. Dick
  • Sanjiv Sam Gambhir
  • Andrei IagaruEmail author
Original Article



Typically, 18F-FDG PET/CT and 18F-NaF PET/CT scans are done as two separate studies on different days to allow sufficient time for the radiopharmaceutical from the first study to decay. This is inconvenient for the patients and exposes them to two doses of radiation from the CT component of the examinations. In the current study, we compared the clinical usefulness of a combined 18F-FDG/18F-NaF PET/CT scan with that of a separate 18F-FDG-only PET/CT scan.


There were 62 patients enrolled in this prospective trial. All had both an 18F-FDG-alone PET/CT scan and a combined 18F-FDG/18F-NaF PET/CT scan. Of the 62 patients, 53 (85%) received simultaneous tracer injections, while 9 (15%) received 18F-NaF subsequent to the initial 18F-FDG dose (average delay 2.2 h). Images were independently reviewed for PET findings by two Board-Certified nuclear medicine physicians, with discrepancies resolved by a third reader. Interpreters were instructed to only report findings that were concerning for malignancy. Reading the 18F-FDG-only scan first for half of the patients controlled for order bias.


In 15 of the 62 patients (24%) neither the 18F-FDG-only PET/CT scan nor the combined 18F-FDG/18F-NaF PET/CT scan identified malignancy. In the remaining 47 patients who had PET findings of malignancy, a greater number of lesions were detected in 16 of 47 patients (34%) using the combined 18F-FDG/18F-NaF PET/CT scan compared to the 18F-FDG-only PET/CT scan. In 2 of these 47 patients (4%), the 18F-FDG-only scan demonstrated soft tissue lesions that were not prospectively identified on the combined study. In 29 of these 47 patients (62%), the combined scan detected an equal number of lesions compared to the 18F-FDG-only scan. Overall, 60 of all the 62 patients (97%) showed an equal or greater number of lesions on the combined scan than on the 18F-FDG-only scan.


The current study demonstrated that 18F-FDG and 18F-NaF can be combined in a single PET/CT scan by administering the two radiopharmaceuticals simultaneously or in sequence on the same day. In addition to patient convenience and reduced radiation exposure from the CT component, the combined 18F-FDG/18F-NaF PET/CT scan appeared to increase the sensitivity for detection of osseous lesions compared to the 18F-FDG-only PET/CT scan in the studied population.


PET/CT combined scan PET/CT bone imaging 18F-NaF PET/CT Osseous lesion detection 



This research was supported in part by NCI ICMIC CA114747 (S.S.G.) and clinical studies were supported in part by the Doris Duke Foundation and Canary Foundation (S.S.G.). We would also like to thank Mr. Atul Gada (senior technologist) whose help and support was immense.

