Infection & Inflammation ImagingIn-111 / ⁹⁹ᵐTc-HMPAO WBC · ¹⁸F-FDG
Labeled-WBC, FDG, and bone-marrow imaging for infection and fever of unknown origin
Quick Answer
Two main strategies image infection. Labeled-WBC scintigraphy (In-111-oxine or Tc-99m-HMPAO leukocytes) is specific for neutrophilic infection (abscess, prosthetic-joint infection, diabetic foot) and is often paired with bone-marrow (sulfur-colloid) imaging to distinguish infection from marrow. FDG-PET/CT is highly sensitive across a broad range of infection and inflammation and excels in fever of unknown origin (FUO), large-vessel vasculitis, spinal infection, and vascular-graft/device infection. The single highest-yield concept is the WBC + marrow incongruence rule.
Definition & Scope
Infection/inflammation imaging localizes and characterizes infective and inflammatory foci that anatomic imaging cannot resolve or that require whole-body survey. The two pillars are cellular targeting (labeled leukocytes) and metabolic targeting (FDG uptake by activated inflammatory cells).
The Two Strategies
| Strategy | Targets | Strengths | Limits |
|---|---|---|---|
| Labeled WBC (± marrow) | Neutrophil migration | Specific for pyogenic infection; periprosthetic/bone | Labor-intensive; blood handling; less sensitive for low-grade/lymphocytic |
| FDG-PET/CT | Activated inflammatory-cell glucose | Whole-body, fast, very sensitive; FUO/vasculitis/spine/graft | Lower specificity (physiologic/post-op uptake) |
When to Use Which
| Question | Preferred |
|---|---|
| Prosthetic-joint infection; osteomyelitis in complex/violated bone | Labeled WBC ± marrow imaging |
| Fever of unknown origin | FDG-PET/CT (whole-body survey) |
| Large-vessel vasculitis (GCA/Takayasu) | FDG-PET/CT |
| Vascular graft / CIED / device infection | FDG-PET/CT (± WBC) |
| Spondylodiscitis | FDG-PET/CT (MRI complementary) |
| Diabetic-foot osteomyelitis (vs neuropathic/Charcot) | Labeled WBC ± marrow (MRI first-line anatomically) |
Labeled WBC + Marrow Imaging — the Core Concept
Leukocytes accumulate at sites of neutrophil-mediated infection. But normal and reactive marrow also takes up labeled WBCs, so the interpretation hinges on a paired Tc-99m-sulfur-colloid marrow scan:
- Congruent WBC + marrow uptake (same distribution) → marrow, not infection.
- Spatially incongruent uptake — WBC-positive, marrow-negative → infection.
This dual-tracer maneuver is what makes periprosthetic and complex osteomyelitis reads reliable, where marrow reconversion/displacement otherwise mimics infection.
FDG-PET/CT Applications
FDG accumulates in activated neutrophils, macrophages, and lymphocytes. High sensitivity plus whole-body coverage make it powerful for:
- Fever of unknown origin: a single survey often localizes an occult focus or an alternative diagnosis (malignancy, vasculitis).
- Large-vessel vasculitis: smooth, circumferential arterial-wall uptake (GCA/Takayasu); image before/early in steroid therapy (steroids suppress uptake).
- Spondylodiscitis and vascular-graft/prosthesis and CIED/device infection (with attention to post-implant physiologic uptake windows).
- Sarcoidosis activity and (with dietary prep) cardiac sarcoid.
Radiopharmaceutical Uptake Mechanisms
Labeled WBCs migrate to chemotactic infection foci (neutrophil-dependent — hence weaker for chronic/lymphocytic or vertebral infection). Tc-99m-HMPAO WBCs give better image quality and lower dose than In-111, but have urinary/biliary/bowel excretion complicating the abdomen (In-111 has none). FDG reflects glucose metabolism of activated inflammatory cells. Ga-67 (legacy) binds transferrin/lactoferrin.
