Pilot study on <sup>18</sup>F‐FDG PET/CT for detection of inflammatory changes in blood‐induced knee arthropathy in a rabbit model

Shammas, Amer; Doria, A.; Amirabadi, Afsaneh; Gahunia, Harpal K.; Jong, Roland; Charron, Martin; Moineddin, Rahim; Metser, Ur

doi:10.1111/hae.13090

Cited by 3 publications

(5 citation statements)

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“…As described in previous studies [18, 28, 34, 35], for 8 weeks, intra-articular autologous blood injections were administered twice per week to create mild arthropathy in both knees of each rabbit in Group A. Intra-articular autologous blood injections were administered twice per week for 16 weeks to create severe arthropathy in both knees of each rabbit in Groups B and C (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

“…To create this rabbit model of hemophilic arthropathy, we collected 2.5 mL of autologous blood without anticoagulants after establishing vascular access through the marginal vein in each rabbit's ear with a 26-gauge peripheral venous catheter. The collected 2.5 mL of autologous blood was divided into two, and 1.25 mL of blood was injected into the lateral joint space of each knee as described [28,35].…”

Section: Experimental Design and Animalsmentioning

confidence: 99%

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What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

Mert

Bılgıç

Şenol

et al. 2023

Clin Orthop Relat Res

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Background Hemophilic arthropathy can cause recurrent hemarthroses and severe damage to the synovium and articular cartilage. Previous studies have shown that vascular endothelial growth factor (VEGF) plays an essential role in neoangiogenesis. Bevacizumab, a monoclonal VEGF inhibitor, is used clinically to prevent angiogenesis. However, its effects on hemophilic arthropathy are unknown. Questions/purposes Using a hemophilic arthropathy rabbit model, we asked: Does an intra-articular injection of bevacizumab (1) inhibit VEGF, (2) decrease signal intensity in dynamic contrast-enhanced MRI (DCE-MRI) as an assessment of capillary permeability and neoangiogenesis, (3) reduce cartilage damage, (4) reduce synovial changes, and (5) affect macroscopic changes during the development of hemophilic arthropathy? Methods Twenty-five male New Zealand rabbits were divided into four groups. Eight knees from four rabbits were used as the control group. We used an established animal model for hemophilic arthropathy in the remaining 21 rabbits. Animals were assigned randomly to three groups with seven rabbits in each group. One group was used to establish mild arthropathy, and the other two were used to establish severe arthropathy. Autologous blood from the rabbits’ ears was injected into the right and left knees twice per week for 8 weeks to represent mild arthropathy and for 16 weeks to represent severe arthropathy. In the mild arthropathy group, bevacizumab was injected into the right knee once every 2 weeks. Bevacizumab was injected into the right knee of rabbits in one of the severe arthropathy groups once every 2 weeks for 16 weeks, and intra-articular bevacizumab injections were administered to the right knees of rabbits in the other severe arthropathy group once every 2 weeks after the eighth week. An equal volume of 0.9% saline was injected into the left knee of rabbits in all arthropathy groups. To explore the efficacy of bevacizumab, joint diameters were quantitatively measured, and cartilage and synovial changes were examined. Degeneration of articular cartilage was evaluated with the semiquantitative Osteoarthritis Research Society International grading system. Synovial damage was analyzed with a semiquantitative microscopic scoring system. In addition, we evaluated perfusion and angiogenesis using DCE-MRI (quantitative signal intensity changes). Immunohistochemical testing was used to measure VEGF levels (analyzed by Western blotting). Results Intra-articular bevacizumab treatment inhibited VEGF in our rabbit model of hemophilic arthropathy. VEGF protein expression levels were lower in the mild arthropathy group that received intra-articular bevacizumab (0.89 ± 0.45) than the mild arthropathy control group (1.41 ± 0.61) (mean difference -0.52 [95% CI -0.898 to -0.143]; p = 0.02). VEGF levels were lower in the severe arthropathy group that received treatment for 16 weeks (0.94 ± 0.27) than in the control knees (1.49 ± 0.36) (mean difference -0.55 [95% CI -0.935 to -0.161]; p = 0.01). In the severe arthropathy group, the Osteoarthritis Research Society International score indicating cartilage damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than in the control group (median 17 [range 13 to 18] versus 18 [range 17 to 20]; difference of medians 1; p = 0.02). Additionally, the scores indicated synovial damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than the control group (median 5 [range 4 to 9] versus 9 [range 8 to 12]; difference of medians 4; p = 0.02). The mean of mean values for signal intensity changes was higher in the nontreated severe groups than in the group of healthy knees. The signal intensity changes were higher in the severe arthropathy control groups (Groups BC and CC) (median 311.6 [range 301.4 to 361.2] and 315.1 [range 269.7 to 460.4]) than in the mild arthropathy control group (Group AC) (median 234.1 [range 212.5 to 304.2]; difference of medians 77.5 and 81, respectively; p = 0.02 and p = 0.04, respectively). In the severe arthropathy group, discoloration caused by hemosiderin deposition in the cartilage and synovium was more pronounced than in the mild arthropathy group. In the severe arthropathy group treated with intra-articular bevacizumab, joint diameters were smaller than in the control group (Group BT median 12.7 mm [range 12.3 to 14.0] versus Group BC median 14.0 mm [range 13.1 to 14.5]; difference of medians 1.3 mm; p = 0.02). Conclusion Hemarthrosis damages the synovial tissues and cartilage in the knees of rabbits, regardless of whether they are treated with intra-articular bevacizumab. However, intra-articular injection of bevacizumab may reduce cartilage and synovial damage in rabbits when treatment is initiated early during the development of hemophilic arthropathy. Clinical Relevance If the findings in this study are replicated in larger-animal models that consider the limitations of our work, then a trial in humans might be appropriate to ascertain whether intra-articular injection of bevacizumab could reduce cartilage damage and synovial changes in patients with hemophilia whose hemarthroses cannot otherwise be controlled.

