RIKEN Center for Life Science Technologies, 6-7-3 Minatojima Minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Department of Molecular and Cellular Biology, Kobe Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd, Kobe, Hyogo, Japan.
Mol Imaging Biol. 2017 Oct;19(5):746-753. doi: 10.1007/s11307-016-1039-5.
In vivo detection of pathological insults during the early stages of rheumatoid synovitis is essential to allow early anti-inflammatory treatment for prevention of joint destruction. Whether rheumatoid synovitis pathology and the efficacy of therapies can be visualized by positron emission tomography (PET) tracers specific to the inflammatory process was investigated.
Using a collagen-induced experimental rat model of rheumatoid arthritis, in vivo imaging using the PET tracers [C]PK11195, which binds to the translocator protein mainly expressed on myeloid cells, and [C]ketoprofen, for cyclooxygenase imaging, was performed. To evaluate therapeutic efficacy, model animals were administered the tumour necrosis factor alpha blocker etanercept subcutaneously.
[C]PK11195 and [C]ketoprofen uptakes were significantly higher in inflamed paws of collagen-induced arthritis rats than in normal rats. The data showed a correlation between tracer uptake values and paw swelling. After treatment with etanercept, [C]ketoprofen uptake was significantly lower in treated animals than in untreated ones, whereas [C]PK11195 uptake in the inflamed regions was comparable to that in the untreated group.
With [C]PK11195 and [C]ketoprofen tracers, non-invasive in vivo PET imaging for rheumatoid synovitis can provide diagnostic evidence of early synovitis and allow monitoring inflammatory cell activity during treatment.
在类风湿性关节炎早期炎症阶段检测病理性损伤对于早期抗炎治疗以预防关节破坏至关重要。探讨针对炎症过程的正电子发射断层扫描（PET）示踪剂是否可用于可视化类风湿性关节炎的病理变化和治疗效果。
使用胶原诱导的实验性大鼠类风湿关节炎模型，通过 PET 示踪剂[C]PK11195（主要与髓样细胞表达的转位蛋白结合）和[C]酮洛芬（用于环氧化酶成像）进行体内成像。为了评估治疗效果，模型动物接受了肿瘤坏死因子-α抑制剂依那西普皮下给药。
与正常大鼠相比，[C]PK11195 和 [C]酮洛芬在胶原诱导性关节炎大鼠的炎症性爪子中的摄取明显更高。数据显示示踪剂摄取值与爪子肿胀之间存在相关性。在用依那西普治疗后，治疗组动物的[C]酮洛芬摄取明显低于未治疗组，而炎症区域的[C]PK11195摄取与未治疗组相当。
使用 [C]PK11195 和 [C]酮洛芬示踪剂，类风湿性关节炎的非侵入性体内 PET 成像可以提供早期滑膜炎的诊断证据，并允许在治疗期间监测炎症细胞活性。
