Yaghoubi Shahriar S, Gambhir Sanjiv S
Bio-X Program, Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Clark Center, 318 Campus Drive, E150, Stanford, CA 94305-5427, USA.
Nat Protoc. 2006;1(6):3069-75. doi: 10.1038/nprot.2006.459.
The herpes simplex virus type 1 thymidine kinase (HSV1-tk) positron emission tomography (PET) reporter gene (PRG) or its mutant HSV1-sr39tk are used to investigate intracellular molecular events in cultured cells and to image intracellular molecular events and cell trafficking in living subjects. The expression of these PRGs can be imaged using 18F- or 124I-radiolabeled acycloguanosine or pyrimidine analog PET reporter probes (PRPs). This protocol describes the procedures for imaging HSV1-tk or HSV1-sr39tk PRG expression in living subjects with the acycloguanosine analog 9-4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG). [18F]FHBG is a high-affinity substrate for the HSV1-sr39TK enzyme with relatively low affinity for mammalian TK enzymes, resulting in improved detection sensitivity. Furthermore, [18F]FHBG is approved by the US Food and Drug Administration as an investigational new imaging agent and has been shown to detect HSV1-tk transgene expression in the liver tumors of patients. MicroPET imaging of each small animal can be completed in approximately 1.5 h, and each patient imaging session takes approximately 3 h.
单纯疱疹病毒1型胸苷激酶（HSV1 - tk）正电子发射断层扫描（PET）报告基因（PRG）或其突变体HSV1 - sr39tk用于研究培养细胞中的细胞内分子事件，以及对活体受试者体内的细胞内分子事件和细胞转运进行成像。这些PRG的表达可以使用18F或124I放射性标记的无环鸟苷或嘧啶类似物PET报告探针（PRP）进行成像。本方案描述了使用无环鸟苷类似物9 - [4 - [18F]氟 - 3 -（羟甲基）丁基]鸟嘌呤（[18F]FHBG）对活体受试者中HSV1 - tk或HSV1 - sr39tk PRG表达进行成像的程序。[18F]FHBG是HSV1 - sr39TK酶的高亲和力底物，对哺乳动物TK酶的亲和力相对较低，从而提高了检测灵敏度。此外，[18F]FHBG已被美国食品药品监督管理局批准作为一种研究性新型成像剂，并已被证明可检测患者肝肿瘤中的HSV1 - tk转基因表达。每只小动物的微型PET成像大约可在1.5小时内完成，每次患者成像检查大约需要3小时。
