van Waarde Aren, Cobben David C P, Suurmeijer Albert J H, Maas Bram, Vaalburg Willem, de Vries Erik F J, Jager Pieter L, Hoekstra Harald J, Elsinga Philip H
PET Center, Groningen University Hospital, Groningen, The Netherlands.
J Nucl Med. 2004 Apr;45(4):695-700.
Increased glucose metabolism of inflammatory tissues is the main source of false-positive (18)F-FDG PET findings in oncology. It has been suggested that radiolabeled nucleosides might be more tumor specific.
To test this hypothesis, we compared the biodistribution of 3'-deoxy-3'-(18)F-fluorothymidine (FLT) and (18)F-FDG in Wistar rats that bore tumors (C6 rat glioma in the right shoulder) and also had sterile inflammation in the left calf muscle (induced by injection of 0.1 mL of turpentine). Twenty-four hours after turpentine injection, the rats received an intravenous bolus (30 MBq) of either (18)F-FLT (n = 5) or (18)F-FDG (n = 5). Pretreatment of the animals with thymidine phosphorylase (>1,000 U/kg, intravenously) before injection of (18)F-FLT proved to be necessary to reduce the serum levels of endogenous thymidine and achieve satisfactory tumor uptake of radioactivity.
Tumor-to-muscle ratios of (18)F-FDG at 2 h after injection (13.2 +/- 3.0) were higher than those of (18)F-FLT (3.8 +/- 1.3). (18)F-FDG showed high physiologic uptake in brain and heart, whereas (18)F-FLT was avidly taken up by bone marrow. (18)F-FDG accumulated in the inflamed muscle, with 4.8 +/- 1.2 times higher uptake in the affected thigh than in the contralateral healthy thigh, in contrast to (18)F-FLT, for which this ratio was not significantly different from unity (1.3 +/- 0.4).
In (18)F-FDG PET images, both tumor and inflammation were visible, but (18)F-FLT PET showed only the tumor. Thus, the hypothesis that (18)F-FLT has a higher tumor specificity was confirmed in our animal model.
炎症组织中葡萄糖代谢增加是肿瘤学中(18)F-FDG PET假阳性结果的主要来源。有人提出放射性标记的核苷可能对肿瘤更具特异性。
为验证这一假设,我们比较了3'-脱氧-3'-(18)F-氟胸苷(FLT)和(18)F-FDG在荷瘤(右肩部C6大鼠胶质瘤)且左小腿肌肉有无菌性炎症(通过注射0.1 mL松节油诱导)的Wistar大鼠体内的生物分布。松节油注射24小时后,大鼠静脉推注(30 MBq)(18)F-FLT(n = 5)或(18)F-FDG(n = 5)。在注射(18)F-FLT前用胸苷磷酸化酶(>1000 U/kg,静脉注射)预处理动物被证明是必要的,以降低内源性胸苷的血清水平并实现放射性在肿瘤中的满意摄取。
注射后2小时(18)F-FDG的肿瘤与肌肉比值(13.2±3.0)高于(18)F-FLT(3.8±1.3)。(18)F-FDG在脑和心脏中显示出高生理性摄取,而(18)F-FLT被骨髓大量摄取。(18)F-FDG在炎症肌肉中蓄积,患侧大腿的摄取量比健侧大腿高4.8±1.2倍,相比之下,(18)F-FLT的该比值与1无显著差异(1.3±0.4)。
在(18)F-FDG PET图像中,肿瘤和炎症均可见,但(18)F-FLT PET仅显示肿瘤。因此,(18)F-FLT具有更高肿瘤特异性的假设在我们建立的动物模型中得到了证实。