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

Abstract

In quantifying aerosol delivery, the drug is often mixed with a radiolabel such as (99m)Tc-DTPA whose deposition is used as a proxy for the drug. (99m)Tc-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 (99m)Tc-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 (57)Co flood source (Macey and Marshall). The "correction" for the clearance of (99m)Tc-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.

Respiratory System Deposition with a Novel Aerosol Delivery System in Spontaneously Breathing Healthy Adults

“…11 Confirmation of accuracy for the in vitro data for adults would validate both the performance of this novel delivery system and the in vitro methodology used in the estimates of respiratory system deposition. It is recognized that, ideally, children with acute asthma should be part of the study, but this was considered not acceptable, for ethical reasons.…”

“…Counting was done as soon as practically possible after the end of nebulization, usually within 5-8 min, and then 5, 10, 15, and 20 min later. Details of this technique have been described previously, 11 with the exception that it was impossible to compare the amount of radioactivity pre-nebulization to postnebulization, since the absence of an expiratory filter prevented capturing all the aerosol as a measure of quality control.…”

“…Details of the selection of the regions of interest for the stomach, lungs, and mediastinum have been well described recently in healthy subjects. 11 All counts were corrected for radioactive decay, based on a half-life of 6 hours, starting at the time of imaging of the charged nebulizer pre-nebulization.…”

“…The natural logarithm of counts per pixel for the lung regions of interest was plotted against the time of acquisition from the first to the 5th acquisition, occurring 20 min later. 11 It is assumed that the radiolabel is deposited at a constant rate 15 and that its clearance is on a time-dependent exponential curve. A linear regression was done using the natural logarithm counts versus time, and the inverse of the slope is the time constant () of the lung clearance.…”

“…The inverse of this fraction multiplied by the total counts in the first image represented the total pulmonary deposition. Greater details of these calculations have been published recently in both healthy adults 11,16,17 and children and adults with lung disease. 18 If MgSO 4 had been used instead of saline, the total amount of counts in the nebulizer prior to nebulization would represent 600 mg of MgSO 4 in 6 mL of a 100 mg/mL solution.…”