Radiopharmaceuticals in Bone Scans

Nuclear Medicine - Skeletal System

• Bone scans often provide earlier diagnoses and reveal more lesions compared to radiographic procedures.

Radiopharmaceuticals

• Technetium-labeled diphosphonates, especially methylene diphosphonate, are commonly used for skeletal imaging.
• Diphosphonates exhibit rapid renal excretion, achieving a high target-to-non-target ratio within 2-3 hours post-injection.
• 50% to 60% of the activity localizes in bone, with the remainder cleared by the kidneys.
• Maximal skeletal uptake usually occurs around 5 hours post-injection.
• The biological half-life is approximately 24 hours.

Important Points

• Avoid injecting air into the mixing vial during phosphate radiopharmaceutical preparation to prevent technetium oxidation, which impairs phosphate tagging.
• Administering the radiopharmaceutical more than 4 hours after preparation can lead to gastric and thyroid visualization on bone scans due to free pertechnetate.

Accumulation of Technetium in Bone

• Blood supply is the primary factor; a fourfold increase in blood flow increases bone uptake by 30% to 40%.
• Capillary permeability, local acid-base balance, fluid pressure within bone, hormones, vitamins, quantity of mineralized bone, and bone turnover also contribute to technetium accumulation.

Bone Scan Indications

• Infections: osteomyelitis, septic arthritis
• Metabolic bone disease
• Unexplained musculoskeletal pain.
• Pediatric: suspected non-accidental injury, tumors (primary or secondary)
• Detection and follow-up of metastatic disease.
• Differentiation between osteomyelitis and cellulitis.
• Determination of bone viability (infarction or avascular necrosis)
• Evaluation of fractures difficult to assess on radiographs, including stress fractures and complex fractures.
• Evaluation of prosthetic joints for infection or loosening.
• Biopsy site determination.

Technique

• Routine planar scans involve intravenous injection of 10-20 mCi (370-740 MBq) of technetium diphosphonate.
• Images are typically acquired 2-4 hours after injection.
• The injection site should be distant from suspected osseous pathologies.
• Slight extravasation of isotope at the injection site can lead to increased soft tissue activity.

Three-Phase/Four-Phase Study

• In patients suspected of osteomyelitis or cellulitis, a three-phase study is performed—radionuclide angiogram, initial blood pool image, and routine images at 2-3 hours.
• In rare cases, a four-phase study (additional images at 18-24 hours) is used for patients with renal failure who have poor soft tissue clearance.

MDP Circulation and Elimination

• Following IV injection, MDP circulates in the vascular system briefly and then equilibrates within the extravascular space.
• MDP accumulates rapidly in bone and is subsequently excreted through urine.
• Approximately half the administered dose is eliminated within 4 hours, leading to a high bone-to-background ratio.
• Exceptions may exist in cases of poor renal function.

Patient Preparation

• Maintain good hydration with oral fluids, especially after the injection and before scanning.
• Empty the bladder routinely to minimize radiation exposure to pelvic organs.
• Incontinence considerations and risks of contamination should be noted and addressed.

Patient Imaging

• Whole-body imaging is performed 2-4 hours post-injection using a moving table.
• This can use a dual-head gamma camera for simultaneous anterior-posterior views or a single-head setup for spot views.
• Oblique views of the sternum and ribs, lateral views of lower legs and pelvis, and magnification views are sometimes beneficial in certain cases (e.g., hands/wrists, pediatric hip).

Increased Vascularity and Permeability

• Increased vascularity and permeability contribute to the early accumulation of MDP in bone tumors, healing trauma, inflammatory, and infected bone conditions.

Bone Scan Summary

• Radiopharmaceutical: ^99mTc methylene diphosphonate (MDP).
• Activity administered: 600 MBq (15 mCi) to 800 MBq (20 mCi) (and adjusted for children)
• Effective dose equivalent: 3 mSv (300 mrem)
• Patient preparation: good hydration, empty bladder.
• Collimator: low-energy, high resolution
• Imaging: dual-head gamma camera—scan.

Normal Appearances and Interpretation

• In normal adults, individual bones are visualized and uptake is symmetric about the midline.
• There may be some background soft tissue uptake, particularly in obese patients.
• The kidneys and urinary bladder should be identifiable.

Adolescent Bone Scan

• Adolescent anterior/posterior images often show increased activity around epiphyseal plates, typically pronounced in knees, ankles, shoulders, and wrists.

Areas of Common Activity

• Focal maxillary or mandibular alveolar ridge (dental).
• Lower cervical spine (often due to spinal curve).
• Prominent sternum, sternoclavicular and acromioclavicular joints, and the shoulders, iliac crests, and hips.
• Knees (common in older patients exhibiting arthritic changes).
• Posterior view shows thoracic spine, scapulae, and sacroiliac joints.

Identifying Bone Abnormalities

• Asymmetric osseous activity is significant, requiring suspicion.
• Renal and bladder activity must be routinely assessed, specifically for focal space-occupying lesions.
• Scan timing and patient positioning can affect activity accumulation, and renal obstruction requires repeated scans with patient movement to distinguish obstruction.
• Sites of Injection, lymphatics and consequent abnormalities should be noted.

