Department of Radiology, Pediatric Radiology, Lucile Packard Children's Hospital, Stanford University, Stanford, California.
Department of Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany.
Clin Cancer Res. 2018 Dec 15;24(24):6223-6229. doi: 10.1158/1078-0432.CCR-18-1687. Epub 2018 Sep 17.
Osteonecrosis is a devastating complication of high-dose corticosteroid therapy in patients with cancer. Core decompression for prevention of bone collapse has been recently combined with the delivery of autologous concentrated bone marrow aspirates. The purpose of our study was to develop an imaging test for the detection of transplanted bone marrow cells in osteonecrosis lesions.
In a prospective proof-of-concept clinical trial (NCT02893293), we performed serial MRI studies of nine hip joints of 7 patients with osteonecrosis before and after core decompression. Twenty-four to 48 hours prior to the surgery, we injected ferumoxytol nanoparticles intravenously to label cells in normal bone marrow with iron oxides. During the surgery, iron-labeled bone marrow cells were aspirated from the iliac crest, concentrated, and then injected into the decompression track. Following surgery, patients received follow-up MRI up to 6 months after bone marrow cell transplantation.
Iron-labeled cells could be detected in the access canal by a dark (negative) signal on T2-weighted MR images. T2* relaxation times of iron-labeled cell transplants were significantly lower compared with unlabeled cell transplants of control patients who were not injected with ferumoxytol ( = 0.02). Clinical outcomes of patients who received ferumoxytol-labeled or unlabeled cell transplants were not significantly different ( = 1), suggesting that the added ferumoxytol administration did not negatively affect bone repair.
This immediately clinically applicable imaging test could become a powerful new tool to monitor the effect of therapeutic cells on bone repair outcomes after corticosteroid-induced osteonecrosis.
骨坏死是癌症患者接受大剂量皮质类固醇治疗的一种破坏性并发症。最近,对预防骨塌陷的核心减压术进行了改进,将自体浓缩骨髓抽吸物联合应用于该术式。我们研究的目的是开发一种用于检测骨坏死病变中移植骨髓细胞的影像学检测方法。
在一项前瞻性概念验证临床试验(NCT02893293)中,我们对 7 例骨坏死患者的 9 个髋关节进行了核心减压术前后的连续 MRI 研究。在手术前 24 至 48 小时,我们通过静脉注射超顺磁氧化铁纳米颗粒将细胞标记为铁氧化物,对正常骨髓中的细胞进行标记。手术过程中,从髂嵴抽吸并浓缩铁标记的骨髓细胞,然后将其注入减压通道。手术后,患者在骨髓细胞移植后 6 个月内接受了后续 MRI 检查。
在 T2 加权 MR 图像上,铁标记细胞可在进入通道中显示为暗(负)信号。与未接受 ferumoxytol 注射的对照患者( = 0.02)的未标记细胞移植相比,铁标记细胞移植的 T2*弛豫时间明显更低。接受 ferumoxytol 标记或未标记细胞移植的患者的临床结局无显著差异( = 1),这表明添加的 ferumoxytol 给药并未对骨修复产生负面影响。
这种即刻可临床应用的影像学检测方法可能成为监测皮质类固醇诱导的骨坏死治疗细胞对骨修复结果影响的有力新工具。