Kersemans Veerle, Cornelissen Bart, Kersemans Ken, Bauwens Matthias, Dierckx Rudi A, De Spiegeleer Bart, Mertens John, Slegers Guido
Laboratory for Radiopharmacy, Universiteit Gent, Harelbekestraat 72, B-9000, Gent, Belgium.
Eur J Nucl Med Mol Imaging. 2006 Aug;33(8):919-27. doi: 10.1007/s00259-005-0043-9. Epub 2006 Mar 30.
In vitro in the R1M cell model and in vivo in the R1M tumour-bearing athymic model, both [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: -phenylalanine have shown promising results as tumour diagnostic agents for SPECT. In order to compare these two amino acid analogues and to examine whether the observed characteristics could be generalised, both isomers were evaluated in various tumour models.
Transport type characterisation in vitro in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M cells with [(123)I]-2-iodo-L: -phenylalanine was performed using the method described by Shotwell et al. Subsequently, [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: -phenylalanine tumour uptake and biodistribution were evaluated using dynamic planar imaging and/or dissection in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M inoculated athymic mice. Two-compartment blood modelling of the imaging results was performed.
In vitro testing demonstrated that [(123)I]-2-iodo-L: -phenylalanine was transported in all tumour cell lines by LAT1. In all tumour models, the two amino acid analogues showed the same general biodistribution characteristics: high and specific tumour uptake and renal tracer clearance. Two-compartment modelling revealed that the D: -isomer showed a faster blood clearance together with a faster distribution to the peripheral compartment in comparison with [(123)I]-2-iodo-L: -phenylalanine.
[(123)I]-2-iodo-L: -phenylalanine and its D: -isomer are promising tumour diagnostic agents for dynamic planar imaging. They showed a high and similar uptake in all tested tumours. [(123)I]-2-iodo-D: -phenylalanine showed better tracer characteristics concerning radiation dose to other organs.
在R1M细胞模型中进行体外实验，以及在R1M荷瘤裸鼠模型中进行体内实验，[（123）I]-2-碘-L-苯丙氨酸和[（123）I]-2-碘-D-苯丙氨酸作为肿瘤诊断剂用于单光子发射计算机断层显像（SPECT）均已显示出有前景的结果。为了比较这两种氨基酸类似物，并检验所观察到的特性是否具有普遍性，在各种肿瘤模型中对这两种异构体进行了评估。
采用Shotwell等人描述的方法，在A549、A2058、C6、C32、Capan2、EF43fgf4、HT29和R1M细胞中对[（123）I]-2-碘-L-苯丙氨酸进行体外转运类型表征。随后，通过动态平面显像和/或解剖，在接种了A549、A2058、C6、C32、Capan2、EF43fgf4、HT29和R1M的裸鼠中评估[（123）I]-2-碘-L-苯丙氨酸和[（123）I]-2-碘-D-苯丙氨酸的肿瘤摄取和生物分布。对显像结果进行二室血液建模。
体外试验表明，[（123）I]-2-碘-L-苯丙氨酸在所有肿瘤细胞系中均通过LAT1转运。在所有肿瘤模型中，这两种氨基酸类似物均表现出相同的总体生物分布特征：肿瘤摄取高且具有特异性，以及示踪剂经肾脏清除。二室建模显示，与[（123）I]-2-碘-L-苯丙氨酸相比，D-异构体的血液清除更快，且向周边室的分布也更快。
[（123）I]-2-碘-L-苯丙氨酸及其D-异构体是用于动态平面显像的有前景的肿瘤诊断剂。它们在所有测试肿瘤中均表现出高且相似的摄取。[（123）I]-2-碘-D-苯丙氨酸在对其他器官的辐射剂量方面显示出更好的示踪剂特性。
