Abstract
18F-NaF PET/CT plays an essential role in initial staging, detection of suspected first skeletal metastasis, the suspected progression of bony metastases, or treatment monitoring in many types of cancer, such as prostate, breast, and lung cancer. The morphology and extent of osteoblastic bone metastases, especially when widespread throughout the skeleton, pose a challenge for conventional anatomic imaging to determine tumor load and to evaluate response to therapy. Conventional bone scintigraphy (BS) has been consistently proven to be an inaccurate and insensitive imaging tool to assess response to treatment in many metastatic cancers. 18F-Fluoride PET/CT can determine and assess the whole bone tumor burden quantitatively. Furthermore, 18F-Fluoride (a bone-seeking radiotracer for diagnosis) has uptake properties similar to a therapeutic radiotracer such as 223Ra (the bone-seeking radiotracer for therapy) has the potential to precisely assess the possibility and efficacy of a treatment. In this chapter, we review the use of 18F-NaF PET/CT in prostate, breast, lung, thyroid, and renal cell cancer and discuss 18F-NaF PET/CT’s capability to monitor therapy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Lin C, Bradshaw T, Perk T, Harmon S, Eickhoff J, Jallow N, et al. Repeatability of quantitative 18F-NaF PET: a multicenter study. J Nucl Med. 2016;57:1872–9.
Segall G, Delbeke D, Stabin MG, et al. SNM practice guideline for sodium 18F-fluoride PET/CT bone scans 1.0. J Nucl Med. 2010;51:1813–20.
Bortot DC, Amorim BJ, Oki GC, Gapski SB, Santos AO, Lima MC, et al. 18F-fluoride PET/CT is highly effective for excluding bone metastases even in patients with equivocal bone scintigraphy. Eur J Nucl Med Mol Imaging. 2012;39:1730–6.
Shen C, Qiu Z, Han T, Luo Q. Performance of 18F-fluoride PET or PET/CT for the detection of bone metastases. A meta-analysis. Clin Nucl Med. 2015;40:103–10.
Minamimoto R, Loening A, Jamali M, Barkhodari A, Mosci C, Jackson T, et al. Prospective comparison of 99mTc-MDP Scintigraphy, combined 18F-NaF and 18F-FDG PET/CT, and whole-body MRI in patients with breast and prostate cancer. J Nucl Med. 2015;56:1862–8.
Broos W, van der Zant FM, Wondergem M, Knol RJJ. Accuracy of 18F-NaF PET/CT in bone metastasis detection and its effect on patient management in patients with breast carcinoma. Nucl Med Commun. 2018;39:325–33.
Even-Sapir E, Metser U, Mishani E, Lievshitz G, Lerman H, Leibovitch I. The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT. J Nucl Med. 2006;47:287–97.
Kruger S, Buck AK, Mottaghy FM, 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;36:1807–12.
Rao L, Zong Z, Chen Z, Wang X, Shi X, Yi C, et al. 18F-labeled NaF PET-CT in detection of bone metastases in patients with preoperative lung Cancer. Medicine. 2016;95:e3490.
Sharma P, Karunanithi S, Chakraborty PS, Kumar R, Seth A, Julka PK, Bal C, Kumar R. 18F-fluoride PET/CT for detection of bone metastasis in patients with renal cell carcinoma: a pilot study. Nucl Med Commun. 2014;35:1247–53.
Gerety EL, Lawrence EM, Wason J, Yan H, Hilborne S, Buscombe J, et al. Prospective study evaluating the relative sensitivity of 18F-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and 99mTc-MDP bone scintigraphy, using an adaptive trial design. Ann Oncol. 2015;26:2113–8.
Hillner BE, Siegel BA, Hanna L, Duan F, Quinn B, Shields AF. 18F-fluoride PET used for treatment monitoring of systemic cancer therapy: results from the National Oncologic PET registry. J Nucl Med. 2015;56:222–8.
Oyen W, Sundram F, Haug AR, Kairemo K, Maenpaa H, Mottaghy F, et al. Radium-223 dichloride (Ra-223) for the treatment of metastatic castration-resistant prostate cancer: optimizing clinical practice in nuclear medicine centers. J Oncol Pathol. 2015;3:1–25.
Kairemo K, Milton DR, Etchebehere E, et al. Final outcome of 223Ra-therapy and the role of 18F-fluoride-PET in response evaluation in metastatic castration-resistant prostate cancer–a single institution experience. Curr Radiopharm. 2018;11:152–7.
