Radionuclides in Orthopaedics

1. Basic Principles

• Radionuclides are radioactive isotopes that undergo spontaneous decay emitting gamma rays (from the nucleus) or X-rays (from electron orbital transitions).
• Images reflect metabolic function, not anatomy; spatial resolution is lower than CT/MRI.
• SPECT (Single Photon Emission Computed Tomography): the gamma camera rotates around the patient to generate 3D tomographic images, improving contrast resolution by eliminating overlapping activity.
• PET (Positron Emission Tomography): detects annihilation photon pairs, giving better spatial resolution than SPECT. Hybrid systems (SPECT/CT, PET/CT, PET/MRI) correlate functional with anatomic data.
• Rockwood and Green's Fractures in Adults, 10th Ed., p. 253

2. Radionuclides Used in Orthopaedics

• Miller's Review of Orthopaedics, 9th Ed., p. Nuclear Medicine table
• Rockwood and Green's Fractures in Adults, 10th Ed., p. 253
• Campbell's Operative Orthopaedics, 15th Ed. 2026

3. Skeletal Scintigraphy (Bone Scan)

Three-Phase Bone Scan

• Adding the three phases increases specificity from 74% to 94% for osteomyelitis.
• A four-phase study is sometimes used (24-hour delayed images) for complex infection scenarios.

Scan Appearances

• "Hot" lesion (increased uptake): increased osteoblastic + osteoclastic activity + regional hyperemia - seen in infection, fracture, tumour, degenerative joint disease.
• "Cold" lesion (decreased uptake): permeative/small round cell tumours, avascular necrosis (early), sequestrum, regions shielded by periosteal pus/vasospasm.

Overall Performance

• Highly sensitive, poor specificity - a normal scan largely rules out skeletal pathology; a positive scan requires further workup.

4. Gallium-67 Imaging

1. Increased regional blood flow and vascular permeability allow greater accumulation.
2. Neutrophils release lactoferrin during inflammation; gallium has a higher binding affinity for lactoferrin than transferrin.

• Imaging performed at 24-48 hours (or longer); relatively poor imaging agent because photon energies are not optimal for modern gamma cameras.
• Less dependent on vascular flow than technetium - can identify foci missed by bone scan.
• Cannot differentiate cellulitis from osteomyelitis.
• Difficulty distinguishing pyogenic from granulomatous infections.

• Best used in combination with ⁹⁹mTc bone scan for detection of osteomyelitis (especially spondylodiscitis): sensitivity 90%, specificity 100%, accuracy 94% with combined scanning.
• Useful for documenting resolution of infection (changes rapidly as active infection resolves).
• Localises in neoplasia - useful adjunct in tumour workup.

5. White Blood Cell (Leucocyte) Scintigraphy

Labeling Methods

• 50 mL blood drawn; leukocytes separated; incubated with ¹¹¹In-oxine (lipid-soluble, crosses cell membrane) for 30 min; reinjected.
• Imaging at 24 hours to allow leukocyte localisation and blood pool clearance.
• Preferred for chronic osteomyelitis and axial skeleton infections.

• 50-75 mL blood; labelled in plasma (no cell separation needed); faster preparation.
• Imaging at 4 hours for peripheral skeleton.
• Sensitivity 97.7%, specificity 96.8% for acute osteomyelitis.
• Preferred in children (smaller spleen radiation dose, less blood needed).
• Superior to bone scan in children under 6 months (poor bone scan sensitivity at that age).

Interpretation - Marrow Subtraction Protocol

• Sulfur colloid particles (0.1-2 µm) are taken up by reticuloendothelial cells in marrow, mapping normal marrow.
• In osteomyelitis: photopenic defect on sulfur colloid (marrow replaced) + increased activity on WBC scan = discordance = positive for infection.
• Congruent activity on both = normal marrow = no infection.

Limitations

• Labour-intensive; costly; requires processing of potentially infectious blood products.
• Diagnostic accuracy reduced in the axial skeleton.
• False-positives with periarticular nonunions/posttraumatic arthropathy.

6. In Vivo Labeling - Antigranulocyte Scintigraphy

• Uses monoclonal antibodies/fragments against granulocytes - no blood processing required.
• Distinguishes true infection (high granulocyte concentration) from areas of high metabolic activity without inflammation.
• Meta-analysis: sensitivity 81%, specificity 77% for osteomyelitis.