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Section: Methodsmentioning

confidence: 99%

Section: Experimental Design and Animalsmentioning

confidence: 99%

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

Mert

Bılgıç

Şenol

et al. 2023

Clin Orthop Relat Res

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“…This study was approved by the ethical committee of the animal center of the Medical College of Soochow University. According to Shammas et al and Wang et al [13,14], 20 male SPF New Zealand rabbits (10 weeks of age) weighing 2.5-3.0 kg were used to establish the rabbit knee HA models. They were firstly anesthetized by 10% chloral hydrate solution.…”

Section: Establishment Of the Knee Ha Models Using New Zealand Rabbitsmentioning

confidence: 99%

“…Rabbits (n = 8) in the mild group were injected for 8 weeks whereas those (n = 8) in the severe group were injected for 16 weeks. The severe groups (n = 8) were firstly injected for 8 weeks, and then together with the mild groups underwent another 8 week of blood injection [13][14][15]. Therefore, rabbits in two groups were at the same age when processed for P-PRP treatment.…”

Section: Establishment Of the Knee Ha Models Using New Zealand Rabbitsmentioning

confidence: 99%

Pure platelet-rich plasma facilitates the repair of damaged cartilage and synovium in a rabbit hemorrhagic arthritis knee model

Xue

Jiang

et al. 2020

Arthritis Res Ther

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Objective: Hemorrhagic arthritis (HA) is a common disease of the musculoskeletal system caused by hemorrhage in the joints, leading to damages in the synovium and cartilage. Pure platelet-rich plasma (P-PRP) has been recently demonstrated to have anti-inflammatory and regenerative potential attributed to the various cytokines and growth factors that it contains. The aim of this study was to investigate the efficacy of P-PRP for the treatment of patients with mild and severe HA. Methods: Autologous blood was withdrawn from the New Zealand rabbits and injected into their left and right knees to establish the HA models. The injection was performed once a week and repeated for 8 weeks to establish the mild HA models and for 16 weeks to establish the severe HA models. One hundred microliters of P-PRP was injected into the left HA knees, and the same volume of sterile 0.9% saline was injected into the corresponding right knees. MRI examination, H&E staining, and toluidine blue staining were respectively performed to evaluate the histological difference of synovium and cartilage between the P-PRP treated and untreated mild and severe groups. Normal knees were set as the control group.

