Nyström Nivin N, Yip Lawrence C M, Carson Jeffrey J L, Scholl Timothy J, Ronald John A
Department of Medical Biophysics, University of Western Ontario, 1151 Richmond St N, Room 2241A, London, ON, Canada N6A 3K7 (N.N.N., L.C.M.Y., J.J.L.C., T.J.S., J.A.R.); Imaging Research Laboratories, Robarts Research Institute, London, Canada (N.N.N., T.J.S., J.A.R.); Lawson Health Research Institute, London, Canada (L.C.M.Y., J.J.L.C., J.A.R.); and Ontario Institute for Cancer Research, Toronto, Canada (T.J.S.).
Radiol Imaging Cancer. 2019 Nov 29;1(2):e190035. doi: 10.1148/rycan.2019190035. eCollection 2019 Nov.
To develop a photoacoustic imaging (PAI) reporter gene that has high translational potential. Previous research has shown that human organic anion-transporting polypeptide 1b3 (OATP1B3) promotes the uptake of the near-infrared fluorescent dye indocyanine green (ICG). In this study, the authors have established and ICG as a reporter gene-probe pair for in vivo PAI.
Human breast cancer cells were engineered to express . Control cells (not expressing ) or -expressing cells were incubated with or without ICG, placed in a breast-mimicking phantom, and imaged with PAI. Control ( = 6) or -expressing ( = 5) cells were then implanted orthotopically into female mice. Full-spectrum PAI was performed before and 24 hours after ICG administration. One-way analysis of variance was performed, followed by Tukey posthoc multiple comparisons, to assess statistical significance.
-expressing cells incubated with ICG exhibited a 2.7-fold increase in contrast-to-noise ratio relative to all other controls in vitro ( < .05). In mice, PAI signals after ICG administration were increased 2.3-fold in OATP1B3 tumors relative to those in controls ( < .05).
operates as an in vivo PAI reporter gene based on its ability to promote the cellular uptake of ICG. Benefits include the human derivation of , combined with the use of wavelengths in the near-infrared region, high extinction coefficient, low quantum yield, and clinical approval of ICG. The authors posit that this system will be useful for localized monitoring of emerging gene- and cell-based therapies in clinical applications.© RSNA, 2019 Animal Studies, Molecular Imaging, Molecular Imaging-Clinical Translation, Molecular Imaging-Reporter Gene Imaging, Optical Imaging
开发一种具有高转化潜力的光声成像（PAI）报告基因。先前的研究表明，人类有机阴离子转运多肽1b3（OATP1B3）可促进近红外荧光染料吲哚菁绿（ICG）的摄取。在本研究中，作者已将OATP1B3和ICG确立为用于体内PAI的报告基因-探针组对。
对人乳腺癌细胞进行工程改造以表达OATP1B3。将对照细胞（不表达OATP1B3）或表达OATP1B3的细胞与ICG一起或不与ICG一起孵育，置于模拟乳房的体模中，并用PAI进行成像。然后将对照（n = 6）或表达OATP1B3（n = 5）的细胞原位植入雌性小鼠体内。在给予ICG之前和之后24小时进行全谱PAI。进行单因素方差分析，随后进行Tukey事后多重比较，以评估统计学意义。
与ICG一起孵育的表达OATP1B3的细胞在体外相对于所有其他对照的对比噪声比增加了2.7倍（P <.05）。在小鼠中，给予ICG后的PAI信号在OATP1B3肿瘤中相对于对照增加了2.3倍（P <.05）。
基于其促进细胞摄取ICG的能力，OATP1B3可作为体内PAI报告基因发挥作用。优点包括OATP1B3来源于人类，同时使用近红外区域的波长、高消光系数、低量子产率以及ICG的临床批准。作者认为该系统将有助于在临床应用中对新兴的基于基因和细胞的疗法进行局部监测。©RSNA，2019动物研究、分子成像、分子成像临床转化、分子成像报告基因成像、光学成像
