The Challenges of Quantitative Measurement of Lung Deposition Using 99mTc-DTPA from Delivery Systems with Very Different Delivery Times

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Abstract
In quantifying aerosol delivery, the drug is often mixed with a radiolabel such as 99mTc-DTPA whose deposition is used as a proxy for the drug. 99mTc-DTPA deposited in the lung is cleared by a combination of absorption into the pulmonary circulation and mucociliary clearance. If administration is not instantaneous, the image will not include that clearance during administration, a problem raised if comparing devices with different administration times. However, if rates of clearance are measured, it will be possible to “correct” the initial image for the clearance that occurred during administration and before counting. Five adult males inhaled a 5-mL solution containing 99mTc-DTPA from a breath enhanced jet nebulizer (LC Plus®) over the course of 10 min and a 1.25-mL solution from a vibrating membrane device (eFlow®), which was delivered in 2.5 min. Quality assurance was the radioactivity count balance (RCB) defined as the difference in the total radioactivity pre-nebulization less post, divided by pre, and expressed as a percentage. Attenuation calculations used a 57Co flood source (Macey and Marshall). The “correction” for the clearance of 99mTc-DTPA was 0.91 ± 0.04 (mean ± SD) for the LC Plus® and 0.96 ± 0.02 for the eFlow®. RCB was −0.6 ± 3.5% for the LC Plus® and −4.7 ± 6.4% for the eFlow®, implying acceptable accuracy. For the LC Plus®, lung deposition was 15.9(13.4, 18.4)% (mean and 95% CI) of the charge dose, and for the eFlow® it was 32.0(29.0, 35.0)%. This technique gave an acceptable level of accuracy for quantitative planar imaging and allowed the comparison of delivery from devices with very different rates of delivery.