Conflicts of interest



  1. 1.
    Huyge V, Garcia C, Vanderstappen A, Alexiou J, Gil T, Flamen P. Progressive osteoblastic bone metastases in breast cancer negative on FDG-PET. Clin Nucl Med. 2009;34(7):417–20.PubMedCrossRefGoogle Scholar
  2. 2.
    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;32(11):1253–8.PubMedCrossRefGoogle Scholar
  3. 3.
    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.PubMedGoogle Scholar
  4. 4.
    Chua S, Gnanasegaran G, Cook G. Miscellaneous cancers (lung, thyroid, renal cancer, myeloma, and neuroendocrine tumors): role of SPECT and PET in imaging bone metastases. Semin Nucl Med. 2009;39(6):416–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Schirrmeister H, Glatting G, Hetzel J, Nüssle K, Arslandemir C, Buck AK, et al. Prospective evaluation of the clinical value of planar bone scans, SPECT, and (18)F-labeled NaF PET in newly diagnosed lung cancer. J Nucl Med. 2001;42(12):1800–4.PubMedGoogle Scholar
  6. 6.
    Savelli G, Maffioli L, Maccauro M, De Deckere E, Bombardieri E. Bone scintigraphy and the added value of SPECT (single photon emission tomography) in detecting skeletal lesions. Q J Nucl Med. 2001;45(1):27–37.PubMedGoogle Scholar
  7. 7.
    Bybel B, Brunken R, DiFilippo F, Neumann D, Wu G, Cerqueira M. SPECT/CT imaging: clinical utility of an emerging technology. Radiographics. 2008;28(4):1097–113.PubMedCrossRefGoogle Scholar
  8. 8.
    Eftekhari F. Imaging assessment of osteosarcoma in childhood and adolescence: diagnosis, staging, and evaluating response to chemotherapy. Cancer Treat Res. 2009;152:33–62.PubMedCrossRefGoogle Scholar
  9. 9.
    James SL, Panicek DM, Davies AM. Bone marrow oedema associated with benign and malignant bone tumours. Eur J Radiol. 2008;67(1):11–21.PubMedCrossRefGoogle Scholar
  10. 10.
    Schmidt G, Reiser M, Baur-Melnyk A. Whole-body MRI for the staging and follow-up of patients with metastasis. Eur J Radiol. 2009;70(3):393–400.PubMedCrossRefGoogle Scholar
  11. 11.
    Bäuerle T, Semmler W. Imaging response to systemic therapy for bone metastases. Eur Radiol. 2009;19(10):2495–507.PubMedCrossRefGoogle Scholar
  12. 12.
    Blau M, Nagler W, Bender MA. Fluorine-18: a new isotope for bone scanning. J Nucl Med. 1962;3:332–4.PubMedGoogle Scholar
  13. 13.
    Dasgeb B, Mulligan M, Kim C. The current status of bone scintigraphy in malignant diseases. Semin Musculoskelet Radiol. 2007;11(4):301–11.PubMedCrossRefGoogle Scholar
  14. 14.
    National Cancer Institute. New drug for use in bone scans approved; provides an alternative to radioactive tracer that is currently in short supply. Updated 1 Feb 2011. Accessed 27 Oct 2011.
  15. 15.
    National Oncologic PET Registry. NOPR Update: NOPR announcement regarding coverage change implementation. Updated 1 Feb 2011. Accessed 27 Oct 2011.
  16. 16.
    Fogelman I, Cook G, Israel O, Van der Wall H. Positron emission tomography and bone metastases. Breast Dis. 2005;35(2):135–42.Google Scholar
  17. 17.
    Hetzel M, Arslandemir C, König HH, Buck AK, Nüssle K, Glatting G, et al. F-18 NaF PET for detection of bone metastases in lung cancer: accuracy, cost-effectiveness, and impact on patient management. J Bone Miner Res. 2003;18(12):2206–14.PubMedCrossRefGoogle Scholar
  18. 18.
    Petrén-Mallmin M, Andréasson I, Ljunggren O, Ahlström H, Bergh J, Antoni G, et al. Skeletal metastases from breast cancer: uptake of 18F-fluoride measured with positron emission tomography in correlation with CT. Skeletal Radiol. 1998;27(2):72–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Schirrmeister H, Guhlmann A, Elsner K, Kotzerke J, Glatting G, Rentschler M, et al. Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET. J Nucl Med. 1999;40(10):1623–9.PubMedGoogle Scholar
  20. 20.
    Iagaru A, Mittra E, Yaghoubi S, Dick DW, Quon A, Goris ML, et al. Novel strategy for a cocktail 18F-fluoride and 18F-FDG PET/CT scan for evaluation of malignancy: results of the pilot-phase study. J Nucl Med. 2009;50(4):501–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Centers for Medicare and Medicaid Services. National Coverage Determination (NCD) for Positron Emission Tomogtaphy (FDG) for Oncologic Conditions (220.6.17). 2010; Accessed Sep 01, 2011.
  22. 22.
