Abstract
(English)
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Evaluation of a neurotensin analogue
After having established the chemical and biochemical characteristics as well as targeting properties of variousTc-99m labelled neurotensine analogues, one of these analogues, [99mTc(CO)3(H2O)3](NaHis)Ac-Lys-(YCH2-NH)-Arg-Pro-Tyr-Tle-Leu, in short 99mTc-NT-XI, was chosen for human imaging and biokinetic studies. A phase I/II study was initiated as soon as the approval of the Ethics Committee of the Faculty of Medicine of Lausanne and the Federal Authorities was obtained. Patients with carcinoma of the pancreas scheduled for surgery the day after the beginning of the study were included in order to measure plasma clearance, urinary elimination, whole body and organ distribution of the radioactive compound as well as tissue activity on the surgical specimens. Due to the particular design of the study that allowed us to obtain tissue fragments for uptake measurements we could obtain organ distribution data up to 4 hours after injection only. Plasma clearance was bi-exponential, with a mean T1/2 of 4 hours. About 40% of the activity was eliminated by the urines during the first 2 hours after injection, another 5% during the following 2 hours, from then on urinary activity was negligible. Concerning biodistribution we found uptake in organs known for being rich in neurotensine receptors, especially stomach and small intestine, but also in the pancreas, liver and spleen. As expected from the high urinary elimination, the highest activity was found in the kidneys. No uptake was found in other organs, especially brain and eyes. There was no thyroid uptake either, confirming the quality of labelling and stability of the compound. Concerning tissue samples, the tumours studied so far had not the expected high expression of neurotensine receptors or were constituted of very small isolated tumour elements. Uptake in the pancreas tumours was 0.002-0.005 % ID/g % (of injected dose per gram), comparable to the liver. In one patient uptake in the tumour involved duodenum was 0.005 % ID/g %. Tumour to blood ratios were favourable, between 3.1 and 7.7.
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