Comparison of the uptake of [123/125I]-2-iodo-D-tyrosine and [123/125I]-2-iodo-L-tyrosine in R1M rhabdomyosarcoma cells in vitro and in R1M tumor-bearing Wag/Rij rats in vivo
Comparison of the uptake of [123/125I]-2-iodo-D-tyrosine and [123/125I]-2-iodo-L-tyrosine in R1M rhabdomyosarcoma cells in vitro and in R1M tumor-bearing Wag/Rij rats in vivo
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DOI：
10.1016/j.nucmedbio.2006.05.004
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发表时间：
2006-08-01
影响因子：
3.1
通讯作者：
Meltens, John
中科院分区：
文献类型：
--
作者：
Bauwens, Matthias;Lahoutte, Tony;Meltens, John
简介：最近，关于D-氨基酸在肿瘤中的体内摄取的有希望的结果已经发表。因此，我们决定评估[I-123]-2-碘-L-酪氨酸的D-类似物的肿瘤摄取，这是我们小组最近引入临床试验的示踪剂。2-氨基-3-（4-羟基-2-[（123）/I-125]碘苯基）-D-丙酸在表达LATI的RIM大鼠横纹肌肉瘤细胞中和在携带RIM肿瘤的Wag/Rij大鼠中在体外研究（2-碘-D-酪氨酸）。在适当的缓冲液中测定RIM细胞对[I-125]-2-碘-L-酪氨酸和[I-125]-2-碘-D-酪氨酸的摄取，以研究相关的转运系统。结果：在体外实验条件下，含Na+的HEPES缓冲液中[I-123]-2-iodo-L-tyrosine和[I-125]-2-iodo-D-tyrosine的摄取量比对照组高25%。在不存在Na+离子的情况下，[I-125] -2-碘-D-酪氨酸在RIM细胞中可逆地被摄取，具有明显的蓄积，可能大部分通过LAT 1系统。动态平面显像显示[（123）]-2-碘-D-酪氨酸在肿瘤中的摄取略低于[I-123]-2-碘-L-酪氨酸。在注射后30分钟，L-和D-对映异构体的平均微分摄取比值分别为2.5 - 0.7和1.7 - 0.6。虽然D-异构体的摄取较低，可能是由于从血液中清除较快，但肿瘤背景比与L-类似物相同。大部分（75%）体外[I-125]-2-碘-D-酪氨酸和体内[I-123]-2-碘-D-酪氨酸在RIM肿瘤细胞中通过Na+非依赖性LAT转运系统可逆地高度摄取，更可能是通过LAT 1大鼠血液中[I-123]-2-碘-D-酪氨酸的清除速度快于L-类似物，导致肿瘤摄取略低，但肿瘤-背景比相同。(c)2006年爱思唯尔公司All rights reserved.
Introduction: Recently, promising results concerning uptake in vivo in tumors of D-amino acids have been published. Therefore, we decided to evaluate the tumor uptake of the D-analogue of [I-123]-2-iodo-L-tyrosine, a tracer recently introduced by our group into clinical trials. The uptake of 2-amino-3-(4-hydroxy-2-[(123)/I-125]iodophenyl)-D-propanoic acid (2-iodo-D-tyro sine) was studied in vitro in LATI-expressing RIM rat rhabdomyosarcoma cells and in vivo in RIM tumor-bearing Wag/Rij rats.Methods: The uptake of [I-125]-2-iodo-L-tyrosine and [I-125]-2-iodo-D-tyrosine into RIM cells was determined in appropriate buffers, I allowing the study of the involved transport systems. In vivo, the biodistribution in RIM-bearing rats of [I-123] -2-iodo-L-tyrosine and [I-123]-2-iodo-Dtyrosine was performed by both dynamic and static planar imaging with a gamma camera.Results: In in vitro conditions, the uptake of both [I-125]-2-iodo-L-tyrosine and [1251]-2-iodo-D-tyrosine in the HEPES buffer was 25% higher in the presence of Na ions. In the absence of Na+ ions, [I-125] -2-iodo-D-tyrosine was taken up reversibly in the RIM cells, with an apparent accumulation, probably for the larger part by the LAT1 system. Dynamic planar imaging showed that the uptake in the tumors of [(123)]-2-iodo-D-tyrosine was somewhat lower than that of [I-123]-2-iodo-L-tyrosine. At 30 min postinjection, the mean differential uptake ratio values of the L- and D-enantiomers are 2.5 0.7 and 1.7 0.6, respectively. Although the uptake of the D-isomer is lower, probably due to a faster clearance from the blood, the tumor-background ratio is the same as that of the L-analogue.Conclusion: A large part (75%) of [I-125]-2-iodo-D-tyrosine in vitro and [I-123]-2-iodo-D-tyrosine in vivo is reversibly highly taken up in RIM tumor cells by Na+-independent LAT transport systems, more likely by the LAT1 The clearance from the blood of [I-123]-2-iodo-D-tyrosine in the rats is faster than that of the L-analogue, resulting in a slightly lower tumor uptake but with the same tumor-background ratio. (c) 2006 Elsevier Inc. All rights reserved.