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Feasibility study for PET imaging of pulmonary fibrosis with cis-4-[F-18]fluoro-L-proline (FP).

Gupta-NC; Wallace-W; Mazza-S; Hubbs-A; Raylman-RR; Keane-M; Batelli-L
J Nucl Med 1998 May; 39(5)(Suppl S):116P-117P
Proline is a major amino acid in collagen synthesis. Its tissue incorporation can measure the rate of collagen synthesis in fibrosis. We prospectively studied the uptake and regional distribution of FP in the test and control rabbit models of induced silicosis with fibrosis. The cis-4-[F18]fluoro-L-proline was synthesized in a GE FDG Microlab by the [F18jfluoride displacement of tosylate from the trans isomer of N-t-BOC-0-p tosyloxy-L-proline methyl ester followed by hydrolytic deprotection. Twenty one rabbits, in batches of three rabbits each were imaged at 5 months postinstillation. We studied three rabbit models of silicosis (silica instilled), inflammatory control (titanium dioxide instilled) and instillation control (saline instilled). Dynamic emission imaging sequence (10 sec x 11, 20 sec x 5, 30 sec x 1, 60 sec x 1,5 min x 1, 10 min x 3, 20 min x 7) was performed up to 3 hrs postinjection of 1 mCi of FP. The degree and rate of radiotracer uptake in the lungs of test and control rabbits was compared to the histopathologic assessment of fibrosis. FP uptake in various lung zones, as scored by two observers blindly, was significantly higher in the test as compared to inflammatory (p<0.005) and saline controls (p<0.005). Fibrosis scores on trichrome staining were also higher in the silica group than titania (p<0.05) or saline group (p<0.005). FP uptake curve showed gradual upslope in abnormal lung regions in silicotic animals with slow plateau seen at 50-60 min. Lesion/background ratios in silicotic lungs ranged from 1.51 to 4.3 at two hours (mean+/-SD:2.49+/-l.15) and were higher than at 30, 60 or 90 min in silicotic group. UB ratio were 2.35+/-0.71 at one hour. Normal FP uptake was seen in liver and shoulder joints. Thus, preliminary FP imaging data in animal model demonstrates significant tracer uptake in the lung regions with induced fibrosis at 2 hrs. Further controlled studies should elucidate the role of FP as a marker of active and early pulmonary fibrosis.
Pulmonary-system-disorders; Pulmonary-disorders; Pulmonary-function; Pulmonary-congestion; Fibrous-bodies; Fibrogenicity; Fibrosis; Fibrogenesis
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Journal of Nuclear Medicine
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division