Application of 68Ga-citrate PET/CT for differentiating periprosthetic joint infection from aseptic loosening after joint replacement surgery

Abstract

Aims: We aimed to evaluate the utility of ⁶⁸Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with ^99mTc-methylene bisphosphonates (^99mTc-MDP) bone scan.

Methods: We studied 39 patients with suspected PJI or AL. These patients underwent ⁶⁸Ga-citrate PET/CT, ^99mTc-MDP three-phase bone scan and single-photon emission CT (SPECT)/CT. PET/CT was performed at ten minutes and 60 minutes after injection, respectively. Images were evaluated by three nuclear medicine doctors based on: 1) visual analysis of the three methods based on tracer uptake model, and PET images attenuation-corrected with CT and those not attenuation-corrected with CT were analyzed, respectively; and 2) semi-quantitative analysis of PET/CT: maximum standardized uptake value (SUVmax) of lesions, SUVmax of the lesion/SUVmean of the normal bone, and SUVmax of the lesion/SUVmean of the normal muscle. The final diagnosis was based on the clinical and intraoperative findings, and histopathological and microbiological examinations.

Results: Overall, 23 and 16 patients were diagnosed with PJI and AL, respectively. The sensitivity and specificity of three-phase bone scan and SPECT/CT were 100% and 62.5%, 82.6%, and 100%, respectively. Attenuation correction (AC) at 60 minutes and non-AC at 60 minutes of PET/CT had the same highest sensitivity and specificity (91.3% and 100%), and AC at 60 minutes combined with SPECT/CT could improve the diagnostic efficiency (sensitivity = 95.7%). Diagnostic efficacy of the SUVmax was low (area under the curve (AUC) of ten minutes and 60 minutes was 0.814 and 0.806, respectively), and SUVmax of the lesion/SUVmean of the normal bone at 60 minutes was the best semi-quantitative parameter (AUC = 0.969).

Conclusion: ⁶⁸Ga-citrate showed the potential to differentiate PJI from AL, and visual analysis based on uptake pattern of tracer was reliable. The visual analysis method of AC at 60 minutes, combined with ^99mTc-MDP SPECT/CT, could improve the sensitivity from 91.3% to 95.7%. In addition, a major limitation of our study was that it had a limited sample size, and more detailed studies with a larger sample size are warranted. Cite this article: Bone Joint Res 2022;11(6):398-408.

Keywords: 68Ga-citrate; 99mTc-MDP; Aseptic loosening; PET/CT; Periprosthetic joint infection; aseptic loosening; bisphosphonates; bone scan; hip; joint replacement surgery; knee; lesions; periprosthetic joint infection (PJI); positron emission tomography; single-photon emission computed tomography.

Fig. 1

The receiver operating characteristic curves of maximum standardized uptake value (SUVmax) of lesions, SUVmax of the lesion/SUVmean of the normal bone, and SUVmax of the lesion/SUVmean of the normal muscle. T/NT, SUVmax of target region/SUVmean of non-target region.

Fig. 2

Positive findings for infection in the three-phase bone scan, single-photon emission CT (SPECT)/CT, and positron emission tomography (PET)/CT in a patient with periprosthetic joint infection (PJI) confirmed by microbiological culture of Staphylococcus aureus and Escherichia coli. A 46-year-old woman underwent right hip arthroplasty for traumatic osteoarthritis in 2018, and developed pain in the right hip joint in April 2020. a) and b) Anteroposterior (AP) and lateral radiographs of the right hip joint at two years postoperatively showed an uneven decrease in bone density around the prosthesis. c) to e) ^99mTc-MDP three-phase bone scan showed positive perfusion, blood pool, and delayed phase in the right hip (arrowheads) (red circles of c) to d) – region of interest of the affected side; yellow circles of c) to d) – region of interest of the normal side). f) and g) SPECT/CT revealed a diffuse increase in bone metabolism in the femoral prosthesis (arrowheads). h) to l) ⁶⁸Ga-citrate PET/CT showed uneven diffuse uptake of the right femur trochanter around the soft-tissue and the distal femoral prosthesis (arrowheads). The patient underwent surgical treatment, and a large amount of pus was found in the right hip joint. m) and n) Histopathological examination revealed many neutrophils, lymphocytes, and plasma cells (haematoxylin and eosin (H&E) 200×). Microbial culture showed the presence of Staphylococcus aureus and Escherichia coli. PJI of the right hip was diagnosed.

