Radiopharmaceuticals for Lung

Radiopharmaceuticals for lung imaging include:

  1. Lung perfusion agents – radiolabeled particles that are temporarily trapped in the lung’s arterioles and capillaries after iv injection and provide diagnostic information about regional blood flow to the lung.
  2. Lung ventilation agents – radioactive gases or radioaerosols that, after inhalation, demonstrate patency of the airways and alveolar system.

Physiology

  1. Perfusion - The pulmonary artery divides into 22 – 26 branches. At ~ 24 th branch, a connector artery (125 ± 15 μm) divides to form 2 distribution arteries (80 ± 20 μm). These divide into precapillary beds (25 ± 10 μm) that divide into capillary segments (8.2 ± 1.5 μm).
  2. Ventilation – Airways of the lung are divided into the conducting (bronchi and bronchioles), intermediate or transition (alveoli) and respiratory (alveoli and capillaries) functional zones. In the respiratory zone air and blood come into close contact to facilitate the exchange of oxygen and carbon dioxide.

Perfusion Imaging Agents
Tc-99m Macroaggregated Albumin (Tc-99m albumin aggregated or Tc-99m MAA)

  1. Compounding – A sterile aqueous suspension of Tc-99m labeled to human albumin aggregate particles at pH 3.8 – 8.0. Kits consist of a sterile lyophilized powder of nonradioactive ingredients (stannous chloride dihydrare , human albumin) sealed under nitrogen.
  2. Nonradioactive MAA kits are prepared by mixing sterile solutions of human serum albumin and stannous chloride in acetate buffer at a pH ~ 5. The solution is heated and mixed to form the aggregated particles and sieved to exclude particles larger than 10 – 90 μm. The suspension is divided, lyophilized and stored under nitrogen. Kits contain about 5 million particles
  3. The kit is prepared by aseptically adding the required amount of Tc-99m sodium pertechnetate to reconstitute and disperse the particles. The kit is allowed to stand at RT for up to 15 m to ensure maximum labeling.

Physical properties:

  1. Particle size:   13.5 ± 1.5 μm particles are ideal but impractical to prepare. Commercial kits contain particles 10 – 90 μm, with most between 20 – 60 μm.
  2. Particle number: The minimum number of particles for a satisfactory lung scan is 60,000.
  3. Particle hardness and composition: Particles should be biodegradable. Hardness is related to the temperature at which the particles are prepared.

Clinical use
Perfusion lung san (3 mCi), differential lung perfusion prior to lung Ca surgery, Right-to-left shunt evaluation

Localization
Biodistribution

  1. Capillary entrapment.
    After iv injection, >90% are extracted by the pulmonary bed on first pass through the lung.
  2. Particle distribution is related to regional blood flow. Clearance from lung results from particle fragmentation caused by blood cell bombardment and continuous forward and backward movement within arterioles until aggregates are small enough to traverse the capillary lumen.
  3. Particles 10 –70 μm in size clear lung with a biologic half-life of 4- 6 h. Following lung clearance, particles are phagocytized by the RES, primarily the liver.
Toxicity
  1. Pulmonary hypertension. Patient dose should not exceed 250,000 particles. Patients with known hypertension should no t receive more than 60,000 particles. Pediatric doses should not contain more than 50,000 particles in the newborn and 165,000 particles in children up to 1 year old.
  2. Methods are available to prepare low particle doses. With a reduction in available stannous ion, free pertechnetate may be present. As little as 5 – 10% free pertechnetate will be evident as thyroid uptake on lung scan.

Ventilation Imaging Agents

Xe-133

  1. Compliance
  2. Airway disease
    1. COPD
  3. Initial Breath, equalibrium, and washout

Tc-99m DPTA Radioaerosol

Localization
Biodistribution

  1. A droplet size smaller than 2 μm is necessary for good distribution and minimal large airway deposition.
  2. Typically, 30 – 50 mCi of Tc-99m DTPA in 4 mL is placed in a nebulizer.
    1. Aeosol droplets are generated by forcing air or oxygen through the nebulizer at 8 – 10 L/m at 25 – 50 psi.
    2. The greater the L/m the better the particle production
    3. The patient inhales the radioaerosol during normal breathing through a mouth with the nose clamped shut.
    4. Radioaerosol not used is trapped in a particle-retentive filter. Studies require 5 – 10 minutes of breathing. Typically, the patient receives 0.1 mCi/m of breathing.
    5. The clearance rate across the pulmonary epithelium int the blood is 1.5%/m (compared to 5.1%/m for Tc-99m pertechnetate).

Clinical use – The diagnosis of pulmonary embolism

  1. Comparision of ventilation and prefusion images
  2. Matched defect is COPD
  3. Mismatched defect is PE

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