Körner Meike, Waser Beatrice, Strobel Oliver, Büchler Markus, Reubi Jean Claude
Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, PO Box 62, Murtenstrasse 31, CH-3010 Berne, Switzerland.
Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
EJNMMI Res. 2015 Mar 24;5:17. doi: 10.1186/s13550-015-0094-2. eCollection 2015.
The frequent expression of neurotensin receptors (NT-R) in primaries of pancreatic ductal carcinomas has triggered the development of radioactive neurotensin analogs for possible in vivo targeting of these tumors. However, the complete lack of information regarding NT-R in liver metastases of pancreatic cancer and pancreatic intraepithelial neoplasia (PanIN) makes an in vitro study of NT-R in these tissues indispensable.
Using in vitro receptor autoradiography with (125)I-[Tyr(3)]-neurotensin, NT-R were investigated in 18 primaries and 23 liver metastases of pancreatic ductal carcinomas as well as in 19 PanIN lesions.
We report here that 13 of 18 ductal carcinoma primaries and 14 of 23 liver metastases expressed NT-R. Moreover, none of the six PanIN 1B cases expressed NT-R, while two of six PanIN 2 and five of seven PanIN 3 expressed NT-R. Binding was fully displaced by the type 1 NT-R-selective antagonist SR48692, indicating that the NT-R in the tumors are of the type 1 NT-R subtype.
These in vitro data extend the currently available information on NT-R in invasive and non-invasive pancreatic ductal tumors. They suggest that type 1 NT-R may be a novel, specific marker of PanIN of higher degree. The high expression of NT-R in primaries and metastases of invasive cancer strongly support the need to develop radioactive neurotensin analogs for the diagnosis and therapy of this tumor type.
神经降压素受体(NT-R)在胰腺导管癌原发灶中频繁表达,这促使了放射性神经降压素类似物的研发,以便在体内对这些肿瘤进行可能的靶向治疗。然而,关于胰腺癌肝转移灶和胰腺上皮内瘤变(PanIN)中NT-R的信息完全缺失,使得对这些组织中的NT-R进行体外研究变得不可或缺。
使用(125)I-[酪氨酸(3)]-神经降压素进行体外受体放射自显影,对18例胰腺导管癌原发灶、23例肝转移灶以及19例PanIN病变中的NT-R进行研究。
我们在此报告,18例导管癌原发灶中有13例以及23例肝转移灶中有14例表达NT-R。此外,6例PanIN 1B病例均未表达NT-R,而6例PanIN 2中有2例以及7例PanIN 3中有5例表达NT-R。结合被1型NT-R选择性拮抗剂SR48692完全取代,表明肿瘤中的NT-R为1型NT-R亚型。
这些体外数据扩展了目前关于侵袭性和非侵袭性胰腺导管肿瘤中NT-R的可用信息。它们表明1型NT-R可能是高度PanIN的一种新型特异性标志物。NT-R在侵袭性癌的原发灶和转移灶中的高表达强烈支持开发放射性神经降压素类似物用于这种肿瘤类型的诊断和治疗的必要性。