Prosthetic joint infection
When a replacement hip or knee might be infected, doctors can label a small sample of the patient's own white blood cells with a radioactive tracer and watch, over a day, whether they gather around the implant the way they would around a real infection.
Overview
Distinguishing infection from aseptic loosening around a hip or knee prosthesis matters because the treatments diverge completely: infection needs antibiotics and usually staged revision surgery, while loosening needs a single revision. Radiolabelled white blood cell (WBC) scintigraphy, most often with Tc-99m-HMPAO-labelled autologous leukocytes, is the nuclear medicine reference standard for this question when a three-phase bone scan is positive or equivocal, because inflammatory cells are actively recruited to infected tissue but not to sites of sterile mechanical loosening.
The EANM procedural guideline specifies three imaging time points - roughly 30-60 minutes, 2-4 hours, and 20-24 hours after reinjection of the labelled cells - because the diagnostic sign is an increase in uptake over time, not simply the presence of uptake; a decrease or stable pattern between the delayed and late images points to a sterile process instead. Reported sensitivity for periprosthetic joint infection is around 86-93% and specificity 94-100% in pooled series, and pairing WBC scintigraphy with a bone marrow scan (Tc-99m sulfur colloid) further increases specificity, since discordant uptake - positive on WBC imaging, negative on marrow imaging - is highly suggestive of infection while concordant uptake in both usually reflects normal marrow expansion rather than infection.
The 2019 EANM/EBJIS/ESR multidisciplinary consensus places WBC scintigraphy (with or without a bone marrow scan) as the preferred nuclear imaging test after a positive three-phase bone scan, ahead of anti-granulocyte antibody imaging, and notes that antibiotic therapy should not be stopped purely to accommodate the scan, since the evidence that antibiotics blunt its accuracy is weak. FDG PET/CT is an alternative in some centres, but non-standardised uptake criteria around a metal prosthesis and physiological postoperative activity for months after surgery limit its specificity, and the 2024 EANM/SNMMI FDG infection guideline gives detailed protocol points for this specific use.
State of the art
- The EANM procedural guideline for white blood cell and anti-granulocyte scintigraphy (2018) and the 2019 EANM/EBJIS/ESR consensus document define current acquisition, interpretation and diagnostic-pathway standards for periprosthetic joint infection.
- The 2024/2025 EANM/SNMMI FDG hybrid PET guideline for infection and inflammation gives updated, indication-specific protocol points for periprosthetic joint infection imaging with FDG PET/CT, including field-of-view and interpretation caveats around metal implants.
- SPECT/CT is now recommended whenever planar WBC imaging is positive, since it better localises uptake to bone versus soft tissue and improves overall diagnostic accuracy.
Prosthetic joint infection complicates roughly 1-2% of primary hip and knee replacements and up to 4% of revisions, out of well over a million hip and knee arthroplasties performed annually in the United States alone; it is now the leading cause of knee revision surgery.
Tc-99m-HMPAO-labelled autologous white blood cell scintigraphy at three time points (early, delayed, late), read as positive when uptake increases over time; add a bone marrow scan for higher specificity.
FDG PET/CT, interpreted with awareness that absence of peri-prosthetic uptake has a high negative predictive value but focal peri-prosthetic uptake alone is nonspecific, especially soon after surgery.
Serum CRP/ESR, synovial fluid white cell count and differential, and culture, per the 2019 EANM/EBJIS/ESR consensus criteria that combine clinical, laboratory, imaging and histological findings rather than relying on any single test.
Subtypes & biomarkers
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Open problems and what is being done
WBC labelling is technically demanding, requires an on-site cell-processing lab, takes most of a working day, and is not available in every hospital, which pushes many centres toward less specific FDG PET/CT or serological/synovial-fluid-only pathways.
There is no universally agreed percentage-increase threshold between delayed and late images for calling a scan positive; visual assessment still dominates over quantitative cut-offs.
Recently implanted prostheses (within the first year) still cause false positives on most nuclear imaging modalities because of normal postoperative inflammatory change, narrowing the window in which any of these tests are reliable.
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