What are the key radiotracers used for Pyrexia of Unknown Origin (PUO) and which one is the best and why?

Key Radiotracers for Pyrexia of Unknown Origin (PUO): Optimal Selection and Rationale

[18F]FDG PET/CT is the most effective radiotracer for evaluating pyrexia of unknown origin, with superior diagnostic yield (56%), high sensitivity (84%), and ability to guide management in over 50% of cases. 1

Primary Radiotracer Options for PUO

1. [18F]FDG PET/CT (First-line)

• Diagnostic performance: Sensitivity 84%, specificity 62%, diagnostic yield 56%, accuracy 76% 1
• Clinical impact: Changes management in approximately 53% of cases 1
• Strengths:
  • Excellent negative predictive value (80.9-100%) effectively rules out focal pathology 1
  • Can detect infections, inflammatory conditions, and malignancies simultaneously 2
  • Particularly valuable when conventional imaging is negative or inconclusive 3
  • Identifies common PUO causes including endocarditis (11%), splenic abscesses, systemic juvenile idiopathic arthritis (5%), and inflammatory bowel disease (5%) 1

2. [18F]NaF PET/CT (Second-line for bone pathology)

• Strengths: Highly sensitive for bone metastases and areas of increased bone turnover 3
• Limitations: Lower specificity due to tracer accumulation in degenerative and inflammatory bone diseases 3
• Best use: When bone pathology is specifically suspected as the cause of PUO

3. Tc-99m Bone Scan (Alternative for bone assessment)

• Role: Often used for initial detection of metastases and staging of patients with cancer 3
• Limitations: Less sensitive and specific than MRI for certain metastases 3

4. Tc-99m SPECT/CT (For specific anatomical regions)

• Utility: Precisely localizes abnormalities, particularly useful for multiple collapsed vertebrae of different ages 3
• Limitations: Lower sensitivity compared to MRI for certain locations and cancer types 3

Clinical Implementation Algorithm

1. Initial assessment:

   • Evaluate inflammatory markers (elevated markers favor FDG-PET/CT) 1
   • Review prior antibiotic therapy (may reduce FDG-PET/CT sensitivity) 1
   • Assess if conventional imaging has been negative or inconclusive

2. Timing considerations:

   • Perform [18F]FDG PET/CT within 3 days of initiating glucocorticoid therapy to avoid false negatives 1
   • Earlier implementation (≤7 days from admission) associated with shorter hospital stays and lower costs 4

3. Special populations:

   • ICU patients: Consider [18F]FDG PET/CT if other diagnostic tests have failed to establish etiology and transport risk is acceptable 3
   • Post-surgical patients: CT imaging of operative area should be considered first when fever occurs days after surgery 3

Why [18F]FDG PET/CT is Superior for PUO

1. Comprehensive evaluation: Simultaneously assesses for infections, inflammatory conditions, and malignancies - the three most common causes of PUO 2, 5

2. Cost-effectiveness: Earlier use associated with shorter hospital stays and lower total costs 4

3. Management impact: High negative predictive value allows clinicians to confidently rule out serious pathology, leading to discharge decisions in 70% of negative scan cases 4

4. Diagnostic yield: Identifies the cause of fever in approximately 60% of cases, with accuracy of 90.5%, sensitivity of 93.8%, and specificity of 80% 2

Potential Pitfalls and Limitations

• False positives: Recent surgical procedures, foreign body reactions, inadequate myocardial FDG uptake suppression 1
• False negatives: Prior extended antibiotic therapy, small/mobile lesions, systemic diseases without focal manifestations 1
• Timing issues: Reduced sensitivity if performed after extended antibiotic therapy 1
• Preparation: Consider myocardial suppression preparation when cardiac etiology is suspected 1

Emerging Technologies

• PET/MRI: Shows potential but currently has insufficient data to support routine use in PUO evaluation 1
• [18F]FES (Fluoroestradiol): While approved for breast cancer evaluation, not yet established for PUO 3

For optimal diagnostic yield in PUO cases, [18F]FDG PET/CT should be considered early in the diagnostic pathway, particularly when conventional imaging and initial investigations have failed to identify the cause of fever.