Deehan B, Carnochan P, Trivedi M, Tombs A
Department of Physics, Royal Cancer Hospital, Sutton, Surrey, UK.
Eur J Nucl Med. 1993 Feb;20(2):101-6. doi: 10.1007/BF00168868.
Radiolabelled amino acids combined with positron emission tomography (PET) show promise for the accurate delineation of viable tumour extent and may also provide a rapid and sensitive indicator of response to therapy. We have investigated the potential use of the radioiodinated amino acid analogue L-3-iodo-alpha-methyl tyrosine (IMT) for these purposes using experimental tumours in hooded rats. Preliminary studies using HSN tumours and IMT labelled with iodine-125 demonstrated maximum tumour uptake at 15 min post injection although an improved tumour-to-brain ratio was seen at 24 h due to the relatively poor retention of IMT in normal brain. Brain uptake of IMT was also found to be substantially reduced by competition with another large neutral amino acid phenylalanine; however, relatively less effect was seen in tumour, and in skeletal muscle no change in IMT uptake was observed. Quantitative autoradiography revealed no sign of heterogeneity in tumour IMT uptake: good penetration was seen even in poorly vascularised regions as confirmed by endothelial immunohistochemistry. Similar levels of IMT uptake were found in the OES.HR1 tumour during growth supplemented by exogenous oestrogen. Following arrest of tumour growth by removal of the oestrogen stimulus, IMT uptake was seen to fall from 1.7% to 1.0% of the injected dose per gram: this was matched by a fall in tumour blood flow as estimated by technetium-99m hexamethylpropylene amine oxime distribution. It appears that IMT uptake is more strongly influenced by blood flow than cell proliferation and that intratumoural distribution of IMT is principally determined by diffusion.
放射性标记氨基酸与正电子发射断层扫描（PET）相结合，有望准确描绘存活肿瘤范围，还可能为治疗反应提供快速且灵敏的指标。我们使用带帽大鼠的实验性肿瘤，研究了放射性碘化氨基酸类似物L-3-碘-α-甲基酪氨酸（IMT）用于这些目的的潜在用途。使用HSN肿瘤和用碘-125标记的IMT进行的初步研究表明，注射后15分钟肿瘤摄取量最大，不过由于IMT在正常脑组织中的滞留相对较差，在24小时时肿瘤与脑的比率有所改善。还发现与另一种大中性氨基酸苯丙氨酸竞争可大幅降低IMT在脑中的摄取；然而，在肿瘤中观察到的影响相对较小，并且在骨骼肌中未观察到IMT摄取的变化。定量放射自显影显示肿瘤IMT摄取没有异质性迹象：即使在内皮免疫组织化学证实的血管化不良区域也能看到良好的穿透。在补充外源性雌激素的生长过程中，OES.HR1肿瘤中发现了相似水平的IMT摄取。在通过去除雌激素刺激使肿瘤生长停止后，IMT摄取量从每克注射剂量的1.7%降至1.0%：这与用锝-99m六甲基丙烯胺肟分布估计的肿瘤血流量下降相匹配。看来IMT摄取受血流的影响比细胞增殖更强，并且IMT在肿瘤内的分布主要由扩散决定。
