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Infection & Inflammation ImagingIn-111 / ⁹⁹ᵐTc-HMPAO WBC · ¹⁸F-FDG

Labeled-WBC, FDG, and bone-marrow imaging for infection and fever of unknown origin

Evidence B#infection#inflammation#FDG#WBCUpdated 2026-07-27 · Physician-reviewed
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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).

  • 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

BSNMMI/EANM guidelines for labeled-leukocyte imaging, combined WBC/marrow interpretation, and FDG-PET/CT in infection/inflammation.
BEANM/SNMMI recommendations for FDG-PET/CT in fever of unknown origin and large-vessel vasculitis.
Cite this page. Nuclear Medicine Atlas. “Infection & Inflammation Imaging.” v1.76, 2026-10-25. Permalink: https://nuc.med/infection-inflammation/ Report an issue
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