White Sarah B, Kim Dong-Hyun, Guo Yang, Li Weiguo, Yang Yihe, Chen Jeane, Gogineni Venkateswara R, Larson Andrew C
From the Department of Radiology, Division of Vascular and Interventional Radiology, Medical College of Wisconsin, Milwaukee, Wis (S.B.W., V.R.G.); Department of Radiology (S.B.W., D.H.K., Y.G., W.L., Y.Y., J.C., A.C.L.) and Robert H. Lurie Comprehensive Cancer Center (D.H.K., A.C.L.), Northwestern University, 710 N Fairbanks Ct, Olson 8th floor 8-317, Chicago, IL 60611; Department of Chemical and Biological Engineering (J.C.) and Department of Biomedical Engineering (A.C.L.), Northwestern University, Evanston, Ill.
Radiology. 2017 Dec;285(3):809-819. doi: 10.1148/radiol.2017161497. Epub 2017 Jul 13.
Purpose To demonstrate that anti-MG1 conjugated hybrid magnetic gold nanoparticles (HNPs) act as a catalyst during photothermal ablation (PTA) of colorectal liver metastases, and thus increase ablation zones. Materials and Methods All experiments were performed with approval of the institutional animal care and use committee. Therapeutic and diagnostic multifunctional HNPs conjugated with anti-MG1 monoclonal antibodies were synthesized, and the coupling efficiency was determined. Livers of 19 Wistar rats were implanted with 5 × 10 rat colorectal liver metastasis cell line cells. The rats were divided into three groups according to injection: anti-MG1-coupled HNPs (n = 6), HNPs only (n = 6), and cells only (control group, n = 7). Voxel-wise R2 and R2* magnetic resonance (MR) imaging measurements were obtained before, immediately after, and 24 hours after injection. PTA was then performed with a fiber-coupled near-infrared (808 nm) diode laser with laser power of 0.56 W/cm for 3 minutes, while temperature changes were measured. Tumors were assessed for necrosis with hematoxylin-eosin staining. Organs were analyzed with inductively coupled plasma mass spectrometry to assess biodistribution. Therapeutic efficacy and tumor necrosis area were compared by using a one-way analysis of variance with post hoc analysis for statistically significant differences. Results The coupling efficiency was 22 μg/mg (55%). Significant differences were found between preinfusion and 24-hour postinfusion measurements of both T2 (repeated measures analysis of variance, P = .025) and T2* (P < .001). Significant differences also existed for T2* measurements between the anti-MG1 HNP and HNP-only groups (P = .034). Mean temperature ± standard deviation with PTA in the anti-MG1-coated HNP, HNP, and control groups was 50.2°C ± 7.8, 51°C ± 4.4, and 39.5°C ± 2.0, respectively. Inductively coupled plasma mass spectrometry revealed significant tumor targeting and splenic sequestration. Mean percentages of tumor necrosis in the anti-MG1-coated HNP, HNP, and control groups were 38% ± 29, 14% ± 17, and 7% ± 8, respectively (P = .043). Conclusion Targeted monoclonal antibody-conjugated HNPs can serve as a catalyst for photothermal ablation of colorectal liver metastases by increasing ablation zones. RSNA, 2017.
目的 证明抗MG1偶联的混合磁性金纳米颗粒（HNP）在结直肠癌肝转移灶的光热消融（PTA）过程中起到催化剂的作用，从而扩大消融区域。材料与方法 所有实验均在机构动物护理和使用委员会批准下进行。合成了与抗MG1单克隆抗体偶联的治疗和诊断多功能HNP，并测定了偶联效率。将5×10个大鼠结直肠癌肝转移细胞系细胞植入19只Wistar大鼠的肝脏。根据注射情况将大鼠分为三组：抗MG1偶联的HNP组（n = 6）、仅HNP组（n = 6）和仅细胞组（对照组，n = 7）。在注射前、注射后即刻和注射后24小时进行体素层面的R2和R2磁共振（MR）成像测量。然后用光纤耦合近红外（808 nm）二极管激光进行PTA，激光功率为0.56 W/cm²持续3分钟，同时测量温度变化。用苏木精-伊红染色评估肿瘤坏死情况。用感应耦合等离子体质谱分析法分析器官以评估生物分布。采用单因素方差分析及事后分析比较治疗效果和肿瘤坏死面积的统计学显著差异。结果 偶联效率为22 μg/mg（55%）。T2（重复测量方差分析，P = 0.025）和T2（P < 0.001）的输注前和输注后24小时测量值之间存在显著差异。抗MG1 HNP组和仅HNP组之间的T2*测量值也存在显著差异（P = 0.034）。抗MG1包被的HNP组、HNP组和对照组在PTA时的平均温度±标准差分别为50.2°C±7.8、51°C±4.4和39.5°C±2.0。感应耦合等离子体质谱显示肿瘤有显著靶向性和脾脏潴留。抗MG1包被的HNP组、HNP组和对照组的肿瘤坏死平均百分比分别为38%±29、14%±17和7%±8（P = 0.043）。结论 靶向单克隆抗体偶联的HNP可通过扩大消融区域作为结直肠癌肝转移灶光热消融的催化剂。RSNA，2017年。
