αvβ3 选择性示踪剂 18F-半乳糖-RGD 在癌症患者中的生物分布及药代动力学

Biodistribution and pharmacokinetics of the alphavbeta3-selective tracer 18F-galacto-RGD in cancer patients.

作者信息

Beer Ambros J, Haubner Roland, Goebel Michael, Luderschmidt Stephan, Spilker Mary E, Wester Hans-Jürgen, Weber Wolfgang A, Schwaiger Markus

机构信息

Department of Nuclear Medicine, Technische Universität München, Germany.

出版信息

J Nucl Med. 2005 Aug;46(8):1333-41.

PMID:16085591

Abstract

UNLABELLED

(18)F-Galacto-RGD has been developed for PET of alpha(v)beta(3) integrin expression, a receptor involved in, for example, angiogenesis and metastasis. Our aim was to study the kinetics and biodistribution of (18)F-Galacto-RGD in cancer patients.

METHODS

Nineteen patients with metastases of malignant melanoma (n = 7), sarcomas (n = 10), or osseous metastases (n = 2) were examined. After injection of 133-200 MBq (18)F-Galacto-RGD, 3 consecutive emission scans from the pelvis to the thorax or dynamic emission scans of the tumor over 60 min, followed by 1 static emission scan of the body, were acquired. Time-activity curves and standardized uptake values (SUVs) were derived by image region-of-interest analysis with image-based arterial input functions. Compartmental modeling was used to derive the distribution volume for muscle tissue and tumors.

RESULTS

(18)F-Galacto-RGD showed rapid blood clearance and primarily renal excretion. SUVs in tumors ranged from 1.2 to 9.0. Tumor-to-blood and tumor-to-muscle ratios increased over time, with peak ratios of 3.1 +/- 2.0 and 7.7 +/- 4.3, respectively, at 72 min. The tumor kinetics were consistent with a 2-tissue compartment model with reversible specific binding. Distribution volume values were, on average, 4 times higher for tumor tissue (1.5 +/- 0.8) than those for muscle tissue (0.4 +/- 0.1). The data suggest that there was only minimal free and bound (specific or nonspecific) tracer in muscle tissue.

CONCLUSION

(18)F-Galacto-RGD demonstrates a highly favorable biodistribution in humans with specific receptor binding. Most important, this study shows that (18)F-Galacto-RGD allows visualization of alpha(v)beta(3) expression in tumors with high contrast. Consequently, this tracer offers a new strategy for noninvasive monitoring of molecular processes and may supply helpful information for planning and controlling of therapeutic approaches targeting the alpha(v)beta(3) integrin.

摘要

未标记

（18）F-半乳糖-RGD已被开发用于正电子发射断层显像（PET）检测α（v）β（3）整合素的表达，该受体参与例如血管生成和转移过程。我们的目的是研究（18）F-半乳糖-RGD在癌症患者体内的动力学和生物分布。

方法

对19例患有恶性黑色素瘤转移（n = 7）、肉瘤转移（n = 10）或骨转移（n = 2）的患者进行检查。注射133 - 200 MBq的（18）F-半乳糖-RGD后，进行从骨盆到胸部的连续3次发射扫描或对肿瘤进行60分钟的动态发射扫描，随后进行一次全身静态发射扫描。通过基于图像的动脉输入函数的图像感兴趣区域分析得出时间-活性曲线和标准化摄取值（SUV）。采用房室模型推导肌肉组织和肿瘤的分布容积。

结果

（18）F-半乳糖-RGD显示出血液清除迅速且主要经肾脏排泄。肿瘤的SUV范围为1.2至9.0。肿瘤与血液及肿瘤与肌肉的比值随时间增加，在72分钟时峰值比值分别为3.1±2.0和7.7±4.3。肿瘤动力学符合具有可逆特异性结合的双组织房室模型。肿瘤组织的分布容积值平均比肌肉组织高4倍（分别为1.5±0.8和0.4±0.1）。数据表明肌肉组织中游离和结合（特异性或非特异性）示踪剂极少。

结论

（18）F-半乳糖-RGD在人体内显示出高度良好的生物分布并具有特异性受体结合。最重要的是，本研究表明（18）F-半乳糖-RGD能够以高对比度显示肿瘤中的α（v）β（3）表达。因此，这种示踪剂为分子过程的无创监测提供了一种新策略，并可能为针对α（v）β（3）整合素的治疗方法的规划和控制提供有用信息。