Mueller Romy, Moreau Michele, Yasmin-Karim Sayeda, Protti Andrea, Tillement Olivier, Berbeco Ross, Hesser Jürgen, Ngwa Wilfred
Department Data Analysis and Modeling in Medicine, Mannheim Institute for Intelligent Systems in Medicine (MIISM), Heidelberg University, 69117 Heidelberg, Germany.
Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Nanomaterials (Basel). 2020 Nov 13;10(11):2249. doi: 10.3390/nano10112249.
Smart radiotherapy biomaterials (SRBs) present a new opportunity to enhance image-guided radiotherapy while replacing routinely used inert radiotherapy biomaterials like fiducials. In this study the potential of SRBs loaded with gadolinium-based nanoparticles (GdNPs) is investigated for magnetic resonance imaging (MRI) contrast. GdNP release from SRB is quantified and modelled for accurate prediction. SRBs were manufactured similar to fiducials, with a cylindrical shell consisting of poly(lactic-co-glycolic) acid (PLGA) and a core loaded with GdNPs. Magnetic resonance imaging (MRI) contrast was investigated at 7T in vitro (in agar) and in vivo in subcutaneous tumors grown with the LLC1 lung cancer cell line in C57/BL6 mice. GdNPs were quantified in-phantom and in tumor and their release was modelled by the Weibull distribution. Gd concentration was linearly fitted to the R relaxation rate with a detection limit of 0.004 mmol/L and high confidence level (R = 0.9843). GdNP loaded SRBs in tumor were clearly visible up to at least 14 days post-implantation. Signal decrease during this time showed GdNP release in vivo, which was calculated as 3.86 ± 0.34 µg GdNPs release into the tumor. This study demonstrates potential and feasibility for SRBs with MRI-contrast, and sensitive GdNP quantification and release from SRBs in a preclinical animal model. The feasibility of monitoring nanoparticle (NP) concentration during treatment, allowing dynamic quantitative treatment planning, is also discussed.
智能放射治疗生物材料（SRB）为增强图像引导放射治疗提供了新机会，同时可替代像基准标记这类常规使用的惰性放射治疗生物材料。在本研究中，对负载钆基纳米颗粒（GdNP）的SRB用于磁共振成像（MRI）造影的潜力进行了研究。对SRB中GdNP的释放进行了定量和建模，以实现准确预测。SRB的制造类似于基准标记，具有由聚（乳酸-共-乙醇酸）（PLGA）组成的圆柱形外壳以及负载GdNP的核心。在7T场强下，在体外（琼脂中）以及在C57/BL6小鼠中用LLC1肺癌细胞系培养的皮下肿瘤体内研究了MRI造影。在体模和肿瘤中对GdNP进行了定量，并通过威布尔分布对其释放进行了建模。Gd浓度与R弛豫率呈线性拟合，检测限为0.004 mmol/L，置信水平高（R = 0.9843）。植入后至少14天内，肿瘤中负载GdNP的SRB清晰可见。在此期间信号下降表明GdNP在体内释放，计算得出释放到肿瘤中的GdNP量为3.86±0.34μg。本研究证明了具有MRI造影功能的SRB的潜力和可行性，以及在临床前动物模型中对SRB中GdNP进行灵敏定量和释放研究的可行性。还讨论了在治疗过程中监测纳米颗粒（NP）浓度以实现动态定量治疗计划的可行性。
