Results of this pilot study show the potential of PET-CT imaging of AS activity. Targeting of bone formation appears to be the most promising approach to visualize AS activity. Inflammation tracers ([18F]FDG and [11C](R)PK11195) seem to be less useful for imaging of AS than for imaging of active RA [16, 22–24].
There may be several explanations for the discrepancy between [18F]FDG, [11C](R)PK11195, and [18F]fluoride PET-CT findings. First of all, since the definite pathogenesis of AS still has to be elucidated, it is unknown which target site for imaging of AS is optimal . Entheses are of special interest, and synovitis seems to be less prominent in AS compared with RA . In addition, syndesmophyte formation and ankylosis, hallmarks of AS, reflect local osteoblastic activity. Our PET-CT findings suggest that bone formation (for example, osteoblastic activity) may be a more prominent feature of AS activity than inflammation. The present PET-CT results with the different tracers, therefore, reveal interesting data that may provide insights into the pathogenesis of AS.
Secondly, tracer biodistribution may be related to varying tracer characteristics. Uptake mechanisms are different for each tracer. In (red) bone marrow, [11C](R)PK11195 PET scans showed a diffuse increased uptake pattern which could possibly overwhelm potential small focal activity spots in or around bone. [18F]FDG is probably a useful marker for synovitis [16, 22, 23] and osteomyelitis [31, 32] but may be less suited for detection of (non- or low-inflammatory) bone formation in AS [33–37]. In general, [18F]FDG seems to be more useful for detection of osteolytic than for osteoblastic lesions . [18F]Fluoride, on the other hand, reflects osteoblastic activity because of the tracer's uptake into hydroxyapatite crystals, which form the mineral fluoroapatite within bone, especially at sites of bone formation [27, 28, 39]. Our positive results with [18F]fluoride PET-CT in both vertebral column and SI joints of patients with AS correspond with [18F]fluoride PET-CT findings of Strobel and colleagues  in SI joints of patients with AS and osteo-articular [18F]fluoride findings of Ben Ali and colleagues , indicating that [18F]fluoride is a potential tracer for active bone sites in AS.
A third explanation for the differences in uptake of the three tracers might be related to patient selection. Patients were categorized in low or high disease activity group according to the BASDAI level. BASDAI is a patient questionnaire commonly used to assess disease activity in AS. Congruent imaging results (no active lesions) were found in four out of five patients with low disease activity, corresponding to BASDAI measurements. In contrast, in patients with high disease activity (BASDAI ≥ 4), three out of seven patients with AS did not show any active inflammation on MRI. This corresponds to findings of others who did not find any association between MRI and clinical data [41, 42]. Therefore, high BASDAI scores with negative MRI may be more related to secondary degenerative changes and ankylosis rather than active inflammation. This is supported by the finding that six out of seven patients with high disease activity showed bony structural lesions in one or more vertebral bodies; at least 50% of these lesions had degenerative characteristics. Indeed, nowadays, the BASDAI is criticized, and recent studies express the belief that the ankylosing spondylitis disease activity score (ASDAS) is a better selection criterion than BASDAI [43–45]. Furthermore, NSAIDs were continued if used at inclusion. In theory, NSAID use may have suppressed inflammatory activity; however, Gaspersic and colleagues  showed that anti-inflammatory drugs have no influence on monitoring AS with MRI. In our study, NSAIDs did not seem to influence [18F]fluoride uptake in active lesions since PET-CT scans depicted 17 hotspots in the two patients scanned with this tracer.
PET-CT data were compared with MRI and conventional radiographs as references. Focusing on the two patients additionally scanned with [18F]fluoride PET-CT, most MRI lesions corresponded to lesions with [18F]fluoride uptake on the PET scan. Additionally, two active [18F]fluoride PET-CT lesions in SI joints showed subchondral fatty marrow infiltration on MRI. Although the exact significance of subchondral fatty marrow infiltration is not yet clear, it is believed to be a late structural change due to chronic inflammation in AS .
On the other hand, in 11 out of 17 [18F]fluoride PET-positive lesions, structural changes were found on conventional x-rays. (Secondary) degenerative changes such as sclerosis and facet arthrosis may result in a positive [18F]fluoride signal. However, these lesions could also reflect chronic AS disease activity (the mean symptom duration of patients 11 and 12 was 22 years). Indeed, degenerative changes as well as other structural changes such as squaring and syndesmophyte formation can coexist with chronic inflammation . Finally, the observed [18F]fluoride hotspots in the sternum and shoulder seemed to correlate with clinical symptoms of patients, again underlining the potential of [18F]fluoride PET-CT to visualize active sites in AS.