Tissue distribution of octreotide binding receptors in normal mice and strains prone to autoimmunity.

Abstract

Somatostatin has diverse functions, including immunomodulatory functions. In humans, sites of active inflammation can be visualized by the administration of 111In-DTPA(0)-octreotide, a radiolabelled somatostatin analogue. We wished to establish an animal model for preclinical evaluation of the effects of somatostatin analogues on the immune system. However, most animal models for immunological diseases are murine. This report is a preliminary study of the distribution of somatostatin receptors in mouse tissues, with emphasis on the immune system. Tissue distribution of octreotide binding receptors in normal (BALB/c) mice was determined in vivo by receptor binding of 111In-DTPA(0)-octreotide and in vitro and ex vivo by receptor autoradiography. Additionally, we investigated the tissue distribution of octreotide binding receptors in inflammatory lesions in a murine model of immune mediated disease, i.e. pre-diabetic pancreatic infiltration in the non-obese diabetic mouse strain. High specific uptake of radioactivity was seen in the thymus (range 1-1.7% ID/g) and the pituitary (1-1.6% ID/g) in all mouse strains. Specific uptake was also found in the stomach (0.1-0.7% ID/g), in the adrenal glands (0.1-0.3% ID/g) and in the pancreas (0.1-0.3% ID/g). However, we did not detect increased uptake of radiolabelled octreotide in the pancreas of pre-diabetic NOD mice. Autoradiography on tissue sections confirmed the presence of octreotide binding sites in the tissues that showed specific uptake. Moreover, by using autoradiography we could localize the cortex of the thymus and the anterior part of the pituitary as the localization of specific and high affinity, octreotide binding sites. A high, but not a receptor mediated, uptake of radioactivity was seen in the kidneys and was significantly higher in females than in males (12-19% vs 4% ID/g, respectively). Our results point to profound species differences in the tissue distribution of octreotide binding receptors. Of particular interest is the high uptake of 111In-DTPA(0)-octreotide in the cortex of the mouse thymus. This offers perspectives for the use of this animal in studies concerning the effect of somatostatin analogues on the immune system. To our knowledge, this is the first report on the tissue distribution of octreotide binding receptors in mice.