    Christensen JA, Nathan MA, Mullan BP, Hartman TE, Swensen SJ, Lowe VJ. Characterization of the solitary pulmonary nodule: 18F-FDG PET versus nodule-enhancement CT. AJR Am J Roentgenol. 2006;187(5):1361–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007;25(5):571–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Gallowitsch H-J, Kresnik E, Gasser J, Kumnig G, Igerc I, Mikosch P, et al. F-18 fluorodeoxyglucose positron-emission tomography in the diagnosis of tumor recurrence and metastases in the follow-up of patients with breast carcinoma: a comparison to conventional imaging. Invest Radiol. 2003;38(5):250–6.PubMedGoogle Scholar
  25. 25.
    Moon DH, Maddahi J, Silverman DH, Glaspy JA, Phelps ME, Hoh CK. Accuracy of whole-body fluorine-18-FDG PET for the detection of recurrent or metastatic breast carcinoma. J Nucl Med. 1998;39(3):431–5.PubMedGoogle Scholar
  26. 26.
    Grant F, Fahey F, Packard A, Davis R, Alavi A, Treves T. Skeletal PET with 18F-fluoride: applying new technology to an old tracer. J Nucl Med. 2008;49(1):68–78.PubMedCrossRefGoogle Scholar
  27. 27.
    Hoegerle S, Juengling F, Otte A, Altehoefer C, Moser EA, Nitzsche EU. Combined FDG and [F-18]fluoride whole-body PET: a feasible two-in-one approach to cancer imaging? Radiology. 1998;209(1):253–8.PubMedGoogle Scholar
  28. 28.
    Messiou C, Cook G, deSouza NM. Imaging metastatic bone disease from carcinoma of the prostate. Br J Cancer. 2009;101(8):1225–32.PubMedCrossRefGoogle Scholar
  29. 29.
    Takenaka D, Ohno Y, Matsumoto K, Aoyama N, Onishi Y, Koyama H, et al. Detection of bone metastases in non-small cell lung cancer patients: comparison of whole-body diffusion-weighted imaging (DWI), whole-body MR imaging without and with DWI, whole-body FDG-PET/CT, and bone scintigraphy. J Magn Reson Imaging. 2009;30(2):298–308.PubMedCrossRefGoogle Scholar
  30. 30.
    Kwee T, Takahara T, Ochiai R, Koh DM, Ohno Y, Nakanishi K, et al. Complementary roles of whole-body diffusion-weighted MRI and 18F-FDG PET: the state of the art and potential applications. J Nucl Med. 2010;51(10):1549–58.PubMedCrossRefGoogle Scholar
  31. 31.
    Nakanishi K, Kobayashi M, Nakaguchi K, Kyakuno M, Hashimoto N, Onishi H, et al. Whole-body MRI for detecting metastatic bone tumor: diagnostic value of diffusion-weighted images. Magn Reson Med Sci. 2007;6(3):147–55.PubMedCrossRefGoogle Scholar
  32. 32.
    Taira A, Herfkens R, Gambhir S, Quon A. Detection of bone metastases: assessment of integrated FDG PET/CT imaging. Radiology. 2007;243(1):204–11.PubMedCrossRefGoogle Scholar
  33. 33.
    Blomqvist C, Elomaa I, Virkkunen P, Porkka L, Karonen SL, Risteli L, et al. The response evaluation of bone metastases in mammary carcinoma. The value of radiology, scintigraphy, and biochemical markers of bone metabolism. Cancer. 1987;60(12):2907–12.PubMedCrossRefGoogle Scholar
  34. 34.
    Hird A, Chow E, Zhang L, Wong R, Wu J, Sinclair E, et al. Determining the incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: results from three Canadian cancer centers. Int J Radiat Oncol Biol Phys. 2009;75(1):193–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Segall G, Delbeke D, Stabin M, Even-Sapir E, Fair J, Sajdak R, et al. SNM practice guideline for sodium 18F-fluoride PET/CT bone scans 1.0. J Nucl Med. 2010;51(11):1813–20.PubMedCrossRefGoogle Scholar
  36. 36.
    Krüger S, Buck A, Mottaghy F, Hasenkamp E, Pauls S, Schumann C, et al. Detection of bone metastases in patients with lung cancer: 99mTc-MDP planar bone scintigraphy, 18F-fluoride PET or 18F-FDG PET/CT. Eur J Nucl Med Mol Imaging. 2009;36(11):1807–12.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Frank I. Lin
    • 1
  • Jyotsna E. Rao
    • 2
  • Erik S. Mittra
    • 1
  • Kavitha Nallapareddy
    • 2
  • Alka Chengapa
    • 2
  • David W. Dick
    • 3
  • Sanjiv Sam Gambhir
    • 4
  • Andrei Iagaru
    • 1
    Email author
  1. 1.Division of Nuclear MedicineStanford University Medical CenterStanfordUSA
  2. 2.Apollo Gleneagles PET-CT CentreHyderabadIndia
  3. 3.Cyclotron PhysicsMolecular Imaging Program at Stanford (MIPS)StanfordUSA
  4. 4.Departments of Radiology, Bioengineering, Materials Science and EngineeringMolecular Imaging Program at Stanford (MIPS)StanfordUSA

Personalised recommendations