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“…12,13 There is preclinical data regarding the use of 18 F-FDG PET/CT in HA, which was reported by Shammas et al who used this modality to detect reactive inflammatory process of the joint and synovial tissues associated with HA in a rabbit model of blood-induced arthritis. 14 Given its utility in OA and RA, which share substantial pathological features with HA, we investigated the potential of 18 F-FDG PET/CT as a marker of inflammation to detect and quantify early HA changes.…”

Section: Introductionmentioning

confidence: 99%

¹⁸F‐FDG PET/CT imaging for haemophilic arthropathy compared with clinical, radiological and power Doppler sonographic characteristics of 20 haemophilia patients

Lin

Pan

et al. 2022

Haemophilia

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Introduction and objectives: Repeated joint bleeding in haemophilia patients may lead to haemophilic arthropathy with marked inflammation and synovitis.This study investigated the potential of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET/CT) as a novel diagnostic method for haemophilic arthropathy. Materials and methods:We recruited 20 adult haemophilia patients who reported history of hemarthroses in the shoulder, elbow, hip, knee, or ankle joints. All joints were assessed by power Doppler ultrasonography and radiography, and graded by hyperaemia score and Pettersson score, respectively. Joint pain was evaluated by visual analogue score (VAS). Range of motion (ROM), Haemophilia Joint Health Score (HJHS) and annual joint bleeding rate (AJBR) were recorded. Finally, all participants had whole-body 18 F-FDG PET/CT, and maximum standardized uptake value (SUVmax) of the joints being studied was measured.Results: Thirteen patients had severe haemophilia, and seven had moderate haemophilia. The mean age was 36 years. PET SUVmax showed significant correlations with VAS, ROM, Pettersson score, hyperaemia score, HJHS score and AJBR in all large joints except hip. Joints with pain, hyperaemia and radiographic changes were found to have higher SUVmax than those without these features. Using Youden's index, the optimal cut-off value for early radiographical arthropathy was found to be between 1.9 and 2.0. Conclusion:Our study indicates that 18 F-FDG PET/CT imaging correlated well with various conventional diagnostic techniques. It also demonstrated high sensitivity and specificity for early radiographic arthropathy. 18 F-FDG PET/CT imaging may quantitatively evaluate disease activity of most large joints in a single examination and help detect early haemophilic arthropathy.

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Pilot study on ¹⁸F‐FDG PET/CT for detection of inflammatory changes in blood‐induced knee arthropathy in a rabbit model

Abstract: F-FDG-PET is able to detect the inflammatory changes associated with haemophilic arthropathy in this experimental model.

Cited by 3 publications

References 29 publications

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

Pure platelet-rich plasma facilitates the repair of damaged cartilage and synovium in a rabbit hemorrhagic arthritis knee model

¹⁸F‐FDG PET/CT imaging for haemophilic arthropathy compared with clinical, radiological and power Doppler sonographic characteristics of 20 haemophilia patients

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Pilot study on 18F‐FDG PET/CT for detection of inflammatory changes in blood‐induced knee arthropathy in a rabbit model

Abstract: F-FDG-PET is able to detect the inflammatory changes associated with haemophilic arthropathy in this experimental model.

Cited by 3 publications

References 29 publications

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

Pure platelet-rich plasma facilitates the repair of damaged cartilage and synovium in a rabbit hemorrhagic arthritis knee model

18F‐FDG PET/CT imaging for haemophilic arthropathy compared with clinical, radiological and power Doppler sonographic characteristics of 20 haemophilia patients

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Pilot study on ¹⁸F‐FDG PET/CT for detection of inflammatory changes in blood‐induced knee arthropathy in a rabbit model

¹⁸F‐FDG PET/CT imaging for haemophilic arthropathy compared with clinical, radiological and power Doppler sonographic characteristics of 20 haemophilia patients