Metastatic Disease

• Multiple focal areas of intensely increased MDP uptake are characteristic, preferentially involving the axial skeleton.
• Metastatic activity reveals potential asymmetry during scans.
• Repeated scans with temporal evaluation of progression or regression can be helpful for evaluating patients and tumors.

Bone Scan Compared to Radiography

• For a lytic lesion to be visualized, significant demineralization (30-50%) is often required.
• Bone scans typically detect metastatic lesions earlier than radiographs.
• Radiographs have a higher false negative rate (50% in some tumor types), whereas bone scanning can have low false negative rates in common cancers.

Bone Scan for Cancer Patients

• Bone scans are often employed in patients experiencing bone pain, detecting metastases in approximately 80% of patients with known neoplasms exhibiting bone pain.
• Asymptomatic patients with suspected metastases potentially benefit from bone scintigraphy, but the applicability versus cost implications must be evaluated for those with particular tumor types (i.e. low rates of osseous metastases).

Follow-up Bone Scans

• Follow-up in advanced breast and prostate cancer patients needs caution.
• Early response to chemotherapy can lead to an increased uptake of bone that can mimic new lesions.
• Bone lesions appearing 6 months post-therapy usually indicate disease progression.

Malignant Bone Tumors - Osteosarcoma

• Historically, follow-up bone scans were often not helpful in osteosarcoma patients as pulmonary metastases frequently preceded osseous metastases.
• Aggressive chemotherapy has altered this natural history, and around 20% of patients show osseous metastases before lung metastases.

Malignant Bone Tumors - Ewing Sarcoma

• Ewing sarcoma is less common yet frequently occurs in the pelvis, ribs, or femur.
• Up to 11% of patients can present with osseous metastases.

Benign Osseous Neoplasms

• Most malignant lesions are initially hyperemic and accumulate more radiopharmaceutical.
• An early blood pool image can be helpful in identifying benign lesions, as such lesions will show little to no increased uptake.
• A significant exception is osteoid osteoma, which often exhibits intense activity.

Trauma

• Fractures potentially missed on regular radiographs may be detected using CT, MRI, or radionuclide bone scanning.
• MRI is preferable for single localized trauma, while bone scanning is effective in assessing multifocal suspected trauma.

Fractures - Bone Scan Appearance

• Acute fractures typically exhibit generalized, diffuse activity increases around the fracture site.
• Subacute fractures display more localized and intense activity over 2-3 months.
• Healing fractures exhibit a gradual decline in radiotracer activity intensity.

Pelvic and Spinal Fractures

• Pelvic and spinal fractures in the early phase initially display low activity in only 30% of scans (first 3 days)
• Recent axial and long bone fractures commonly appear by day 14
• Skull fractures don't typically exhibit activity.
• Rib fractures manifest as concentrated activity points, distinct from the linear activity of metastases (often consecutive); they exhibit increased activity and are readily recognized.

Occult Hip Fracture

• Occult hip fractures may require up to 3 days to be detectable in the elderly using bone scans.
• MRI is often preferred due to its speed.

Stress Fracture

• Plain radiographs may not detect stress fractures for 7-10 days potentially leading to delay in diagnosis and treatment.
• Radionuclide bone scan is often positive at clinical presentation and is a useful diagnostic tool.

Osteomyelitis

• Early bone involvement in inflammatory diseases is often challenging to detect using conventional radiography.
• MRI is effective, but limited by cost and use in patients with infected metal.
• Radioisotope scanning demonstrates elevated activity in soft tissue and underlying bony structures.

Radiopharmaceuticals - Osteomyelitis

• ^99mTc-diphosphonate, indium-111- (¹¹¹In-), ^99mTc-labeled leukocytes, ¹⁸F-FDG, and gallium-67 citrate are potential radiopharmaceuticals for diagnosing Osteomyelitis.
• For differentiation between osteomyelitis and cellulitis on ^99mTc-diphosphonate scans, a radionuclide angiogram and immediate blood pool images (within 2-3 hours) are needed.

Cellulitis vs Osteomyelitis

• Cellulitis shows increased blood flow (perfusion), diffuse elevated activity in soft tissue, and decrease activity over time.
• Conversely, osteomyelitis demonstrates focal increased activity in the blood pool and delayed images.

Septic Arthritis

• Bone scan activity is elevated across all phases; the spread of osteomyelitis is typically focal on one side of the joint (as opposed to septic arthritis, which has diffuse increases on both sides of the joint).

Metabolic Bone Disease - Osteoporosis

• Osteoporosis is defined by decreasing bone density leading to an increased risk of fracture, commonly affecting elderly women.
• Vertebral compression fractures are a defining characteristic.
• Osteoporotic collapses manifest as decreased height and intense linear MDP uptake across the vertebral body (H-sign).

Additional Fractures

• Fractures in the sacrum in osteoporotic patients are a common presentation.
• These often manifest as a vertical increased uptake across sacral ala, bridged by horizontal uptake, resulting in a characteristic "H" sign.
• Bone densitometry, rather than bone scanning, is the best method for assessing bone density.