在R1M横纹肌肉瘤无胸腺小鼠模型中对123/125I-2-碘-L-苯丙氨酸作为单光子发射计算机断层扫描（SPECT）潜在肿瘤示踪剂的体内特性研究。

In vivo characterization of 123/125I-2-iodo-L-phenylalanine in an R1M rhabdomyosarcoma athymic mouse model as a potential tumor tracer for SPECT.

作者信息

Kersemans Veerle, Cornelissen Bart, Kersemans Ken, Bauwens Matthias, Achten Erik, Dierckx Rudi A, Mertens John, Slegers Guido

机构信息

Laboratory for Radiopharmacy, Universiteit Gent, Gent, Belgium.

出版信息

J Nucl Med. 2005 Mar;46(3):532-9.

PMID:15750170

Abstract

UNLABELLED

The application of 123I-3-iodo-alpha-methyltyrosine is limited to diagnosis of brain tumors due to its marked long-term uptake in kidneys. In vitro evaluation of 125I-2-iodo-L-phenylalanine showed high uptake in R1M cells by L-type amino acid transport system 1 (LAT1). This study evaluates 123I-2-iodo-L-phenylalanine as a new specific tumor tracer for SPECT.

METHODS

123/125I-2-Iodo-L-phenylalanine is prepared as a one-pot kit using the Cu1+-assisted isotopic exchange method. The characteristics of 125I-2-iodo-L-phenylalanine were examined in vivo in R1M tumor-bearing athymic mice and in acute inflammation-bearing NMRI mice. The uptake of 123/125I-2-iodo-L-phenylalanine in tumor and other organs of interest was measured by dynamic planar imaging (DPI) and gamma-counting after dissection. Displacement of 123I-2-iodo-L-phenylalanine radioactivity by L-phenylalanine, L-methionine, and L-cysteine was measured. 123I-Iodo-human serum albumin planar imaging was performed to correct for blood-pool activity and MRI was performed to delineate the tumor in DPI. 18F-FDG uptake was measured with an animal PET scanner. 125I-2-Iodo-L-phenylalanine and 18F-FDG uptake in inflamed muscle were compared.

RESULTS

123/125I-2-Iodo-L-phenylalanine showed a high and fast tumor uptake and followed a reversible first-order pattern allowing calculation of the half-life and the time to reach equilibrium (t(R)). Net tumor-to-background ratios up to 6.7 at 60 min were obtained. This radioactivity was significantly displaced by L-phenylalanine, L-methionine, and L-cysteine, pointing to reversible LAT transport. When plotting t(R) of the tumor uptake as a function of tumor volume, a rectangular hyperbolic curve was obtained. The almost constant t(R) values at higher tumor volumes (>4 mL) could be linked to increased necrotic tissue. Fast blood clearance of the tracer through the kidneys to the bladder and low tracer activity in the abdomen and brain were observed. The inflamed muscle showed only a slight increase of 125I-2-iodo-L-phenylalanine uptake (inflammation-to-background ratio, RIB = 1.30 +/- 0.02), in contrast to the high 18F-FDG uptake (RIB = 11.1 +/- 1.7). The in vivo stability of 123/125I-2-iodo-L-phenylalanine was good: Only 7% of free radioiodide and no other labeled metabolites were observed after 90 min.

CONCLUSION

123/125I-2-Iodo-L-phenylalanine is quickly taken up by the overexpressed LAT1 system in R1M tumors with high tumor specificity. The availability of a kit and the specificity of the tracer make 123I-2-iodo-L-phenylalanine a promising tool for oncologic SPECT.

摘要

未标记

123I - 3 - 碘 - α - 甲基酪氨酸由于在肾脏中有显著的长期摄取，其应用仅限于脑肿瘤的诊断。对125I - 2 - 碘 - L - 苯丙氨酸的体外评估显示，通过L型氨基酸转运系统1（LAT1），其在R1M细胞中有高摄取。本研究评估123I - 2 - 碘 - L - 苯丙氨酸作为一种用于单光子发射计算机断层扫描（SPECT）的新型特异性肿瘤示踪剂。

方法

采用Cu1 + 辅助同位素交换法，将123/125I - 2 - 碘 - L - 苯丙氨酸制备成单瓶试剂盒。在荷R1M肿瘤的无胸腺小鼠和患急性炎症的NMRI小鼠体内研究125I - 2 - 碘 - L - 苯丙氨酸的特性。通过动态平面显像（DPI）和解剖后的γ计数测量123/125I - 2 - 碘 - L - 苯丙氨酸在肿瘤及其他感兴趣器官中的摄取。测量L - 苯丙氨酸、L - 蛋氨酸和L - 半胱氨酸对123I - 2 - 碘 - L - 苯丙氨酸放射性的置换作用。进行123I - 碘人血清白蛋白平面显像以校正血池活性，并进行磁共振成像（MRI）以在DPI中描绘肿瘤。用动物正电子发射断层扫描（PET）扫描仪测量18F - 氟代脱氧葡萄糖（18F - FDG）的摄取。比较125I - 2 - 碘 - L - 苯丙氨酸和18F - FDG在炎症肌肉中的摄取。

结果

123/125I - 2 - 碘 - L - 苯丙氨酸显示出高且快速的肿瘤摄取，并遵循可逆的一级模式，允许计算半衰期和达到平衡的时间（t(R)）。在60分钟时，肿瘤与本底的净比值高达6.7。L - 苯丙氨酸、L - 蛋氨酸和L - 半胱氨酸可显著置换这种放射性，表明是可逆的LAT转运。当将肿瘤摄取的t(R)作为肿瘤体积的函数作图时，得到一条矩形双曲线。在较高肿瘤体积（>4 mL）时，几乎恒定的t(R)值可能与坏死组织增加有关。观察到示踪剂通过肾脏快速清除到膀胱，且在腹部和脑部的示踪剂活性较低。与18F - FDG的高摄取（炎症与本底比值，RIB = 11.1±1.7）相比，炎症肌肉中125I - 2 - 碘 - L - 苯丙氨酸的摄取仅略有增加（RIB = 1.30±0.02）。123/125I - 2 - 碘 - L - 苯丙氨酸的体内稳定性良好：90分钟后仅观察到7%的游离放射性碘，未观察到其他标记代谢物。