实验性大鼠肿瘤中放射性标记酪氨酸和碘甲基酪氨酸的摄取:对血流和肿瘤生长速度的影响。

P Carnochan, B Deehan, M Trivedi, A Tombs, J Sandle, R Ott
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摘要

放射标记氨基酸结合正电子发射断层扫描(PET)可能有助于描绘活肿瘤的范围,也可能提供对治疗反应的快速和敏感的指标。有希望的早期临床报告使我们研究了氨基酸类似物l -3-碘- α -甲基酪氨酸(IMT)的潜在用途,它可以用适合PET或传统单光子成像的同位素进行放射性碘化。我们研究了[125I]IMT在两种可移植肿瘤系统中的生物分布和动力学,并将结果与使用氚放射性标记的天然氨基酸l -酪氨酸(TYR)的结果进行了比较。在HSN和OES中发现相似水平的IMT和TYR摄取。HR1肿瘤在肿瘤生长期间。在OES被捕后。研究发现,雌激素消融、IMT和TYR摄取减少对HR1肿瘤生长的影响与肿瘤血流量下降密切相关。与IMT不同,肿瘤中TYR摄取的很大一部分被发现是蛋白质结合,即使在肿瘤生长停止后也是如此。定量放射自显影显示两种放射性示踪剂对肿瘤边界的清晰描绘。我们得出结论,IMT和TYR动力学受到血流和扩散的强烈影响,肿瘤生长状态可能与氨基酸摄取无关。
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Uptake of radiolabelled tyrosine and iodo-methyl tyrosine in experimental rat tumours: influence of blood flow and tumour growth rate.

Radiolabelled amino acids combined with Positron Emission Tomography (PET) may be useful for delineation of the extent of viable tumour and may also provide a rapid and sensitive indicator of response to therapy. Promising early clinical reports led us to investigate the potential use of the amino acid analogue L-3-iodo-alpha-methyl tyrosine (IMT), which may be radioiodinated with isotopes suitable for PET or conventional single photon imaging. We have studied the biodistribution and kinetics of [125I]IMT using two transplantable tumour systems in hooded rats, and have compared the findings with those using the natural amino acid L-tyrosine (TYR) radiolabelled with tritium. Similar levels of IMT and TYR uptake were found in HSN and OES.HR1 tumours during tumour growth. Following arrest of OES.HR1 tumour growth by oestrogen ablation, reduced IMT and TYR uptake was found to be closely matched by a fall in tumour blood flow. Unlike IMT, a substantial proportion of TYR uptake in tumours was found to be protein incorporated, even following tumour growth arrest. Quantitative autoradiography revealed sharp delineation of tumour boundary using either radiotracer. We conclude that IMT and TYR kinetics are strongly influenced by blood flow and diffusion, and that tumour growth status may not be closely associated with amino acid uptake.

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