Use of technetium-99m HMPAO scintigraphy for the detection of amiodarone lung toxicity in a rabbit model

Abstract

Amiodarone (AD) is a very effective anti-arrhythmic drug, but its use is often associated with serious pulmonary complications such as pneumonitis and interstitial pulmonary disease. The aim of this study was to investigate the relationship between the amount of amiodarone intake (and the related development of lung toxicity) and the lung uptake of technetium-99m labelled D,L-hexamethylpropylene amine oxime (HMPAO). Eighteen white female New Zealand rabbits were divided into three groups and fed AD by gavage at doses of 10 (group A), 50 (group B) or 150 (group C) mg/kg daily. ^99mTc-HMPAO scintigraphy was performed at baseline and after 1, 2, 3 and 4 weeks of drug intake. Anterior images of 1 min duration were acquired at 30 min after the injection of 37 MBq ^99mTc-HMPAO. Regions of interest (ROIs) were drawn on the lungs (L) and the upper limb (B) as the background. L/B ratios were calculated using the mean counts. In groups A and B histopathological evaluation of the lungs of all rabbits was performed at the end of the 4 weeks of AD intake, while in group C it was performed at 2 weeks because of increased mortality. At baseline, mean L/B ratios for groups A, B and C were 2.8±0.3, 2.8±0.3 and 2. 8±0.4, respectively. After 3 weeks of AD intake, L/B ratios increased to 4.1±0.6 and 4.8±0.6 in groups A and B, respectively. The L/B ratio was 3.6±0.2 after 1 week of AD intake in group C. The correlation coefficients between the lung uptake of ^99mTc-HMPAO and AD doses for groups A, B and C were r=0.51 (P=0.037), r=0.74 (P=0.0002) and r=0.96 (P=0.0001), respectively. Histopathological findings related to AD lung toxicity, such as interstitial pneumonitis and foamy alveolar macrophages, were observed more frequently in groups B and C than in group A. According to our findings, ^99mTc-HMPAO lung uptake is correlated with AD dose. ^99mTc-HMPAO lung imaging can demonstrate AD-induced lung injury.