Tracer Comparison
| Agent | Best roles | Notes |
|---|---|---|
| ⁹⁹ᵐTc-HMPAO WBC | Peripheral bone/soft-tissue, diabetic foot | Better images/lower dose; GU/bowel excretion |
| In-111-oxine WBC | Abdomen (no bowel/GU excretion), delayed imaging | Lower resolution; 24 h imaging |
| ¹⁸F-FDG | FUO, vasculitis, spine, graft/device | Sensitive, whole-body; lower specificity |
| ⁶⁷Ga citrate | Spinal osteomyelitis, sarcoid (legacy) | Delayed imaging; largely superseded |
Reporting Checklist
- For periprosthetic/bone questions, always interpret WBC against the marrow scan (congruent = marrow; incongruent = infection).
- State timing relative to surgery/instrumentation/steroids (all confound uptake).
- For vasculitis, describe distribution and grade wall uptake; note steroid status.
- Address physiologic bowel/muscle/brown-fat FDG and WBC excretion patterns.
Common Pitfalls
- Reading WBC uptake without marrow imaging in periprosthetic questions — marrow mimics infection.
- Post-surgical/inflammatory FDG uptake mistaken for infection (respect timing windows).
- Steroids suppressing vasculitis uptake — image before/early.
- Physiologic bowel, muscle, brown-fat FDG confounding FUO reads; HMPAO-WBC GU/bowel excretion in the abdomen.
Board Pearls
The single highest-yield concept: because marrow also takes up labeled leukocytes, pair the WBC scan with a sulfur-colloid marrow scan — congruent WBC + marrow uptake = marrow (no infection); spatially incongruent (WBC-positive, marrow-negative) = infection. This is the crux of prosthetic-joint and complex-osteomyelitis reads.
Labeled WBC (± marrow) is specific for neutrophilic infection (prosthetic joint, diabetic foot, complex osteomyelitis); FDG-PET/CT is the whole-body workhorse for FUO, large-vessel vasculitis, spinal infection, and graft/device infection — more sensitive, faster, higher-resolution.
Practical cautions: post-surgical/instrumentation inflammation causes FDG false positives (timing matters), and steroids suppress vasculitis uptake (image before/early). Tc-99m-HMPAO WBC gives better images and lower dose than In-111 but has urinary/biliary/bowel excretion to account for in the abdomen (In-111 has none). Ga-67 persists as a legacy fallback (spinal osteomyelitis, sarcoid activity).
Related Pages
- Tracer: Gallium-67 (legacy roles); FDG.
- Related: Cardiac sarcoidosis (suppression-prep FDG); pitfalls: Pearls, pitfalls & normal variants.
Figure / Diagram Suggestions
- The WBC + marrow congruence/incongruence decision plate (periprosthetic infection).
- A strategy selector flow (labeled WBC vs FDG by clinical question).
- Large-vessel vasculitis FDG pattern (circumferential wall uptake) with the steroid caveat.
Self-Check (Board-Style)
Q1. A periprosthetic hip shows increased labeled-WBC uptake. What second study is needed and how does it decide infection?
Answer: A Tc-99m-sulfur-colloid marrow scan. Congruent WBC + marrow uptake = marrow (no infection); incongruent (WBC-positive, marrow-negative) = infection.
Q2. Which modality is first-line for fever of unknown origin and large-vessel vasculitis, and what timing caveat applies to vasculitis?
Answer: FDG-PET/CT. For vasculitis, image before or early in steroid therapy — corticosteroids suppress vascular-wall FDG uptake.
Q3. Why choose In-111 over Tc-99m-HMPAO labeled WBC for a suspected abdominal abscess?
Answer: In-111-oxine WBC has no bowel/urinary excretion, avoiding the physiologic abdominal activity that HMPAO-WBC shows — cleaner for abdominal infection (and it allows 24-h delayed imaging).
Q4. Why can labeled-WBC imaging under-perform for vertebral osteomyelitis?
Answer: Vertebral/chronic infection is often not strongly neutrophil-mediated and can appear photopenic; FDG-PET/CT (with MRI) is preferred for spondylodiscitis.
Evidence & sources
https://nuc.med/infection-inflammation/ Report an issue