Etchebehere EC, Araujo JC, Fox PS, Swanston NM, Macapinlac HA, Rohren EM. Prognostic factors in patients treated with 223Ra: the role of skeletal tumor burden on baseline 18Ffluoride PET/CT in predicting overall survival. J Nucl Med. 2015;56:1177–84.
von Eyben FE, Kairemo K, Kiljunen T, Joensuu T. Planning of external beam radiotherapy for prostate cancer guided by PET/CT. Curr Radiopharm. 2015;8:19–31.
Scher HI, Sawyers CL. Biology of progressive, castration resistant prostate cancer: directed therapies targeting the androgen receptor signaling axis. J Clin Oncol. 2005;23:8253–61.
Kairemo K, Joensuu T. Radium-223-dichloride in castration resistant metastatic prostate cancer-preliminary results of the response evaluation using F-18-fluoride PET/CT. Diagnostics (Basel). 2015;5:413–27.
Etchebehere E, Brito AE, Rezaee A, et al. Therapy assessment of bone metastatic disease in the era of 223radium. Eur J Nucl Med Mol Imaging. 2017;44(Suppl 1):84–96.
Apolo AB, Lindenberg L, Shih JH, Mena E, Kim JW, Park JC, et al. Prospective study evaluating Na18F PET/CT in predicting clinical outcomes and survival in advanced prostate cancer. J Nucl Med. 2016;57:886–92.
Rohren EM, Etchebehere EC, Araujo JC, Hobbs BP, Swanston NM, Everding M, et al. Determination of skeletal tumor burden on 18F-fluoride PET/CT. J Nucl Med. 2015;56:1507–12.
Lindgren B, Sadik M, Kaboteh R, Hasani N, Enqvist O, Svärm L, Kahl F, Simonsen J, Poulsen M, Ohlsson M, Høilund-Carlsen P, Edenbrandt L, Trägårdh E. 3D skeletal uptake of 18F sodium fluoride in PET/CT images is associated with overall survival in patients with prostate cancer. EJNMMI Res. 2017;7:15.
Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fossa SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.
Letellier A, Johnson AC, Kit NH, Savigny J, Batalla A, Parienti J, Aide N. Uptake of Radium-223 dichloride and early [18F] NaF PET response are driven by baseline [18F]NaF parameters: a pilot study in castration-resistant prostate cancer patients. Mol Imaging Biol. 2018;20:482–91.
Murray I, Chittenden SJ, Denis-Bacelar AM, Hindorf C, Parker C, Chua S, Flux GD. The potential of 223Ra and 18F-fluoride imaging to predict bone lesion response to treatment with 223Ra-dichloride in castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2017;44:1832–44.
Etchebehere EC, Araujo JC, Milton DR, Erwin WD, Wendt RE 3rd, Swanston NM, et al. Skeletal tumor burden on baseline 18F-fluoride PET/CT predicts bone marrow failure after 223Ra therapy. Clin Nucl Med. 2016;41:268–73.
Taube T, Elomaa I, Blomqvist C, Beneton MN, Kanis JA. Histomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer. Bone. 1994;15:161–6.
Brito A, Santos A, Sasse AD, Cabello C, Oliveira P, Mosci C, Souza T, Amorim B, Lima M, Ramos CD, Etchebehere E. 18F-Fluoride PET/CT tumor burden quantification predicts survival in breast cancer. Oncotarget. 2017;8:36001–11.
Azad G, Siddique MM, Taylor B, et al. Does measurement of 18F-fluoride metabolic flux improve response assessment of breast cancer bone metastases compared with standardised uptake values in 18F-fluoride PET/CT? J Nucl Med. 2018. pii: jnumed.118.208710. https://doi.org/10.2967/jnumed.118.208710.
Peterson LM, O’Sullivan J, Wu QV, et al. Prospective study of serial 18F-FDG PET and 18F-fluoride (18F-NaF) PET to predict time to skeletal related events, time-to-progression, and survival in patients with bone-dominant metastatic breast cancer. J Nucl Med. 2018. pii: jnumed.118.211102. https://doi.org/10.2967/jnumed.118.211102.
Rao L, Zong Z, Chen Z, et al. 18F-labeled NaF PET-CT in detection of bone metastases in patients with preoperative lung Cancer. Medicine (Baltimore). 2016;95:e3490.
Lee H, Lee WW, Park SY, Kim SE. F-18 sodium fluoride positron emission tomography/computed tomography for detection of thyroid Cancer bone metastasis compared with bone scintigraphy. Korean J Radiol. 2016;17:281–8. https://doi.org/10.3348/kjr.2016.17.2.281.
