Chandrupatla Durga M S H, Weijers Karin, Gent Yoony Y J, de Greeuw Inge, Lammertsma Adriaan A, Jansen Gerrit, van der Laken Conny J, Molthoff Carla F M
Department of Rheumatology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, P.O. Box 7057, 1007 MB, 1081 HV Amsterdam, The Netherlands.
Biomed Res Int. 2015;2015:509295. doi: 10.1155/2015/509295. Epub 2015 Jan 28.
To widen the therapeutic window for PET guided evaluation of novel anti-RA agents, modifications were made in a rat model of rheumatoid arthritis (RA). Arthritis was induced in the right knee of Wistar rats with repeated boosting to prolong articular inflammation. The contralateral knee served as control. After immunization with methylated bovine serum albumin (mBSA) in complete Freund's adjuvant and custom Bordetella pertussis antigen, one or more intra-articular (i.a.) mBSA injections were given over time in the right knee. Serum anti-mBSA antibodies, DTH response, knee thickness, motion, and synovial macrophages were analyzed and [18F]FDG(-general inflammation) and (R)-[11C]PK11195 (macrophages-)PET was performed followed by ex vivo tissue distribution. Significant anti-mBSA levels, DTH, swelling of arthritic knee, and sustained and prolonged macrophage infiltration in synovial tissue were found, especially using multiple i.a. injections. Increased [18F]FDG and (R)-[11C]PK11195 accumulation was demonstrated in arthritic knees as compared to contralateral knees, which was confirmed in ex vivo tissue distribution studies. Boosting proved advantageous for achieving a chronic model without remission. The model will offer excellent opportunities for repeated PET studies to monitor progression of disease and efficacy of novel therapeutic agents for RA in the same animal.
为了拓宽正电子发射断层扫描（PET）引导下新型抗类风湿关节炎（RA）药物评估的治疗窗口，我们对类风湿关节炎大鼠模型进行了改良。通过反复加强免疫在Wistar大鼠右膝诱发关节炎，以延长关节炎症。对侧膝关节作为对照。在用完全弗氏佐剂和定制的百日咳博德特氏菌抗原中的甲基化牛血清白蛋白（mBSA）免疫后，随着时间的推移在右膝进行一次或多次关节内（i.a.）mBSA注射。分析血清抗mBSA抗体、迟发型超敏反应（DTH）、膝关节厚度、活动度和滑膜巨噬细胞，并进行[18F]氟代脱氧葡萄糖（-全身炎症）和（R）-[11C]PK11195（-巨噬细胞）PET检查，随后进行离体组织分布研究。发现了显著的抗mBSA水平、DTH、关节炎膝关节肿胀以及滑膜组织中持续且延长的巨噬细胞浸润，尤其是使用多次关节内注射时。与对侧膝关节相比，关节炎膝关节中[18F]FDG和（R）-[11C]PK11195的蓄积增加，这在离体组织分布研究中得到了证实。加强免疫被证明有利于建立无缓解的慢性模型。该模型将为在同一只动物中重复进行PET研究以监测疾病进展和新型RA治疗药物的疗效提供绝佳机会。
