Hustinx R, Shiue C Y, Alavi A, McDonald D, Shiue G G, Zhuang H, Lanuti M, Lambright E, Karp J S, Eck S L
Department of Radiology, University of Pennsylvania, Philadelphia, USA.
Eur J Nucl Med. 2001 Jan;28(1):5-12. doi: 10.1007/s002590000396.
Radiolabelled ganciclovir analogues have shown promise as imaging agents to detect herpes simplex virus thymidine kinase (HSVtk) expression. This study evaluated the use of positron emission tomography (PET) imaging with 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG) to assess gene transfer into tumours. HSVtk-positive and HSVtk-negative cell lines were first treated in vitro with [18F]FHPG. To assess the efficacy of PET in detecting HSVtk expression following in vivo gene transfer, mice were injected intravenously with an adenovirus encoding HSVtk (Ad.HSVtk), a control vector (Ad.Bgl2) or saline. Subcutaneous human glioma xenografts were grown in mice and treated by direct injection of Ad.HSVtk or Ad.Bgl2. Imaging was performed 48 h after transduction. Similar experiments were performed using Fischer rats implanted with syngeneic tumours. The presence of the HSVtk protein was confirmed by immunohistochemistry. Biodistribution studies were also obtained in 14 naive mice. In vitro studies showed high and specific uptake of [18F]FHPG in HSVtk-positive cell lines, with an uptake ratio of up to 27:1. PET imaging and direct counting of major organs demonstrated HSVtk-specific tracer retention. In mice, HSVtk-positive tumours retained 3.4% dose/gram as compared to 0.6% for control tumours (P=0.03). They were clearly seen on the PET images as early as 100 min post injection. Similar results were obtained with syngeneic rat tumours. Biodistribution studies demonstrated the rapid distribution and clearance of the tracer in all major organs. Our results demonstrate that PET imaging of HSVtk gene transfer to tumours is feasible and is highly specific for HSVtk expression.
放射性标记的更昔洛韦类似物已显示出作为检测单纯疱疹病毒胸苷激酶（HSVtk）表达的成像剂的潜力。本研究评估了使用正电子发射断层扫描（PET）成像结合9-[(3-[¹⁸F]氟-1-羟基-2-丙氧基)甲基]鸟嘌呤（[¹⁸F]FHPG）来评估基因向肿瘤的转移。首先在体外使用[¹⁸F]FHPG处理HSVtk阳性和HSVtk阴性细胞系。为了评估PET在体内基因转移后检测HSVtk表达的功效，给小鼠静脉注射编码HSVtk的腺病毒（Ad.HSVtk）、对照载体（Ad.Bgl2）或生理盐水。在小鼠体内皮下接种人胶质瘤异种移植物，并通过直接注射Ad.HSVtk或Ad.Bgl2进行处理。转导后48小时进行成像。使用植入同基因肿瘤的Fischer大鼠进行了类似实验。通过免疫组织化学确认了HSVtk蛋白的存在。还在14只未处理的小鼠中进行了生物分布研究。体外研究表明，[¹⁸F]FHPG在HSVtk阳性细胞系中具有高特异性摄取，摄取率高达27:1。PET成像和主要器官的直接计数显示了HSVtk特异性示踪剂滞留。在小鼠中，HSVtk阳性肿瘤每克保留3.4%的剂量，而对照肿瘤为0.6%（P = 0.03）。在注射后100分钟，它们在PET图像上就清晰可见。同基因大鼠肿瘤也获得了类似结果。生物分布研究表明示踪剂在所有主要器官中迅速分布和清除。我们的结果表明，对肿瘤进行HSVtk基因转移的PET成像可行，且对HSVtk表达具有高度特异性。
