用于区分肿瘤与炎症的σ配体和代谢型PET示踪剂的比较

Comparison of sigma-ligands and metabolic PET tracers for differentiating tumor from inflammation.

作者信息

van Waarde Aren, Jager Pieter L, Ishiwata Kiichi, Dierckx Rudi A, Elsinga Philip H

机构信息

Department of Nuclear Medicine and Molecular Imaging, University Medical Center of Groningen, University of Groningen, The Netherlands.

出版信息

J Nucl Med. 2006 Jan;47(1):150-4.

PMID:16391199

Abstract

UNLABELLED

Novel radiopharmaceuticals for the detection of tumors and their metastases may be of clinical interest if they are more tumor selective than (18)F-FDG. Increased glucose metabolism of inflammatory tissues is the main source of false-positive (18)F-FDG PET findings in oncology.

METHODS

We compared the biodistribution of 4 PET tracers (2 sigma-receptor ligands, (11)C-choline, and (11)C-methionine) with previously published biodistribution data of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) and of (18)F-FDG in the same animal model. The model consisted of male 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 of PET tracer (approximately 30 MBq in the case of (18)F and 74 MBq for (11)C).

RESULTS

(18)F-FDG showed the highest tumor-to-muscle ratio of all radiopharmaceuticals (13.2 +/- 3.0, mean +/- SD), followed at a large distance by the sigma-1 ligand (11)C-SA4503 (5.1 +/- 1.7), (18)F-FLT (3.8 +/- 1.3), the non-subtype-selective sigma-ligand (18)F-FE-SA5845 (3.3 +/- 1.5), (11)C-choline (3.1 +/- 0.4), and (11)C-methionine (2.8 +/- 0.3). sigma-Ligands and (18)F-FLT were relatively tumor selective ((18)F-FE-SA5845, greater than 30-fold; (11)C-SA4503 and (18)F-FLT, greater than 10-fold). The tumor selectivity of (11)C-methionine was only slightly better than that of (18)F-FDG. (11)C-Choline showed equal uptake in tumor and inflammation. All tracers were avidly taken up by proliferative tissue (small intestine, bone marrow). High physiologic uptake of some compounds was observed in brain, heart, lung, pancreas, spleen, and salivary gland.

CONCLUSION

sigma-Ligands and (18)F-FLT were more tumor selective than (18)F-FDG, (11)C-choline, or (11)C-methionine in our animal model. However, these novel radiopharmaceuticals were less sensitive than were the established oncologic tracers.

摘要

未标注

如果新型放射性药物比（18）F-FDG对肿瘤更具选择性，那么它们对于肿瘤及其转移灶的检测可能具有临床意义。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。

方法

我们将4种PET示踪剂（2种σ受体配体、（11）C-胆碱和（11）C-蛋氨酸）的生物分布与先前发表的在同一动物模型中3'-脱氧-3'-（18）F-氟胸苷（（18）F-FLT）和（18）F-FDG的生物分布数据进行了比较。该模型由雄性Wistar大鼠组成，这些大鼠右肩部有肿瘤（C6大鼠胶质瘤），左小腿肌肉有无菌性炎症（通过注射0.1 mL松节油诱导）。松节油注射24小时后，大鼠静脉推注PET示踪剂（对于（18）F约为30 MBq，对于（11）C为74 MBq）。

结果

（18）F-FDG在所有放射性药物中显示出最高的肿瘤与肌肉比值（13.2±3.0，平均值±标准差），其次是σ-1配体（11）C-SA4503（5.1±1.7），相差较大，然后是（18）F-FLT（3.8±1.3）、非亚型选择性σ配体（18）F-FE-SA5845（3.3±1.5）、（11）C-胆碱（3.1±0.4）和（11）C-蛋氨酸（2.8±0.3）。σ配体和（18）F-FLT相对具有肿瘤选择性（（18）F-FE-SA5845大于30倍；（11）C-SA4503和（18）F-FLT大于10倍）。（11）C-蛋氨酸的肿瘤选择性仅略优于（18）F-FDG。（11）C-胆碱在肿瘤和炎症中的摄取相同。所有示踪剂都被增殖组织（小肠、骨髓）大量摄取。在脑、心脏、肺、胰腺、脾脏和唾液腺中观察到一些化合物的生理性高摄取。