7. PET / FDG-PET

• Chronic osteomyelitis (especially axial skeleton): highest diagnostic accuracy of any nuclear technique.
• Bone and soft tissue tumours: delineates lesions and inflammatory activity at very early stages.
• PET/CT and PET/MRI provide simultaneous functional + anatomic correlation.

8. Marrow Imaging

• Taken up by reticuloendothelial cells in liver (85%), spleen (10%), marrow (5%).
• Half-life in blood: 2-3 minutes; imaging after 20-minute delay.
• Primary role: combined with ¹¹¹In WBC scan for osteomyelitis diagnosis (marrow subtraction technique, above).

9. Bone Density Measurement (Photon Absorptiometry)

10. Clinical Applications in Orthopaedics

Fractures

• Bone scans positive in 80% of fractures at 24 hours, 95% at 72 hours.
• Detects stress fractures and insufficiency fractures not visible on plain X-ray.
• Classic "Honda sign" (H-pattern uptake) in sacral insufficiency fractures.
• Useful in non-accidental trauma (child abuse): skeletal survey + bone scan together detect more injuries than either alone.
• Hyperemia (phases 1+2) normalises 4-8 weeks post-injury, helping age fractures.

Osteomyelitis / Infection

• Three-phase bone scan: good screening tool; if all three phases negative, infection essentially excluded.
• Combined ⁹⁹mTc + ⁶⁷Ga: sensitivity 90%, specificity 100%, accuracy 94% for spinal infection.
• WBC scintigraphy: gold standard for peripheral bone infection.
• FDG-PET: best for chronic/axial osteomyelitis.
• SPECT-CT with delayed bone scan increases sensitivity by localising areas of increased metabolism.

Avascular Necrosis (AVN)

• Early AVN: decreased uptake ("cold") due to vascular compromise.
• Reparative phase: increased uptake as revascularisation and new bone formation occur.
• Bone scan predates MRI as an early-detection tool, though MRI is now preferred.

Prosthetic Joint / Periprosthetic Infection

• Three-phase bone scan: increased specificity (74% → 94%) with three-phase technique.
• Normal bone scan essentially excludes loosening/infection.
• ¹⁸F-FDG PET/CT and ¹⁸F-NaF PET/CT used for periprosthetic joint infection (PJI) diagnosis.
• Gallium scan combined with bone scan: distinguishes aseptic loosening from infection.
• ¹¹¹In WBC scan: differentiates true infection from hematoma/seroma when MRI is equivocal.

Tumours / Neoplasia

• Whole-body bone scan: detection of skeletal metastases and primary bone tumours.
• "Cold" lesions in permeative tumours (small round cell tumours) that elicit little bone reaction.
• ⁶⁷Ga scan: localises inflammation and tumour; used in bone tumour workup.
• FDG-PET: best for staging and monitoring treatment response in bone malignancies.
• ¹⁸F-NaF PET: superior to ⁹⁹mTc bone scan for osteoblastic metastases.

Spinal Infection (Spondylodiscitis)

• ⁹⁹mTc bone scan: increased activity, diffuse on blood pool, focally increased on delayed views - persists for months.
• ⁶⁷Ga scan: particularly useful for soft tissue component of spondylodiscitis; changes rapidly with resolution.
• ¹¹¹In WBC scan: useful for abscess detection but less reliable in acute infections; false-negatives in chronic infection.

Reflex Sympathetic Dystrophy (CRPS)

• Three-phase ⁹⁹mTc bone scan: periarticular uptake pattern is characteristic; helpful in diagnosis.

11. Artifacts from Orthopaedic Hardware

12. Summary Comparison

• Rockwood and Green's Fractures in Adults, 10th Ed. 2025 - Nuclear Imaging, Bone Scintigraphy, Leucocyte Scintigraphy, PET sections (pp. 253-255, 963-964)
• Campbell's Operative Orthopaedics, 15th Ed. 2026 - Radionuclide Scanning, Nuclear Imaging for PJI
• Miller's Review of Orthopaedics, 9th Ed. - Nuclear Medicine table