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. 1998 Apr;42(4):546-50.
doi: 10.1136/gut.42.4.546.

Neurotensin receptors: a new marker for human ductal pancreatic adenocarcinoma

Affiliations

Neurotensin receptors: a new marker for human ductal pancreatic adenocarcinoma

J C Reubi et al. Gut. 1998 Apr.

Abstract

Background/aims: New imaging possibilities for early diagnosis of the devastating exocrine pancreatic adenocarcinomas would be highly welcome. Recently, pancreatic neuroendocrine tumours have been successfully visualised in vivo on the basis of their high density of receptors for the regulatory peptide somatostatin. Unfortunately, exocrine pancreatic tumours do not express sufficient amounts of somatostatin receptors. Therefore over-expression of other regulatory peptide receptors in these tumours needs to be found.

Methods: Receptors for the regulatory peptide neurotensin were evaluated in vitro by receptor autoradiography in 24 ductal pancreatic adenocarcinomas, 20 endocrine pancreatic cancers, 18 cases of chronic pancreatitis, and 10 normal pancreatic glands.

Results: Some 75% of all ductal pancreatic adenocarcinomas, most of them differentiated, were neurotensin receptor positive, whereas endocrine pancreatic cancers did not express neurotensin receptors. No neurotensin receptors were found in chronic pancreatitis or normal pancreatic tissues, including pancreatic acini, ducts, and islets.

Conclusions: The selective and high expression of neurotensin receptors in ductal pancreatic adenocarcinomas could form the molecular basis for potential clinical applications, such as in vivo neurotensin receptor scintigraphy for early tumour diagnosis, radiotherapy with radiolabelled neurotensin analogues, and chemotherapy with neurotensin receptor antagonists.

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Figures

Figure 1
Figure 1
Density of neurotensin receptors in various human pancreatic tissues. A, ductal pancreatic adenocarcinomas (n = 24); 18 are differentiated tumours (grade I or II), and six are poorly differentiated tumours (grade II-III or III). B, endocrine pancreatic cancers (n = 20). C, chronic pancreatitis (n = 18). D, normal pancreas (n = 10). In A and B, the neurotensin receptor content of each tumour (dpm/mg tissue) was measured by quantitative in vitro receptor autoradiography.13 In C and D, the pancreatic acini, ducts, and islets were evaluated for their neurotensin receptor content by the same method.
Figure 2
Figure 2
Neurotensin receptors in two well differentiated ductal pancreatic adenocarcinomas. (A) and (B) show the haematoxylin-eosin stained sections representing tumour duct-like structures (arrowheads) surrounded by non-neoplastic pancreatic acini (asterisks). Bars = 1 mm. (C) and (D) show autoradiograms with total binding of 125I-[Tyr3]-neurotensin. The black areas (arrowheads) represent the neurotensin receptors in the tumour ducts. The asterisks indicate the receptor-free pancreatic acini. (E) and (F) show autoradiograms with non-specific binding of 125I-[Tyr3]-neurotensin (in the presence of 106 M neurotensin).
Figure 3
Figure 3
High affinity and specificity of the 125I-[Tyr3]-neurotensin binding in a displacement experiment. Sections of a ductal pancreatic adenocarcinoma were incubated with 125I-[Tyr3]-neurotensin and increasing concentrations of unlabelled neurotensin, acetyl-neurotensin-(8-13), and neurotensin-(1-11). High affinity displacement of the trace is found with neurotensin and acetyl-neurotensin-(8-13), whereas the biologically inactive neurotensin-(1-11) had no effect. Non-specific binding was subtracted from all values.
Figure 4
Figure 4
Absence of neurotensin receptors in normal human pancreatic tissue (A-C) and in chronic pancreatitis (D-F). (A), (D) Haematoxylin-eosin stained sections showing pancreatic acini (Ac), pancreatic ducts (arrowheads), and pancreatic islets (arrows). Bars = 1 mm. (B), (E) Autoradiograms showing total binding of 125I-[Tyr3]-neurotensin. (C), (F) Autoradiograms showing non-specific binding of 125I-[Tyr3]-neurotensin (in the presence of 106 M neurotensin).
Figure 5
Figure 5
Endocrine pancreatic tumour lacking neurotensin receptors (B) but expressing a high density of somatostatin receptors (C). (A) Haematoxylin-eosin stained section showing the tumour. Bar = 1 mm. (B) Autoradiogram showing total binding of 125I-[Tyr3]-neurotensin. (C) Autoradiogram showing sst2 somatostatin receptors identified by the binding of 125I-[Tyr3]-octreotide (OCT-R). In (B) and (C), non-specific binding was negligible.

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