Bauwens Matthias, Lahoutte Tony, Kersemans Ken, Gallez Carol, Bossuyt Axel, Mertens John
Radiopharmaceutical Chemistry, BEFY, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
Nucl Med Biol. 2006 Aug;33(6):735-41. doi: 10.1016/j.nucmedbio.2006.05.004. Epub 2006 Jul 18.
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 [(123)I]-2-iodo-L-tyrosine, a tracer recently introduced by our group into clinical trials. The uptake of 2-amino-3-(4-hydroxy-2-[(123/125)I]iodophenyl)-D-propanoic acid (2-iodo-D-tyrosine) was studied in vitro in LAT1-expressing R1M rat rhabdomyosarcoma cells and in vivo in R1M tumor-bearing Wag/Rij rats.
The uptake of [(125)I]-2-iodo-L-tyrosine and [(125)I]-2-iodo-D-tyrosine into R1M cells was determined in appropriate buffers, allowing the study of the involved transport systems. In vivo, the biodistribution in R1M-bearing rats of [(123)I]-2-iodo-L-tyrosine and [(123)I]-2-iodo-D-tyrosine was performed by both dynamic and static planar imaging with a gamma camera.
In in vitro conditions, the uptake of both [(125)I]-2-iodo-L-tyrosine and [(125)I]-2-iodo-D-tyrosine in the HEPES buffer was 25% higher in the presence of Na(+) ions. In the absence of Na(+) ions, [(125)I]-2-iodo-D-tyrosine was taken up reversibly in the R1M 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)I]-2-iodo-D-tyrosine was somewhat lower than that of [(123)I]-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.
A large part (75%) of [(125)I]-2-iodo-D-tyrosine in vitro and [(123)I]-2-iodo-D-tyrosine in vivo is reversibly highly taken up in R1M tumor cells by Na(+)-independent LAT transport systems, more likely by the LAT1. The clearance from the blood of [(123)I]-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.
最近，有关D-氨基酸在肿瘤体内摄取的研究取得了令人鼓舞的成果。因此，我们决定评估[(123)I]-2-碘-L-酪氨酸的D-类似物在肿瘤中的摄取情况，该示踪剂最近由我们团队引入临床试验。研究了2-氨基-3-(4-羟基-2-[(123/125)I]碘苯基)-D-丙酸（2-碘-D-酪氨酸）在体外LAT1表达的R1M大鼠横纹肌肉瘤细胞中的摄取情况以及在体内R1M荷瘤Wag/Rij大鼠中的摄取情况。
在适当的缓冲液中测定[(125)I]-2-碘-L-酪氨酸和[(125)I]-2-碘-D-酪氨酸进入R1M细胞的摄取情况，以便研究相关的转运系统。在体内，通过γ相机进行动态和静态平面成像，测定[(123)I]-2-碘-L-酪氨酸和[(123)I]-2-碘-D-酪氨酸在R1M荷瘤大鼠中的生物分布。
在体外条件下，在HEPES缓冲液中，当存在Na(+)离子时，[(125)I]-2-碘-L-酪氨酸和[(125)I]-2-碘-D-酪氨酸的摄取量均高出25%。在不存在Na(+)离子的情况下，[(125)I]-2-碘-D-酪氨酸在R1M细胞中被可逆摄取，出现明显蓄积，可能大部分是通过LAT1系统。动态平面成像显示，[(123)I]-2-碘-D-酪氨酸在肿瘤中的摄取略低于[(123)I]-2-碘-L-酪氨酸。注射后30分钟，L-和D-对映体的平均差异摄取比值分别为2.5±0.7和1.7±0.6。尽管D-异构体的摄取较低，可能是由于其从血液中清除较快，但肿瘤与背景的比值与L-类似物相同。
体外[(125)I]-2-碘-D-酪氨酸和体内[(123)I]-2-碘-D-酪氨酸的很大一部分（75%）通过不依赖Na(+)的LAT转运系统在R1M肿瘤细胞中被可逆性高度摄取，更可能是通过LAT1。大鼠体内[(123)I]-2-碘-D-酪氨酸从血液中的清除比L-类似物快，导致肿瘤摄取略低，但肿瘤与背景的比值相同。
