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神经内分泌肿瘤中生长抑素受体亚型2对111铟标记的奥曲肽的结合

111In-labelled octreotide binding by the somatostatin receptor subtype 2 in neuroendocrine tumours.

作者信息

Hashemi S H, Benjegård S-A, Ahlman H, Wängberg B, Forssell-Aronsson E, Billig H, Nilsson O

机构信息

Lundberg Laboratory for Cancer Research at the Department of Pathology, Göteborg University, Göteborg, Sweden.

出版信息

Br J Surg. 2003 May;90(5):549-54. doi: 10.1002/bjs.4069.

DOI:10.1002/bjs.4069
PMID:12734860
Abstract

BACKGROUND

The aim of this study was to investigate the importance of somatostatin receptor subtype 2 (SSTR2) expression for 111In-labelled diethylenetriamine-pentaacetic acid (DTPA)-D-Phe1-octreotide binding and uptake of 111In in neuroendocrine tumours.

METHODS

111In activity concentrations in surgical biopsies from neuroendocrine tumours (midgut carcinoid and medullary thyroid carcinoma), breast carcinoma and blood were determined 1-8 days after intravenous injection of 111In-labelled DTPA-D-Phe1-octreotide (140-350 MBq). The ratio of 111In activity concentrations between tumour tissue and blood (T/B value) was calculated. The expression of SSTR2 messenger RNA (mRNA) in tumour biopsies was quantitated by ribonuclease protection assay and SSTR2 protein was localized by immunocytochemistry.

RESULTS

T/B values were highest for tumour biopsies from midgut carcinoids (mean 160 (range 4-1200); n = 65) followed by medullary thyroid carcinoma (mean 38 (range 2-350); n = 88) and breast carcinoma (mean 18 (range 4-41); n = 4). The expression of SSTR2 mRNA (relative to the NCI-H69 cell line) was highest in tumour biopsies from midgut carcinoids (mean 2.5 (range 0.83-6.0); n = 40) followed by medullary thyroid carcinoma (mean 1.3 (range 0.20-6.0); n = 7) and breast carcinoma (mean 0.66 (range 0.29-1.0); n = 9). In tumour biopsies SSTR2 protein was localized exclusively to tumour cells.

CONCLUSION

Midgut carcinoid tumours showed a much higher level of SSTR2 expression than medullary thyroid carcinoma in accordance with superior tumour imaging by octreotide scintigraphy. The high SSTR2 mRNA values and T/B values observed in midgut carcinoid tumours were positively correlated.

摘要

背景

本研究旨在探讨生长抑素受体2型(SSTR2)表达对于神经内分泌肿瘤中铟-111标记的二乙烯三胺五乙酸(DTPA)-D-苯丙氨酸-1-奥曲肽结合及铟-111摄取的重要性。

方法

静脉注射铟-111标记的DTPA-D-苯丙氨酸-1-奥曲肽(140 - 350 MBq)后1 - 8天,测定神经内分泌肿瘤(中肠类癌和甲状腺髓样癌)、乳腺癌手术活检组织及血液中的铟-111活度浓度。计算肿瘤组织与血液中铟-111活度浓度之比(T/B值)。通过核糖核酸酶保护试验对肿瘤活检组织中SSTR2信使核糖核酸(mRNA)的表达进行定量,并用免疫细胞化学法对SSTR2蛋白进行定位。

结果

中肠类癌肿瘤活检组织的T/B值最高(平均160(范围4 - 1200);n = 65),其次是甲状腺髓样癌(平均38(范围2 - 350);n = 88)和乳腺癌(平均18(范围4 - 41);n = 4)。中肠类癌肿瘤活检组织中SSTR2 mRNA的表达(相对于NCI - H69细胞系)最高(平均2.5(范围0.83 - 6.0);n = 40),其次是甲状腺髓样癌(平均1.3(范围0.20 - 6.0);n = 7)和乳腺癌(平均0.66(范围0.29 - 1.0);n = 9)。在肿瘤活检组织中,SSTR2蛋白仅定位于肿瘤细胞。

结论

与甲状腺髓样癌相比,中肠类癌肿瘤显示出更高水平的SSTR2表达,这与奥曲肽闪烁扫描对肿瘤的更好成像结果一致。中肠类癌肿瘤中观察到的高SSTR2 mRNA值与T/B值呈正相关。

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