Dai Yunpeng, Chen Duofang, Wang Guodong, Yin Jipeng, Zhan Yonghua, Wu Kaichun, Liang Jimin, Chen Xueli
Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education & School of Life Science and Technology, Xidian University, Xi'an 710071, China.
State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Quant Imaging Med Surg. 2020 Feb;10(2):389-396. doi: 10.21037/qims.2020.01.01.
Bioluminescence imaging (BLI) has been found to have diverse applications in the life sciences and medical research due to its ease of use and high sensitivity. From kinetics analysis, dynamic imaging studies have significant advantages for diagnosis when compared to traditional static imaging studies. This work focuses on modeling and quantitatively analyzing the dynamic data produced from the intraperitoneal (IP) injection of D-luciferin in longitudinal BLI, aiming to provide a powerful tool for monitoring the growth of tumors.
We constructed a three-compartment pharmacokinetic (PK) model and employed the standard Michaelis-Menten (M-M) kinetics to investigate the dynamic BLI data produced from the IP injection of D-luciferin. The 3 compartments were the plasma compartment, the non-specific compartment, and the specific compartment. The validity of this PK model was tested by the dynamic BLI data of MKN28M-luc xenograft mice, along with the published longitudinal dynamic BLI data of B16F10-luc xenograft mice.
The R-squares between the simulated lines and the measurement were 1 and 0.99, respectively, for the mice data and the published data. In addition, the 2 kinetic macroparameters obtained reflected the rate of tumor growth . In particular, the values of macroparameters A showed a significant dependence on tumor surface area.
The proposed PK model may be an effective tool for use in drug development programs and for monitoring the response of tumors to treatment.
由于生物发光成像（BLI）使用简便且灵敏度高，已发现在生命科学和医学研究中有多种应用。从动力学分析来看，与传统静态成像研究相比，动态成像研究在诊断方面具有显著优势。这项工作重点在于对纵向BLI中腹腔注射D - 荧光素产生的动态数据进行建模和定量分析，旨在为监测肿瘤生长提供一个有力工具。
我们构建了一个三室药代动力学（PK）模型，并采用标准的米氏（M - M）动力学来研究腹腔注射D - 荧光素产生的动态BLI数据。这三个室分别是血浆室、非特异性室和特异性室。通过MKN28M - luc异种移植小鼠的动态BLI数据以及已发表的B16F10 - luc异种移植小鼠的纵向动态BLI数据来检验该PK模型的有效性。
对于小鼠数据和已发表数据，模拟线与测量值之间的决定系数（R平方）分别为1和0.99。此外，获得的两个动力学宏观参数反映了肿瘤生长速率。特别是，宏观参数A的值对肿瘤表面积有显著依赖性。
所提出的PK模型可能是药物开发项目以及监测肿瘤对治疗反应的有效工具。