Ota N, Kato K, Iwano S, et al. Comparison of 18F-fluoride PET/CT, 18F-FDG PET/CT and bone scintigraphy (planar and SPECT) in detection of bone metastases of differentiated thyroid cancer: a pilot study. Br J Radiol. 2014;87:20130444.
Schirrmeister H, Buck A, Guhlmann A, Reske SN. Anatomical distribution and sclerotic activity of bone metastases from thyroid cancer assessed with F-18 sodium fluoride positron emission tomography. Thyroid. 2001;11:677–83.
Gerety EL, Lawrence EM, Wason J, et al. Prospective study evaluating the relative sensitivity of 18F-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and 99mTc-MDP bone scintigraphy, using an adaptive trial design. Ann Oncol. 2015;26:2113–8.
Sharma P, Karunanithi S, Chakraborty PS, et al. 18F-fluoride PET/CT for detection of bone metastasis in patients with renal cell carcinoma: a pilot study. Nucl Med Commun. 2014;35:1247–53.
Rossleigh MA, Lovegrove FT, Reynolds PM, Byrne MJ. Serial bone scans in the assessment of response to therapy in advanced breast carcinoma. Clin Nucl Med. 1982;7:397–402.
Castello A, Macapinlac HA, Lopci E, Santos EB. Prostate-specific antigen flare induced by 223RaCl2 in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2018. [Epub ahead of print]. https://doi.org/10.1007/s00259-018-4051-y
Balasubramanian Harisankar CN, Preethi R, John J. Metabolic flare phenomenon on 18 fluoride-fluorodeoxy glucose positron emission tomography-computed tomography scans in a patient with bilateral breast cancer treated with second-line chemotherapy and bevacizumab. Indian J Nucl Med. 2015;30:145–7.
Wade AA, Scott JA, Kuter I, Fischman AJ. Flare response in 18F-fluoride ion PET bone scanning. AJR Am J Roentgenol. 2006;186:1783–6.
Cook G Jr, Parker C, Chua S, et al. 18F-fluoride PET: changes in uptake as a method to assess response in bone metastases from castrate-resistant prostate cancer patients treated with 223Ra-chloride (Alpharadin). EJNMMI Res. 2011;1:4.
Etchebehere E, Brito AE, Kairemo K, et al. Interim 18F-fluoride PET/CT is not able to predict outcome after radium-223 therapy. Radiol Bras. 2019;52(1):33–40.
Yu EY, Duan F, Muzi M, et al. Castration-resistant prostate cancer bone metastasis response measured by 18F-fluoride PET after treatment with dasatinib and correlation with progression-free survival: results from American College of Radiology Imaging Network 6687. J Nucl Med. 2015;56:354–60.
Harmon SA, Perk T, Lin C, et al. Quantitative assessment of early [18F] sodium fluoride positron emission tomography/computed tomography response to treatment in men with metastatic prostate cancer to bone. J Clin Oncol. 2017;35:2829–37.
Harmon SA, Bergvall E, Mena E, et al. A prospective comparison of 18F-Sodium Fluoride PET/CT and PSMA-targeted 18F-DCFBC PET/CT in metastatic prostate cancer. J Nucl Med. 2018. pii: jnumed.117.207373. [Epub ahead of print]. https://doi.org/10.2967/jnumed.117.207373
Sachpekidis C, Hillengass J, Goldschmidt H, Wagner B, Haberkorn U, Kopka K, Dimitrakopoulou-Strauss A. Treatment response evaluation with 18F-FDG PET/CT and 18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation. Eur J Nucl Med Mol Imaging. 2017;44:50–62.
Kairemo K, Rohren EM, Anderson PM, et al. Development of sodium fluoride PET response criteria for solid tumours (NAFCIST) in a clinical trial of radium-223 in osteosarcoma: from RECIST to PERCIST to NAFCIST. ESMO Open. 2019;0:e000439. https://doi.org/10.1136/esmoopen-2018-000439.
Subbiah V, Anderson PM, Kairemo K, et al. Alpha particle Radium 223 dichloride in high-risk osteosarcoma: a phase I dose escalation trial. Clin Cancer Res. 2019. pii: clincanres.3964.2018. https://doi.org/10.1158/1078-0432.CCR-18-3964.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Kairemo, K., Macapinlac, H.A. (2021). Treatment Response Evaluation of Bone Metastases Using 18F-NaF. In: Fanti, S., Gnanasegaran, G., Carrió, I. (eds) Atlas of Clinical PET-CT in Treatment Response Evaluation in Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-68858-5_9
Download citation
DOI: https://doi.org/10.1007/978-3-030-68858-5_9
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-68857-8
Online ISBN: 978-3-030-68858-5
eBook Packages: MedicineMedicine (R0)