ABSTRACT
This work analysed the influence of the chelating group and radioligand on somatostatin analogues in vivo and in vitro properties. The presence of DOTA in the radioiodinated peptide produced a labeled analogue with similar blood kinetics and biodistribution to (177)Lu-DOTATATE and with lower abdominal uptake than (131)I-TATE. In addition, (131)I-DOTATATE showed significative tumour uptake, despite not so persistent after 24h. (131)I-DOTATATE can represent a cost-effective alternative to lutetium labeled peptide for neuroendocrine tumours therapy.
Subject(s)
Iodine Radioisotopes , Lutetium , Neuroendocrine Tumors/diagnostic imaging , Radioisotopes , Somatostatin/analogs & derivatives , Animals , Chelating Agents , Heterocyclic Compounds, 1-Ring , Mice , Neuroendocrine Tumors/radiotherapy , Pharmacokinetics , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Somatostatin/pharmacokinetics , Tissue DistributionABSTRACT
In order to study the effect of undernutrition on the onset of disturbances in insulin secretion and insulin resistance, we compared the effects of a low protein diet containing 4% of protein (LPD) and a normal diet containing 25% of protein (NPD) supplied to the dams during the first 10 days of lactation when the pups turn into adults (90 days). We studies, in these rats, the insulin secretion, the glucose tolerance test (GTT) and, using the glucose clamp technique, the insulin resistance. The GTT showed a delay of the response of LPD group to the glucose challenge (1 mg/kg body weight) at 10 minutes (NPD = 450 +/- 27 mg/dl; LPD = 650 +/- 32 mg/dl, p < 0.01). The insulin secretion, four minutes after stimulation was found reduced in the LPD group (LPD = 1.1 +/- 0.08 microU/islet/min; NPD = 1.85 +/- 0.02 microU/islet/min, p < 0.01). Using the glucose clamp technique the plasma glucose concentration was raised during the first 20 minutes after the glucose stimulation with 10 mg/Kg-1.min-1 (NPD = 200 +/- 32 mg/dl and; LPD = 160 +/- 14 mg/dl., p < 0.01). Afterwards, the hyperglycemia was subsequently maintained (NPD = 154 +/- 9 mg/dl; LPD = 149 +/- 12 mg/dl) and the insulinemia was unchanged by infusion of glucose in the LPD group. In a similar experiment, the administration of glucose (10 mg/Kg-1. min-1) plus insulin (1.67 mU/Kg-1. min-1), the LPD group when compared with the NPD group, displayed an accentuated decreasing of glucose concentration level (LPD = 90 +/- 7 mg/dl; NPD = 130 +/- mg/dl., p < 0.01), 30 minutes after the infusion. The data suggest that undernutrition induces an adaptive process of insulin sensitivity which occurs together with an insulin secretion first phase blockage.
