title: 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.
abstract: BACKGROUND
  The detection of occult bone metastases is a key factor in determining the management of patients with renal cell carcinoma (RCC), especially when curative surgery is considered. This prospective study assessed the sensitivity of (18)F-labelled sodium fluoride in conjunction with positron emission tomography/computed tomography ((18)F-NaF PET/CT) for detecting RCC bone metastases, compared with conventional imaging by bone scintigraphy or CT.
  
  
  METHODS
  An adaptive two-stage trial design was utilized, which was stopped after the first stage due to statistical efficacy. Ten patients with stage IV RCC and bone metastases were imaged with (18)F-NaF PET/CT and (99m)Tc-labelled methylene diphosphonate ((99m)Tc-MDP) bone scintigraphy including pelvic single photon emission computed tomography (SPECT). Images were reported independently by experienced radiologists and nuclear medicine physicians using a 5-point scoring system.
  
  
  RESULTS
  Seventy-seven lesions were diagnosed as malignant: 100% were identified by (18)F-NaF PET/CT, 46% by CT and 29% by bone scintigraphy/SPECT. Standard-of-care imaging with CT and bone scintigraphy identified 65% of the metastases reported by (18)F-NaF PET/CT. On an individual patient basis, (18)F-NaF PET/CT detected more RCC metastases than (99m)Tc-MDP bone scintigraphy/SPECT or CT alone (P = 0.007). The metabolic volumes, mean and maximum standardized uptake values (SUV mean and SUV max) of the malignant lesions were significantly greater than those of the benign lesions (P < 0.001).
  
  
  CONCLUSIONS
  (18)F-NaF PET/CT is significantly more sensitive at detecting RCC skeletal metastases than conventional bone scintigraphy or CT. The detection of occult bone metastases could greatly alter patient management, particularly in the context when standard-of-care imaging is negative for skeletal metastases.
authors.affiliation: Department of Radiology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge.
authors.forename: E L
authors.initials: EL
authors.lastname: Gerety
authors.affiliation: Department of Radiology, University of Cambridge, Cambridge.
authors.forename: E M
authors.initials: EM
authors.lastname: Lawrence
authors.affiliation: MRC Biostatistics Unit Hub for Trials Methodology, Cambridge.
authors.forename: J
authors.initials: J
authors.lastname: Wason
authors.affiliation: Department of Radiology, University of Cambridge, Cambridge.
authors.forename: H
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Radiology, University of Cambridge, Cambridge.
authors.forename: S
authors.initials: S
authors.lastname: Hilborne
authors.affiliation: Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge.
authors.forename: J
authors.initials: J
authors.lastname: Buscombe
authors.affiliation: Department of Radiology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge.
authors.forename: H K
authors.initials: HK
authors.lastname: Cheow
authors.affiliation: Department of Radiology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge.
authors.forename: A S
authors.initials: AS
authors.lastname: Shaw
authors.affiliation: East Anglian Regional Radiation Protection Service, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge.
authors.forename: N
authors.initials: N
authors.lastname: Bird
authors.affiliation: Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge.
authors.forename: K
authors.initials: K
authors.lastname: Fife
authors.affiliation: Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge.
authors.forename: S
authors.initials: S
authors.lastname: Heard
authors.affiliation: Department of Radiology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge Department of Radiology, University of Cambridge, Cambridge.
authors.forename: D J
authors.initials: DJ
authors.lastname: Lomas
authors.affiliation: Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge.
authors.forename: A
authors.initials: A
authors.lastname: Matakidou
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge.
authors.forename: D
authors.initials: D
authors.lastname: Soloviev
authors.affiliation: Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge Department of Oncology, University of Cambridge, Cambridge, UK.
authors.forename: T
authors.initials: T
authors.lastname: Eisen
authors.affiliation: Department of Radiology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Health Partners, Cambridge Department of Radiology, University of Cambridge, Cambridge fag1000@cam.ac.uk.
authors.forename: F A
authors.initials: FA
authors.lastname: Gallagher
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*; D002291:Carcinoma, Papillary / Q000000981:diagnostic imaging / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000556:secondary; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005500:Follow-Up Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D011877:Radionuclide Imaging; D012107:Research Design; D012680:Sensitivity and Specificity; D013669:Technetium Tc 99m Medronate / Q000493:pharmacokinetics*; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D019788:Fluorodeoxyglucose F18; D013669:Technetium Tc 99m Medronate
keywords: 18F-NaF PET/CT; 99mTc-MDP bone scintigraphy; bone metastases; computed tomography; renal cell carcinoma