The Use of ^99mTc-Recombinant Human Annexin V Imaging for Differential Diagnosis of Aseptic Loosening and Low-Grade Infection in Hip and Knee Prostheses

Abstract

The aim of this study was to assess the pattern of annexin V uptake in hip and knee prostheses suspected of being infected. Methods: A total of 7 patients undergoing revision surgery for hip or knee prostheses were studied; 5 patients had total hip replacements, and 2 had total knee replacements. Infection was confirmed by pathology, culture results, laboratory evaluation, and clinical follow-up. All patients also underwent a bone scan before surgery. Results: Annexin V scan findings were positive in 5 patients and negative in 2. Annexin V uptake was either focal (n 5 4) or linear (n 5 1). There were 4 true-positive, 2 true-negative, 1 false-positive, and no false-negative annexin V studies. Annexin V uptake was either more extensive or less extensive than, and usually was incongruent with, 99m Tc-methylene diphosphonate uptake. Conclusion: Our findings suggest that annexin V imaging shows greater uptake with infection than with aseptic loosening and has a high negative predictive value for prosthetic infection.Key Words: apoptosis; annexin V; hip; knee; prosthesis; loosening; infection Nucl Med 2009; 50:534-537 DOI: 10.2967/jnumed.108.059345 Asept ic loosening, an event that occurs months to years after surgery, is the most frequent cause of prosthetic joint failure (1). A less common but far more serious source of joint implant loosening is periprosthetic infection with Staphylococcus aureus, methicillin-resistant S. aureus, Staphylococcus epidermidis, Streptococcus oralis, Escherichia coli, Enterococcus faecalis, or Pseudomonas aeruginosa (2). Periprosthetic infections also tend to be low-grade and frequently cannot be detected by blood or tissue culture, leaving little clinical information to guide treating physicians. The differentiation of infection from aseptic loosening is important because loosening caused by a periprosthetic infection requires usually at least a 2-stage revision surgery involving the removal of the old implant, debridement, and placement of antibiotic-loaded cement beads in the surgical bed. This treatment is in contrast to the single-stage prosthetic joint-replacement treatment for aseptic loosening, a completely different process believed to be caused by repeated mechanical stress and local host response to the wear debris of high-density polyethylene, metals, and bone cement (1). JBecause the clinical and laboratory signs of bacterial infection (culture-negative) are nonspecific, standard radiologic and nuclear medicine imaging remain essential first steps for the work-up of patients with painful prostheses (3). Radiographs reveal signs of loosening regardless of the presence or absence of bacterial infection. Although MRI or enhanced CT scans generally provide useful information for soft-tissue and bone infections, metallic artifacts from a given prosthetic device greatly interfere with the quality of the images obtained (4). Nuclear medicine techniques include 99m Tc-methylene diphosphonate ( 99m Tc-MDP) bone scanning, 67 Ga imaging, and 111 In-(or 99m Tc-hexamethylpropyleneam...

Prosthetic joint infections: radionuclide state-of-the-art imaging

“…In a preliminary study of seven patients undergoing revision surgery for hip (n05) or knee (n02) prostheses, Lorberboym et al reported for the first time on 99m Tc-recombinant annexin V scintigraphy [93]. They found four true-positive, two true-negative and one falsepositive annexin V images.…”

“…Note again, similarly to SPECT/CT, the presence of metal-induced CT artefacts. Performing a PET/CT study was, in this particular case, not contributive uptake in the periprosthetic region is more common and intense in infected prostheses than in aseptic loosening [93].…”

Technetium-99m-labeled annexin V imaging for detecting prosthetic joint infection in a rabbit model

“…Recently, Mordechai et al [13] reported that in a clinical trial 99m Tc-recombinant human annexin V imaging showed high sensitivity (100%) and low specificity (67%) for diagnosing PJI. The results of our present study improved on this specificity (83.3%).…”

“…It is widely used for in vivo detection of apoptotic cells in cardiovascular disease and cancer [11] . Other studies using various animal models and human beings have shown that 99m Tc-annexin V can also detect acute, subacute, and chronic infection [9] , [12-13] . In the present study, we investigated whether 99m Tc-annexin V imaging was effective in differentiating early stage PJI from uninfected prosthetic joints in a validated rabbit model [14] .…”

SPECT and PET radiopharmaceuticals for molecular imaging of apoptosis: from bench to clinic

“…In addition, as shown in Table 3, 99m Tc-Annexin V radiopharmaceuticals have also been used to image patients with diseases such as infection of prostheses, Crohn's disease, glaucoma [38–40]. Preliminary clinical data in these patients demonstrated the clinical use of 99m Tc-Annexin V as a diagnostic biomarker for monitoring apoptosis (Figure 2).…”