The role of combined 18-Fluoride Positron Emission Tomography and Computed Tomography in the detection of bone metastases in patients with renal cell carcinoma.
Positron emission tomography is used to detect the localization of positron-emitting radiotracers such as 18-Fluorine (18F). Standard PET for tumour localisation images the distribution of 18-Fluoride-labeled fluoro-deoxyglucose (18F-FDG), a glucose analogue which has high uptake by metabolically active cells including tumour cells. However, fluoride itself is taken up by metabolically active bone such as in bone metastases and has been investigated for its role in the detection of prostate, breast and thyroid metastases. Computed tomography (CT) images acquired at the same time as the PET images (18F-NaF PET/CT) enable anatomic localization of the 18F uptake.
Our study investigated the role of 18F-NaF PET/CT in detecting bone metastases in patients with Renal Cell Cancer (RCC). It is particularly important to detect bone metastases in patients with RCC as their presence or absence changes management: patients with a single bone metastasis may be offered metastatectomy; patients with multiple bone metastases may be offered systemic therapies or palliative management. One third of those patients treated with curative intent later develop metastatic disease which may have been present as undetectable, occult metastases at the time of surgery. It is therefore important to develop more sensitive tests for the detection of bone metastases at an early stage. It has also become more important to have sensitive imaging tests to assess the efficacy of novel therapies for RCC that are being developed.
Our study, in collaboration with the Department of Oncology, Cancer Research UK Cambridge Institute and the MRC Biostatistics Unit Hub for Trials Methodology, aimed to determine the sensitivity of 18F-NaF PET/CT compared to standard of care bone scintigraphy and CT alone. The study was novel in that it used an adaptive 2-stage trial design. In stage one, 10 patients were enrolled and imaged with 18F-Na PET/CT and bone scintigraphy with pelvic SPECT. The results were analysed after this first stage and found to be statistically significant, resulting in the end of the trial.
We found that 18F-NaF PET/CT was significantly more sensitive than CT alone, bone scintigraphy or CT and bone scintigraphy combined. 18F-NaF PET/CT detected 3 times as many bone metastases as bone scintigraphy and 2 times as many bone metastases as CT alone. Future projects are being planned to investigate the usefulness of 18F-NaF PET/CT in the clinical setting and whether it should be routinely performed in the staging of patients with renal cancer.
Gerety EL, Lawrence EM, Wason J, Yan H, Hilborne S, Buscombe J, Cheow HK, Shaw AS, Bird N, Fife K, Heard S, Lomas DJ, Matakidou A, Soloviev D, Eisen T, Gallagher FA. Prospective study evaluating the 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. Annals of Oncology 2015; 26(10):2113-8.
Comment in Nature Reviews, clinical oncology 2015; 12:5.
Hutchinson L. Improving detection of bone metastases.