Fig. 3

True positive findings in three-phase bone scan and positron emission tomography (PET)/CT, and false negative findings for infection in single-photon emission CT (SPECT)/CT, in a patient with periprosthetic joint infection (PJI) caused by Staphylococcus epidermidis. A 66-year-old man underwent right knee arthroplasty for osteoarthritis (OA) in December 2019, and he developed pain and exudate in the right knee in March 2020. Further, physical examination showed swelling of the right knee joint, with a sinus tract that communicated with the prosthesis. a) and b) Anteroposterior (AP) and lateral radiographs of the right knee joint at three months postoperatively showed obvious swelling of the right knee joint and an uneven decrease in bone density around the prosthesis. The patient was diagnosed with PJI, considering the above symptoms. The patient was included in our prospective study, and he signed an informed consent form for further imaging. c) to e) ^99mTc-MDP three-phase bone scan showed positive perfusion, blood pool, and delayed phase in the right knee (arrowheads) (red circle and region of interest of the affected side (ROIA); yellow circle and region of interest of the normal side (ROIB)). f) and g) SPECT/CT revealed focal increased bone metabolism at the right patella-prosthesis interface (arrowheads), and e) and f) the uniform and symmetrical uptake distributed along the edge of tibial and femoral component was regarded as non-specific uptake (dotted arrows). In addition, e) and g) show that focal uptake with hyperosteogeny was found on the medial articular surface of the left knee, which was considered to be OA (arrows). h) to l) ⁶⁸Ga-citrate PET/CT showed an obvious diffuse uptake around the right knee prosthesis (arrowheads). h), j), and l) PET/CT also showed a focal uptake in the left knee joint, which was consistent with the findings of SPECT/CT (arrows). Subsequently, the patient underwent surgical treatment. m) and n) Histopathological examination showed the presence of acute suppurative inflammation (m, haematoxylin and eosin (H&E) 100×; n, H&E 400×). Staphylococcus epidermidis was found in three of the five samples.

Fig. 4

True positive findings in the three-phase bone scan and single photon emission CT (SPECT)/CT, and false negative findings in positron emission tomography (PET)/CT, for infection in a patient with periprosthetic joint infection (PJI) confirmed by microbiological culture of Enterobacter faecalis. A 59-year-old man underwent a right hip arthroplasty for traumatic arthritis of the right hip after fracture of the right femur in 2012. Further, he underwent revision surgery for aseptic loosening (AL) of the right hip joint in 2019. He developed pain and swelling of the right hip joint one month ago. a) and b) No obvious positive signs were found in the anteroposterior (AP) and lateral radiographs postoperative at one year of the right hip joint. c) to e) ^99mTc-MDP three-phase bone scan showed positive perfusion, blood pool, and delayed phase in right hip (arrows) (red circle and region of interest of the affected side (ROIA); yellow circle and region of interest of the normal side (ROIB)). f) and g) SPECT/CT revealed diffusely increased bone metabolism at the right acetabulum-prosthesis interface (arrows). h) to l) ⁶⁸Ga-citrate PET/CT showed no abnormal focal or diffuse uptake (arrows). Subsequently, the patient underwent surgical treatment. m) and n) Histopathological examination of synovial tissue showed chronic inflammatory changes (haematoxylin and eosin (H&E) 400×). However, Enterobacter faecalis was found in two of the five samples. PJI of the right hip was diagnosed.

Fig. 5

False positive findings in three-phase bone scan and true negative findings in single-photon emission CT (SPECT)/CT and positron emission tomography (PET)/CT in a patient with aseptic loosening (AL). A 66-year-old man underwent left knee arthroplasty for traumatic osteoarthritis of the left knee after fracture of the left femur in 2009, and he developed pain in the left knee joint one week ago. a) and b) No obvious positive signs were found in the anteroposterior (AP) and lateral radiographs postoperative at ten years of the left knee joint. c) to e) ^99mTc-MDP three-phase bone scan showed positive perfusion, blood pool, and delayed phase in the left knee (arrows) (red circles of c) to d) – region of interest of the affected side; yellow circles of c) to d) – region of interest of the normal side). f) and g) SPECT/CT revealed several points of focally increased bone metabolism at the bone-prosthesis interface of the left knee (arrows). h) to l) ⁶⁸Ga-citrate PET/CT showed mild uptake distributed uniformly and symmetrically along the edge of the prosthesis (arrows). The patient then underwent surgical treatment, and a large amount of proliferated synovial tissue was found; the prosthetic joint was obviously loose. m) and n) Histopathological examination showed proliferative fibrous connective tissue (haematoxylin and eosin (H&E) 400×). The postoperative microbial cultures were both negative. The patient was diagnosed with AL.