PT - JOURNAL ARTICLE AU - Kerstin Fuchs AU - Ursula Kohlhofer AU - Leticia Quintanilla-Martinez AU - Denis Lamparter AU - Ina Kötter AU - Gerald Reischl AU - Martin Röcken AU - Bernd J. Pichler AU - Manfred Kneilling TI - In Vivo Imaging of Cell Proliferation Enables the Detection of the Extent of Experimental Rheumatoid Arthritis by 3′-Deoxy-3′-<sup>18</sup>F-Fluorothymidine and Small-Animal PET AID - 10.2967/jnumed.112.106740 DP - 2013 Jan 01 TA - Journal of Nuclear Medicine PG - 151--158 VI - 54 IP - 1 4099 - http://jnm.snmjournals.org/content/54/1/151.short 4100 - http://jnm.snmjournals.org/content/54/1/151.full SO - J Nucl Med2013 Jan 01; 54 AB - The aim of this work was to study the feasibility of measuring cell proliferation noninvasively in vivo during different stages of experimental arthritis using the PET proliferation tracer 3′-deoxy-3′-18F-fluorothymidine (18F-FLT). Methods: We injected mice with serum containing glucose-6-phosphate-isomerase–specific antibodies to induce experimental arthritis, and we injected control mice with control serum. Animals injected with 18F-FLT 1, 3, 6, and 8 d after the onset of disease were analyzed in vivo by PET, PET/CT, or PET/MR imaging followed by autoradiography analysis. The 18F-FLT uptake in the ankles and forepaws was quantified on the basis of the PET images by drawing standardized regions of interest. To correlate the in vivo PET data with cell proliferation, we performed Ki-67 immunohistochemistry of diseased and healthy joints at the corresponding time points. Results: Analysis of the different stages of arthritic joint disease revealed enhanced 18F-FLT uptake in arthritic ankles (2.2 ± 0.2 percentage injected dose per gram [%ID/g]) and forepaws (2.1 ± 0.3 %ID/g), compared with healthy ankles (1.4 ± 0.3 %ID/g) and forepaws (1.5 ± 0.5 %ID/g), as early as 1 d after the glucose-6-phosphate-isomerase serum injection, a time point characterized by clear histologic signs of arthritis but only slight ankle swelling. The 18F-FLT uptake in the ankles (3.5 ± 0.3 %ID/g) reached the maximum observed level at day 8. Ki-67 immunohistochemical staining of the arthritic ankles and forepaws revealed a strong correlation with the in vivo 18F-FLT PET data. PET/CT and PET/MR imaging measurements enabled us to identify whether the 18F-FLT uptake was located in the bone or the soft tissue. Conclusion: Noninvasive in vivo measurement of cell proliferation in experimental arthritis using 18F-FLT PET is a promising tool to investigate the extent of arthritic joint inflammation.