Background/Purpose:

To use in vivo multimodal [¹⁸F]FDG (fluoro-D-glucose, tracer for inflammation) and [¹⁸F]Sodium Fluoride (bone tracer) positron emission tomography/computed tomography (PET-CT) imaging for the monitoring of systemic inflammatory and bone remodeling processes as well as colocalized bone destructions before and after TNF blockade in human tumor necrosis factor transgenic (hTNFtg) mice, an established mouse model of chronic inflammatory, erosive polyarthritis.

Methods:

8 week-old hTNFtg mice were treated with anti-TNF antibodies (Infliximab, i.p., 3x times per week, 10mg/kg body weight) for 4 weeks. Before and after the treatment period mice received [¹⁸F]FDG or [¹⁸F]Sodium Fluoride (~25MBq) static PET scans (45min post injection) followed by whole-body and high resolution leg CT scans (800kV, 500µA, 800ms, 360 projections) using an Inveon PET/CT/SPECT multimodality system (Siemens Medical Solutions). PET reconstructions were conducted with OSEM3D/MAP, FBP algorithm. Standard uptake values (SUV) were calculated using PMOD software. Radiographic damage score was evaluated by in vivo CTs using InveonResearchWorkplace software. Joints were further analyzed by ex vivo µCT scans (Scanco µCT35) and H&E, TRAP and TB stained paraffin-sections.

Results: Before therapeutic intervention, we observed an increased accumulation of [¹⁸F]FDG in various joints of hTNFtg mice including knees, ankles and shoulders compared to wt littermates indicating ongoing systemic inflammatory processes. Moreover, existing bone destructions were detected by in vivoCTs. However, [¹⁸F]SodiumFluoride was equally accumulated within bone tissues such as long bones, in particular at growth plates, and vertebrae between both genotypes. After four weeks, placebo-treated hTNFtg animals showed significantly increased [¹⁸F]FDG SUVs as well as progressive bone destruction in knees, ankles and shoulders as shown by in vivoCTs. In contrast, TNF-blockade led to a significant decrease in [¹⁸F]FDG SUVs supposing complete resolution of inflammatory processes in those individuals. Comparison of repeated in vivoCT images demonstrated a significant reduction in radiographic bone damage score and reversal of existing bone destructions upon TNF blockade. Histological analysis demonstrated regeneration processes of former bone erosion sites present as refillings of cartilaginous or fibro-cartilaginous tissue as well as signs of endochondral ossifications or even intact bone surfaces upon TNF blockade. Surprisingly, we found no marked changes in [¹⁸F]Fluoride SUVs in joints between both hTNFtg groups and wt mice suggesting that age-related high [¹⁸F]Fluoride accumulations in growth plates interfere, thus preventing to monitor inflammatory bone damage.

Conclusion: In vivo small animal multimodal [¹⁸F]FDG, but not [¹⁸F]Fluoride, PET-CT imaging provides an objective, non-invasive imaging tool for the longitudinal monitoring of (I) reversibility of ongoing inflammatory processes in various joints and (II) regeneration of existing bone erosions during therapeutic intervention in TNF-driven experimental arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/resolution-of-systemic-joint-inflammatory-processes-and-regeneration-of-existing-bone-damage-upon-tnf-blockade-as-monitored-by-in-vivo-multimodal-pet-ct-imaging-in-progressed-experimental-arthritis/