Editorial: Bone Metastases in Prostate Cancer: Which Scan?

It has become increasingly recognised that planar WBS is no longer the most accurate method of assessing the skeleton for metastases and that novel imaging methods, including PET/CT, single-photon emission CT (SPECT)/CT and whole-body MRI offer advantages [2].

What is surprising in the presented results is that NaF PET/CT shows poor specificity (54%), a result that is discordant with previous literature [3, 4]. Compared with PET alone, using the CT component of hybrid PET/CT reduces false-positive interpretation of NaF uptake in benign lesions [3]. This raises the question as to whether the CT component of the PET/CT acquisition was used to full effect in the present study. The use of spinal MRI as a reference standard is also a possible limitation that is recognised by the authors, as this limits the comparison to only the spine, and MRI in itself is a method with known limitations. All patients had abnormal WBS for entry into the trial and whilst the PET methods were more sensitive on a lesion basis, a patient-based comparison was therefore not possible; however, the results imply that PET methods may identify metastatic disease in patients with normal WBS, as has been previously reported [3, 5].

Nevertheless, the authors should be congratulated in reporting valuable data from a prospective study where all imaging was performed in hormone-naïve patients, minimising confounding treatment-related effects, and within a small time window of 30 days; however, some questions remain. WBS is no longer state of the art for imaging the skeleton with radiolabelled bisphosphonates, such as ^99mTc-methylene diphosphonate (MDP). Although NaF PET/CT has been shown to be superior to planar WBS augmented with SPECT [3], there have not been head-to-head comparisons with ^99mTc-MDP SPECT/CT, where the potential advantages of the pharmacokinetics of NaF and the superior spatial resolution of PET compared with SPECT may not be as great. This may be particularly important given the difference in costs and availability of the two methods.

Despite the results from the present study, which show superiority of FCH PET/CT compared with NaF PET/CT with regard to specificity, taking the available literature as a whole, it remains unresolved as to what the best test for staging the skeleton in patients with high-risk prostate cancer should be at diagnosis. The different mechanisms of uptake of the PET tracers should be noted. NaF uptake reflects the local bone osteoblastic reaction to tumour within the bone marrow, whereas FCH uptake reflects metabolic activity within the tumour cells themselves. In prostate cancer, where the predominant effect is an increase in osteoblastic activity in the adjacent bone, the bone-specific tracers such as ^99mTc-MDP and NaF have shown high sensitivity; however, direct imaging of tumour cell metabolism, such as increased choline kinase activity and cell membrane synthesis with FCH, may be advantageous in detecting metastases in the bone marrow before an osteoblastic reaction has occurred [6]. It is possible that both PET tracers may be required to provide optimum diagnostic accuracy and of course FCH PET/CT also provides valuable data on nodal and visceral metastatic disease. In patients with recurrent disease, better specificity has been reported with FCH [4], NaF possibly being limited by non-specific treatment-related effects such as osteoblastic flare. For similar reasons it may be that the more tumour-specific imaging methods, such as FCH PET/CT or diffusion-weighted MRI, may be better in assessing the treatment response of skeletal metastases. Questions therefore remain as to the best imaging test at different times in the management of patients with metastatic prostate cancer. ^99mTc-MDP SPECT/CT deserves a full assessment, but perhaps the recent advent of PET/MRI and the potential synergies available from this hybrid technique may help resolve some of the remaining issues.

Gary Cook*† and Vicky Goh*‡

*Division of Imaging Sciences and Biomedical Engineering, King’s College London, † Clinical PET Centre, and ‡ Department of Radiology, Guy’s and St Thomas’ Hospitals NHS Foundation Trust, London, UK

References

1 Poulsen MH, Petersen H, Høilund-Carlsen PF et al. Spine metastases in prostate cancer: comparison of [99mTc]MDP wholebody bone scintigraphy, [18F]choline PET/CT, and [18F]NaF PET/CT. BJU Int 2014; 114: 818–23

2 Fogelman I, Blake GM, Cook GJ. The isotope bone scan: we can do better. Eur J Nucl Med Mol Imaging 2013; 40: 1139–40

3 Even-Sapir E, Metser U, Mishani E et al. 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: 287–974

4 Langsteger W, Balogova S, Huchet V et al. Fluorocholine (18F) and sodium fluoride (18F) PET/CT in the detection of prostate cancer: prospective comparison of diagnostic performance determined by masked reading. Q J Nucl Med Mol Imaging 2011; 55: 448–57

5 Kjölhede H, Ahlgren G, Almquist H et al. Combined 18F-fluorocholine and 18F-fluoride positron emission tomography/computed tomography imaging for staging of high-risk prostate cancer. BJU Int 2012; 110: 1501–6

6 Beheshti M, Vali R, Waldenberger P et al. Detection of bone metastases in patients with prostate cancer by 18F fluorocholine and 18F fluoride PET-CT: a comparative study. Eur J Nucl Med Mol Imaging 2008; 35: 1766–74