Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tübingen, Germany.
J Nucl Med. 2013 Jan;54(1):151-8. doi: 10.2967/jnumed.112.106740. Epub 2012 Dec 4.
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'-(18)F-fluorothymidine ((18)F-FLT).
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 (18)F-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 (18)F-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.
Analysis of the different stages of arthritic joint disease revealed enhanced (18)F-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 (18)F-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 (18)F-FLT PET data. PET/CT and PET/MR imaging measurements enabled us to identify whether the (18)F-FLT uptake was located in the bone or the soft tissue.
Noninvasive in vivo measurement of cell proliferation in experimental arthritis using (18)F-FLT PET is a promising tool to investigate the extent of arthritic joint inflammation.
本研究旨在探讨使用 PET 增殖示踪剂 3'-去氧-3'-(18)F-氟代胸腺嘧啶核苷（(18)F-FLT），在不同阶段的实验性关节炎中，对体内细胞增殖进行非侵入性测量的可行性。
我们向小鼠注射含有葡萄糖-6-磷酸异构酶特异性抗体的血清以诱导实验性关节炎，并向对照小鼠注射对照血清。在疾病发作后 1、3、6 和 8 天，对注射 (18)F-FLT 的动物进行 PET、PET/CT 或 PET/MR 成像分析，然后进行放射自显影分析。通过在标准化感兴趣区域上绘制图像，从 PET 图像中定量测量踝关节和前脚掌的 (18)F-FLT 摄取量。为了将体内 PET 数据与细胞增殖相关联，我们在相应时间点对患病和健康关节进行 Ki-67 免疫组织化学分析。
对关节炎关节疾病的不同阶段进行分析显示，在关节炎踝关节（2.2 ± 0.2 %ID/g）和前脚掌（2.1 ± 0.3 %ID/g）中的 (18)F-FLT 摄取明显增强，与健康踝关节（1.4 ± 0.3 %ID/g）和前脚掌（1.5 ± 0.5 %ID/g）相比，在葡萄糖-6-磷酸异构酶血清注射后 1 天即可观察到明显的关节炎组织学迹象，但踝关节肿胀程度较轻。踝关节（3.5 ± 0.3 %ID/g）中的 (18)F-FLT 摄取水平在第 8 天达到最大。关节炎踝关节和前脚掌的 Ki-67 免疫组织化学染色与体内 (18)F-FLT PET 数据具有很强的相关性。PET/CT 和 PET/MR 成像测量使我们能够识别 (18)F-FLT 摄取是位于骨骼还是软组织中。
使用 (18)F-FLT PET 对实验性关节炎进行体内细胞增殖的非侵入性测量是一种很有前途的工具，可以用来研究关节炎关节炎症的程度。
