Hashemi S H, Benjegård S-A, Ahlman H, Wängberg B, Forssell-Aronsson E, Billig H, Nilsson O
Lundberg Laboratory for Cancer Research at the Department of Pathology, Göteborg University, Göteborg, Sweden.
Br J Surg. 2003 May;90(5):549-54. doi: 10.1002/bjs.4069.
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.
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.
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.
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.
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。
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。
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。
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。