PET imaging of pulmonary fibrosis - reply.
Wallace-WE; Hubbs-AF; Keane-MJ; Battelli-LA; Ma-J; Schleiff-P; Gupta-NC; Mazza-SM; Bishop-HA
J Nucl Med 2003 Mar; 44(3):484
The pilot study of 18F.fluoroproline (FP) imaging of silica instillation-induced pulmonary fibrosis in rabbits (1), supplemented with information in the above letter to the editor and our investigations ,(2), suggest that PET imaging using 18F-FP has the sensitivity to detect metabolic events involved in pulmonary response to some respirable quartz dust exposures. The studies used different isomers of FP, cis in ours (2) and mostly trans in the other, as reported in the letter, and images were read for different scanning intervals. These factors may be involved in the differences seen in response versus time after dust challenge. All emission data in our study were corrected for tissue attenuation, as reported (2), and planned analyses .of shorter scanning-time data acquired in our study may clarify the question, but the much stronger dust doses administered in our study (in which instillation was purposefully not directed to a particular lung or lobe as an added experimental blindfold) might be a significant factor. The range of conditions of exposure and response under which early or progressive stages of disease such as silicosis or asbestosis could be so detected or evaluated as metabolic events (e.g., exacerbated uptake or incorporation in collagen synthesis of the labeled proline analog) is to be determined. Questions of specificity persist: tritiated-proline autoradiography has been used for some time to study fibroblast synthesis of collagen (3), but little quantitative information exists on the fractional distribution of the label between alveolar cells involved in the inflammatory response (e.g. neutrophils) versus interstitial fibroblast incorporation of the labeled proline. 18F.FDG has been shown to be taken up specifically by inflammation-related neutrophil influx in response to microcrystalline silica challenge (4). Further, it might be important to use tritiated FP itself in addition to tritiated proline in such studies. A report on diastereomeric effects on 4-18P-FP metabolism and uptake in tumors in mice (5) indicated differences between uptake and incorporation for different FP isomers. The questions of the adequacy of the sensitivity and specificity of the method (e.g., for application in studies of occupational exposure and disease) appear to be amenable to investigation. If found to be accurate, the technique potentially would be highly useful diagnostically. However, as a cautionary note to clinical trials: We have seen evidence of eosinophilic endarteritis in some lung histopathology sections of our rabbits. We are investigating this finding to determine whether the vascular inflammation was endemic to the animals or was caused by FP or by nonradiolabeled contaminants in our test article, such as residue from protective groups on the precursor used in 18F-FP synthesis.
Pulmonary-system; Pulmonary-system-disorders; Fibrosis; Models; Silica-dusts; Silicates; Respirable-dust; Silicosis; Laboratory-animals; Animal-studies; Animals; Lung-fibrosis; Particulate-dust; Particulates
Naresh C. Gupta, MD, WVU PET Center, P.O. Box 9236, Health Sciences Center South, Morgantown, WV 26505
Journal of Nuclear Medicine