Parashurama Natesh, Ahn Byeong-Cheol, Ziv Keren, Ito Ken, Paulmurugan Ramasamy, Willmann Jürgen K, Chung Jaehoon, Ikeno Fumiaki, Swanson Julia C, Merk Denis R, Lyons Jennifer K, Yerushalmi David, Teramoto Tomohiko, Kosuge Hisanori, Dao Catherine N, Ray Pritha, Patel Manishkumar, Chang Ya-Fang, Mahmoudi Morteza, Cohen Jeff Eric, Goldstone Andrew Brooks, Habte Frezghi, Bhaumik Srabani, Yaghoubi Shahriar, Robbins Robert C, Dash Rajesh, Yang Phillip C, Brinton Todd J, Yock Paul G, McConnell Michael V, Gambhir Sanjiv S
From the Department of Radiology, James Clark Center, Molecular Imaging Program at Stanford, 318 Campus Drive West, Room E153, Stanford University, Stanford, CA 94305 (N.P., K.Z., K.I., R.P., J.K.W., D.Y., M.P., Y.F.C., F.H., S.Y., S.S.G.); Department of Cardiovascular Medicine (J.C., F.I., J.K.L., T.T., H.K., C.N.D., M.M., R.D., P.C.Y., T.J.B., P.G.Y., M.V.M.), Department of Cardiothoracic Surgery (J.C.S., D.R.M., J.E.C., A.B.G., R.C.R.), Department of Bioengineering (D.Y., P.G.Y., S.S.G.), Canary Center for Early Detection of Cancer (R.P., S.S.G.), and Department of Materials Science and Engineering (S.S.G.), Stanford University, Stanford, Calif; GE Global Research Center, General Electric, Niskayuna, NY (S.B.); Department of Nuclear Medicine, Kyungpook National University, Daegu, South Korea (B.C.A.); and Advanced Center for Treatment, Research, and Education ACTREC, Tata Memorial Centre, Navi Mumbai, India (P.R.).
Radiology. 2016 Sep;280(3):826-36. doi: 10.1148/radiol.2016151150. Epub 2016 Jun 22.
Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone. Clinical MR imaging and PET reporter gene molecular imaging were performed after intravenous injection of the radiotracer fluorine 18-radiolabeled 9-[4-fluoro-3-(hydroxyl methyl) butyl] guanine ((18)F-FHBG). Linear regression analysis of both MR imaging and PET data and nonlinear regression analysis of PET data were performed, accounting for multiple injections per animal. Results MR imaging showed a positive correlation between MSC-TF-NP cell number and dephasing (dark) signal (R(2) = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 × 10(7) cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R(2) = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R(2) = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 × 10(8) cells. Conclusion The authors quantitatively determined the limit of detection of MSC after CCT in swine by using clinical PET reporter gene imaging and clinical MR imaging with cell prelabeling. (©) RSNA, 2016 Online supplemental material is available for this article.
目的 通过使用临床正电子发射断层扫描（PET）报告基因成像和细胞预标记的磁共振（MR）成像，定量测定猪心脏细胞治疗（CCT）后骨髓基质细胞（MSC）的检测限。材料与方法 动物研究经机构实验动物护理管理小组批准。7头猪接受了23次心内细胞注射，注射物包含对照MSC以及表达多模态三重融合（TF）报告基因的MSC（MSC-TF）与携带超顺磁性氧化铁纳米颗粒（NP）的细胞混合物（MSC-TF-NP）或仅含NP。静脉注射放射性示踪剂氟18标记的9-[4-氟-3-（羟甲基）丁基]鸟嘌呤（（18）F-FHBG）后进行临床MR成像和PET报告基因分子成像。对MR成像和PET数据进行线性回归分析，并对PET数据进行非线性回归分析，同时考虑每只动物的多次注射情况。结果 MR成像显示MSC-TF-NP细胞数量与去相位（暗）信号之间呈正相关（R（2） = 0.72，P = .0001），检测下限至少约为1.5×10（7）个细胞。PET报告基因成像显示，线性模型（R（2） = 0.88，P = .0001，均方根误差 = 0.523）和非线性模型（R（2） = 0.99，P = .0001，均方根误差 = 0.273）下，MSC-TF与靶本比之间存在显著正相关，检测下限为2.5×10（8）个细胞。结论 作者通过使用临床PET报告基因成像和细胞预标记的临床MR成像，定量测定了猪CCT后MSC的检测限。（©）RSNA，2016 本文有在线补充材料。
