Potential usefulness of 68Ga-citrate PET/CT in detecting infected lower limb prostheses

Abstract

Background: Prosthetic joint infections may lead to failures of total joint arthroplasty. Radionuclide imaging can play a diagnostic role in identifying such infections, which require two-stage exchange arthroplasty (instead of simple revision surgery performed in non-infected cases). Although ¹⁸F-FDG PET/CT has emerged as a novel diagnostic tool in this setting, the clinical usefulness of ⁶⁸Ga-citrate PET/CT has not been previously investigated. This single-center prospective study was designed to address this issue.

Methods: Between January 2016 and October 2017, we examined 34 patients with clinically proven or suspected prosthetic hip/knee joint infections scheduled to undergo surgery. All patients underwent ⁶⁸Ga-citrate PET/CT scans and sequential ¹⁸F-FDG PET/CT imaging for comparative purposes. Intraoperative findings and the results of microbiological analyses of surgical specimens served as gold standard. The diagnostic results were examined according to (1) image interpretation based on radiotracer uptake patterns and (2) quantitative analysis using volumes of interest (VOIs) to calculate standard uptake values (SUVs) and metabolic volumes (MVs).

Results: A total of 26 (76%) patients were diagnosed as having infections. Based on radiotracer uptake pattern criteria, the sensitivity, specificity, and accuracy of ⁶⁸Ga-citrate PET/CT and ¹⁸F-FDG PET/CT were 92%, 88%, and 91% and 100%, 38%, and 85%, respectively. MV was significantly higher in the infected group when ⁶⁸Ga-citrate PET/CT was used (422.45 vs. 303.65 cm³, p = 0.027), whereas no significant differences were observed on ¹⁸F-FDG PET/CT. According to receiver operating characteristic (ROC) curve analysis, a cut-off value of 370.86 for MV resulted in a sensitivity of 61.5% and a specificity of 87.5% (area under curve: 0.75, 95% confidence interval: 0.57-0.88, p = 0.035).

Conclusions: Subject to future confirmation, our data provide preliminary evidence that ⁶⁸Ga-citrate PET/CT may have a complimentary role to ¹⁸F-FDG PET/CT in detecting prosthetic joint infections, being characterized by a higher specificity and the possibility to discriminate between an infectious condition and sterile inflammation.

Trial registration: This prospective study was registered at clinicaltrials.gov (registration number: NCT02855190 ).

Keywords: 18F-FDG; 68Ga-citrate; PET/CT; Prosthetic joint infections.

Fig. 1

Patient (case # 16) with a history of right total hip arthroplasty performed 16 years before imaging. The results of ¹⁸F-FDG PET/CT (upper row) and ⁶⁸Ga-citrate PET/CT (lower row) are presented. a–d Green arrows indicate an intense ¹⁸F-FDG uptake surrounding the cup and the proximal part of the hip prosthesis stem components. On CT images, osteolytic changes and the presence of residual cement in the right acetabulum were evident. Cup loosening with synovial hypertrophy and clear joint fluid were detected during surgery. ¹⁸F-FDG PET/CT findings were therefore classified as false positve. d–f Findings on ⁶⁸Ga-citrate PET/CT were true negative, without any obvious radiotracer accumulation at the corresponding sites. h Plain film

Fig. 2

Patient (case # 1) with a history of right hip prosthesis implantation performed 7 months before imaging. The results of ¹⁸F-FDG PET/CT (upper two rows) and ⁶⁸Ga-citrate PET/CT (lower two rows) are presented. a–f The red arrows clearly indicate ¹⁸F-FDG uptake occurring at the sinus tract, which was absent on the corresponding ⁶⁸Ga-citrate PET/CT image. There was also evidence of swollen periarticular soft tissue (blue arrows) at the right ischiofemoral space on CT, which was accompanied by an increased ¹⁸F-FDG uptake. A similar pattern of radiotracer uptake (b, h) was found to occur at the bone-prosthesis interface of the stem component, as well as in the adjacent soft tissue. The imaging results were considered positive, and the case was subsequently classified as true positive. g–l The green arrows indicate an increased ⁶⁸Ga-citrate uptake occurring at the left femoral shaft. The CT scan revealed cortical hypertrophy caused by a prior traumatic fracture followed by bone reunion

Fig. 3

Patient (case # 14) with a history of hip prosthesis implantation performed 8 months before imaging. The results of ¹⁸F-FDG PET/CT (upper row) and ⁶⁸Ga-citrate PET/CT (lower row) are presented. a–d The green arrows indicate an increased ¹⁸F-FDG uptake occurring in necrotic tissue located within a swollen left quadratus femoris muscle. There was also evidence of an increased ¹⁸F-FDG uptake occurring at the bone-prosthesis interface (cup component; blue arrow). Taken together, these findings were suggestive of an infectious process which was confirmed intraoperatively (presence of cloudy synovial fluid and necrotic tissue). e–h The blue arrows indicate an increased ⁶⁸Ga-citrate uptake occurring at the bone-prosthesis interface (especially in the proximal portion). An osteolytic change in the anterior cortex of the left femur was observed on a CT image, accompanied by an increased ⁶⁸Ga-citrate uptake (which was present in the adjacent bone marrow as well, red arrows)

Fig. 4

Patient (case # 3) with a history of knee prosthesis implantation performed 12 months before imaging. The results of ¹⁸F-FDG PET/CT (upper row) and ⁶⁸Ga-citrate PET/CT (lower row) are presented. a–d The green arrows indicate an increased ¹⁸F-FDG uptake at both the bone prosthesis interface and the knee synovium. e–h A similar pattern of ⁶⁸Ga-citrate uptake was evident. The imaging results were considered positive, and the case was subsequently confirmed as true positive. d, h In contrast to the femoral portion, there was no increased radiotracer uptake along the bone prosthesis interface of the elongated tibial stem component (indicating no loosening or infection of a specific prosthesis segment, blue arrows)

Fig. 5

Scatter diagrams for a SUV_mean, b SUV_max, and c metabolic volume. Dots and triangles represent ¹⁸F-FDG PET/CT and ⁶⁸Ga-citrate PET/CT data, respectively. Bars represent mean values ± standard deviations