Response of bone metastases after treatment with ¹⁷⁷Lu-octreotate can be evaluated efficiently by SRS or ⁶⁸Ga-somatostatin PET [13]. Interestingly, in a recent study, it has been suggested that successful treatment of bone metastases can represent as lesions that increase in size on CT as a result of the repair process while showing a decrease in labeled somatostatin uptake [14].

¹⁸F-fluoride is a PET bone-seeking agent with uptake mechanism similar to that of the single-photon emitting tracer ⁹⁹mTc-MDP. Fluoride ions exchange with hydroxyl groups in hydroxyapatite crystal bone to form fluoro — apatite, and are deposited at the bone surface where bone turnover is greatest. Similar to ⁹⁹mTc-MDP, accumulation of ¹⁸F-fluoride uptake in bone metastases reflects increased regional blood flow and high bone turnover. ¹⁸Ffluoride has better pharmacokinetic characteristics compared with those of ⁹⁹mTc-MDP. The bone uptake of the former is twofold higher, and in contrast to ⁹⁹mTc-MDP it does not bind to protein. The capillary permeability of ¹⁸F-fluoride is higher and its blood clearance is faster, resulting in a better target-to-background ratio. Regional plasma clearance of ¹⁸F-fluoride is reported to be three to ten times higher in bone metastases compared with that in normal bone [15, 16]

¹⁸F-fluoride PET is very sensitive for detection of osteoblastic metastases and also lytic metastases, as the latter, even when considered “pure lytic”, do have minimal osteoblastic activity, which is enough for detection by ¹⁸F-fluoride PET. It should be borne in mind that ¹⁸F-fluoride is not tumor specific and therefore is a sensitive modality for detection of any bone abnormalities, not only malignant abnormalities.

When interpreting ¹⁸F-fluoride PET-CT for assessment of metastatic skeletal spread, the morphologic appearance of the bone should be carefully considered on the CT data, in order to accurately separate benign and malignant sites of ¹⁸F-fluoride uptake [17].

Several clinical reports in various malignancies have illustrated the superiority of ¹⁸F-fluoride PET-CT over BS for detection of bone metastases, with an excellent negative predictive value [18–21]. In patients with prostate cancer, ¹⁸f-Fluoride PET-CT showed a greater sensitivity than ¹⁸F-fluorocholine in the detection of bone metastasis, although the differences were not statistically significant [22]. In patients with lung cancer, it was found to be complementary to ¹⁸F-FDG PET-CT mainly for detection of sclerotic type abnormalities [23].

There are early data suggesting that ¹⁸F-fluoride PET can be used to assess treatment response in metastatic prostate cancer. PET was performed 6 and 12 weeks after treatment with Alpharadin® in a small pilot study of patients with prostate cancer. Measurement of serial standard uptake values allowed separation of responders and nonresponders [24].

However, use of ¹⁸F-floride PET is not yet routine. There is a multicenter study underway in the USA to assess the use of this modality in routine use of skeletal staging in cancer, comparing ¹⁸F-fluoride PET-CT with MDP bone scintigraphy in 500 patients with breast, prostate and non-small-cell lung cancer.