A Series Of Studies On The Application Of ⁶⁸Ga-FAPI In Periprosthetic Joint Infection

Objective:The diagnosis of periprosthetic joint infection（PJI）has always been the focus of orthopaedists.The existing PJI models have obvious limitations,in addition,studies of PJI on animal models using PET/CT for diagnosis are still lacking.Thus,the aim of this study was to establish a new PJI model and a loosening model and ¹⁸F-flurodeoxyglucose（FDG）and⁶⁸Ga-fibroblast activation protein inhibitor（FAPI）were employed to study their performance in these models.In addition,although ¹⁸F-FDG PET/CT has been reported in PJI,yet there are few reports on the characteristics of ¹⁸F-FDG PET/CT after hip arthroplasty.Therefore,we also intend to conduct a retrospective analysis of ¹⁸F-FDG PET/CT images of hip arthroplasty patients and to summarize some useful findings for clinical practice.Finally,⁶⁸Ga-FAPI PET/CT were performed in symptomatic hip arthroplasty patients and diagnostic criteria were established according to the uptake pattern.The PJI were diagnosed by SUVmax（maximum standardized uptake value）and uptake pattern and the application of radiomics in PJI was attempted.Methods:1、A novel PJI model of rabbit was developed by placing two screws in the tibia and femur.Based on bacteria concentration,the animals were divided into five groups,control,10⁴,10⁵,10⁶ and 10⁷.¹⁸F-FDG and ⁶⁸Ga-FAPI PET/CT were performed continuously in the next two weeks and maximum standardized uptake value（SUVmax）,mean standardized uptake value（SUVmean）,metabolic target volume（MTV）and total lesion glycolysis（TLG）/total lesion fibrosis（TLF）were calculated as the metrics.Meanwhile,serology,physical examination,gross examination and bacterial quantitation of both screw and knee joint were also performed as indexes.2、After surgery,the rabbits were divided into four groups,six in the control group and 10 in the loosening,S.aureus and S.epidermis groups.PET/CT and serological examination were performed every two weeks for three times.After sacrificed,micro-CT,tissue culture,pullout test and scanning electron microscope were performed.3、¹⁸F-FDG PET/CT images of hip arthroplasty patients were collected from September,2009 to August,2021.View of interest was outlined by two independent physicians and the results of SUVmax were recorded and compared.At the same time,the serological data were collected and the correlation between SUVmax and serological results was analyzed and the images were classified according to the diagnostic criteria proposed by Reinartz et al.Meanwhile,the interval between hip replacement and examination was classified by one year and the characteristics of the two groups were compared.Finally,the images of patients who underwent multiple examinations were analyzed dynamically.4、Patients with pain due to hip arthroplasty from December 2021 to January 2022 were collected and ⁶⁸Ga-FAPI PET/CT were performed.Reference standard was based on 2018Evidence-Based and Validation Criteria or follow-up of half year.The accuracy of SUVmax and uptake pattern was recorded and compared with preoperative diagnosis and final diagnosis.Meanwhile,original data were imported into IKT-snap to draw the view of interest,PHIgo was used to extract feature of clinical cases and cluster analysis was applied according to the groups.Results:1、As for weight change,control group was significantly smaller than other groups in the first and second week（P<0.05）,while the change of knee width of the 10⁷ group was clearly larger than that of the other group in the first and second week（P<0.05）.There was a clear trend that as the concentration of bacteria increased,so did the score for gross examination.As for SUVmax,all data of ¹⁸F-FDG were larger than that of ⁶⁸Ga-FAPI in the same group for both weeks.For the performance of ¹⁸F-FDG,there was no definitive conclusion could be drawn for SUVmax and SUVmean.As far as ⁶⁸Ga-FAPI was concerned,10⁴ group was significantly larger than 10⁵,10⁶ and 10⁷ groups for SUVmax and SUVmean in both weeks（P<0.05）.And MTV of ⁶⁸Ga-FAPI was found to be almost always larger than that of ¹⁸F-FDG in the same group.2、As for ¹⁸F-FDG,performances of control and loosening groups were similar.SUVmax of S.aureus had been consistently in the high range than that of S.epidermis.As for ⁶⁸Ga-FAPI,control group had the lowest SUVmax in the second week and increased gradually.SUVmax of loosening group began exceed control group since the second week.SUVmax of S.aureus in the second week was the lowest among four group and raised as the number of weeks increased and equalled to SUVmax of S.epidermis in the sixth week.Linear regressions between SUVmax and serology showed that ¹⁸F-FDG was positively correlated with CRP and IL-6 while ⁶⁸Ga-FAPI revealed negative and positive correlation with CRP and IL-6 in the second and sixth week.Besides,both SUVmax and MTV of ¹⁸F-FDG or ⁶⁸Ga-FAPI were negatively correlated with BV/TV and BS/TV.3、A total of 121 examinations were included,including six patients underwent 2 times and2 patients went 3 times.There was no significant correlation between SUVmax and serological results.The agreement between the two physicians in classifying according to the criteria proposed by Reinartz et al.was 0.957（P<0.005）.Although there was non-specific uptake in cases with a time interval of less than one year,this uptake was not significant.In addition,the ¹⁸F-FDG demonstrated its potential application in the dynamic observation of hip conditions.4、A total of 43 patients were included and 15 of them were PJI.The area under curve of SUVmax was 0.8750,which was better than all of the serological tests.The cut-off value of SUVmax was 7.555 and the sensitivity and specificity were 67.86%and 100%respectively.The sensitivity,specificity and accuracy of uptake pattern were 100%,92.86%and 95.35%.In radiomics analysis,clinical cases were divided into PJI and non-infected hip arthroplasty failure.And the features of PJI were significantly different from non-infected hip arthroplasty failure.Conclusion:1、The performance and mechanism of ⁶⁸Ga-FAPI is totally different from ¹⁸F-FDG and this unique property of ⁶⁸Ga-FAPI shows a promising application prospect in detecting infection boundary and may even distinguish a small number or a large number of bacterial infections.Related research is urgently needed.2、In this longitudinal observation,⁶⁸Ga-FAPI showed greater sensitivity than ¹⁸F-FDG in detecting diseases,and ⁶⁸Ga-FAPI had not intestinal and muscular uptake.MTV of ⁶⁸Ga-FAPI were larger than ¹⁸F-FDG,which meant that ⁶⁸Ga-FAPI had the potential to define the scope of lesions more accurately.Finally,SUVmax could not differentiate loosening and infection in⁶⁸Ga-FAPI,further study about diagnostic criteria was warranted.3、SUVmax could provide information independent of serological results,meanwhile,¹⁸F-FDG also showed a certain potential application in dynamic observation of hip arthroplasty related diseases.However,the appearance of blood vessels,muscle,bone marrow and so on affected the image judgment in a certain extent and the specificity of ¹⁸F-FDG was not ideal.On the premise of maintaining the original superiority of PET/CT,a more specific radionuclide is worth a try.4、The efficiency of ⁶⁸Ga-FAPI PET/CT in diagnosing PJI was ideal and diagnostic criteria of uptake pattern were more clinically instructive.And radiomics also showed a certain application prospect in the field of PJI.