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68Ga-DOTA-Tyr3-octreotate 肿瘤摄取:CA20948 大鼠模型中肿瘤血流的动物 PET 研究和急性生长抑素受体调节。

Tumor uptake of 68Ga-DOTA-Tyr3-octreotate: animal PET studies of tumor flow and acute somatostatin receptor modulation in the CA20948 rat model.

机构信息

Molecular Imaging and Experimental Radiotherapy Unit (MIER), Université Catholique de Louvain, B-1200 Brussels, Belgium.

出版信息

Nucl Med Biol. 2010 Feb;37(2):157-65. doi: 10.1016/j.nucmedbio.2009.09.006. Epub 2009 Nov 7.

DOI:10.1016/j.nucmedbio.2009.09.006
PMID:20152715
Abstract

INTRODUCTION

Factors determining the in vivo uptake of radiolabeled somatostatin analogs by neuroendocrine tumors are poorly known. The aim is to evaluate in vivo tumor perfusion and regulation of somatostatin receptors (sstr) following acute exposure to octreotide, in an animal model of neuroendocrine tumor.

METHODS

H(2)(15)O flow studies were performed in 8 CA20948 tumor-bearing rats and another 36 rats underwent three [(68)Ga]-DOTA-Tyr(3)-octreotate imaging sessions at 24-h intervals. After baseline (Day 0) imaging, scanning was repeated on Day 1 after octreotide injection (175 microg/kg), with a variable delay: no injection (controls, n=7), coinjection (n=6), and octreotide injection 20 min (n=7), 2 h (n=8) and 4 h (n=8) before imaging. Repeat images without octreotide was performed at Day 2 followed by sacrifice and tumor counting.

RESULTS

H(2)(15)O studies failed to measure quantitative tumor perfusion in this model. On Day 1, ratio of tumor uptake to Day 0 was 1.2+/-0.3 in controls; 0.6+/-0.2 in the coinjection group; 0.9+/-0.2, 1.1+/-0.1 and 1.2+/-0.2 in the other groups, respectively. Uptake in the coinjection group showed a statistically significant reduction of tumor uptake (P<.0001). All groups showed increased uptake on Day 2, without statistical differences between groups. In vivo tumor counts showed good correlation with ex vivo countings (R(2)=0.946).

CONCLUSION

Acute exposure to unlabeled octreotide in this neuroendocrine tumor model results in a rapid recycling or resynthesis of sstr. Positron emission tomography (PET) allowed to reliably assess quantitative uptake of [(68)Ga]-DOTA-Tyr(3)-octreotate over time in the same animal, but failed in this model to measure tumor perfusion.

摘要

简介

确定放射性标记生长抑素类似物在神经内分泌肿瘤体内摄取的因素知之甚少。本研究旨在评估在神经内分泌肿瘤动物模型中,奥曲肽急性暴露后体内肿瘤灌注和生长抑素受体(sstr)调节情况。

方法

在 8 只 CA20948 荷瘤大鼠中进行 H(2)(15)O 流量研究,另外 36 只大鼠在 24 小时的间隔内进行三次[(68)Ga]-DOTA-Tyr(3)-奥曲肽成像。在基线(第 0 天)成像后,在奥曲肽注射后第 1 天(175μg/kg)重复扫描,延迟时间不同:无注射(对照组,n=7)、共注射(n=6)、奥曲肽注射后 20 分钟(n=7)、2 小时(n=8)和 4 小时(n=8)前进行扫描。在第 2 天没有奥曲肽的情况下重复图像,然后进行肿瘤计数和处死。

结果

H(2)(15)O 研究未能在该模型中测量定量肿瘤灌注。在第 1 天,对照组肿瘤摄取与第 0 天相比为 1.2+/-0.3;共注射组为 0.6+/-0.2;其他组分别为 0.9+/-0.2、1.1+/-0.1 和 1.2+/-0.2。共注射组的摄取明显降低(P<.0001)。所有组在第 2 天的摄取均增加,但组间无统计学差异。体内肿瘤计数与体外计数具有良好的相关性(R(2)=0.946)。

结论

在该神经内分泌肿瘤模型中,奥曲肽的急性暴露导致 sstr 的快速再循环或重新合成。正电子发射断层扫描(PET)能够可靠地评估同一动物体内[(68)Ga]-DOTA-Tyr(3)-奥曲肽随时间的定量摄取,但在该模型中未能测量肿瘤灌注。

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