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The renal handling of carboxyamidated gastrins, glycine-extended gastrins and NH2-terminal progastrin fragments has been investigated. Healthy subjects were subjected to intravenous administration of carboxyamidated gastrin-17, glycine-extended gastrin-17 and progastrin fragment to determine their respective urinary clearances. Results show that renal excretion of progastrin products is not significant compared with renal metabolism and that renal handling of the peptides is dependent on their molecular structure.

Elimination of amidated gastrin-17 and glycine-extended gastrin-17 were investigated as a measure of the arteriovenous difference of gastrin-17 during constant-rate infusion of the peptide in anesthetized pigs. Elimination were recorded in the hindlimb, kidney, head and the gut. Measurements of half-life, metabolic clearance rate and apparent volume of distribution for amidated gastrin-17 were different from those for glycine-extended gastrin-17. This suggests that extraction of these gastrins varies in different organs.

Gastrin-52, an alpha-carboxyamidated product of progastrin, increases gastric acid secretion in humans but is less effective than gastrin-17, a nonsulfated product. This is probably because gastrin-52 has a greater half-life and takes longer to establish an equilibrium between its concentration in the plasma and its receptors. The removal of gastrin-52 is biexponential while that of gastrin-17 is monoexponential. A small amount of gastrin-52 breaks down into smaller peptides in the plasma or blood capillaries.

Palnaes Hansen, C., F. Stadil, and J. F. Rehfeld. Metabolism and acid secretory effect of sulfated and nonsulfated gastrin-6 in humans. Am J Physiol Gastrointest Liver Physiol 279: G903-G909, 2000.--The antral hormone gastrin is synthesized by processing progastrin into different peptides that stimulate gastric secretion. The effect on acid secretion depends mainly on the metabolic clearance rate of the peptides, but some of them may differ in potency and maximum acid output at similar concentrations in plasma. Sulfated and nonsulfated gastrin-6 are the smallest circulating bioactive gastrins in humans. Their effect and metabolism have now been investigated in nine normal subjects and compared with nonsulfated gastrin-17, a main product of progastrin. Maximum acid output after stimulation with gastrin-17, sulfated gastrin-6, and nonsulfated gastrin-6 were 28.3 [+ or -] 2.0, 24.5 [+ or -] 2.0 (P [is less than] 0.02), and 19.3 [+ or -] 2.3 (P [is less than] 0.05) mmol [H.sup.+]/50 min, respectively, and the corresponding [EC.sub.50] values were 43 [+ or -] 6, 24 [+ or -] 2 (P [is less than] 0.01), and 25 [+ or -] 2 (not significant) pmol/l. The half-life of gastrin-17 was 5.3 [+ or -] 0.3 min, the metabolic clearance rate (MCR) was 16.5 [+ or -] 1.3 ml [multiplied by] [kg.sup.-1] [multiplied by][min.sup.-1], and the apparent volume of distribution ([V.sub.d]) was 124.3 [+ or -] 9.6 ml/kg. The half-lives of sulfated and nonsulfated gastrin-6 were 2.1 [+ or -] 0.3 and 1.9 [+ or -] 0.3 min, the MCRs were 42.8 [+ or -] 3.7 and 139.4 [+ or -] 9.6 ml [kg.sup.-1] [min.sup.-1] (P [is less than] 0.01), and the [V.sub.d] were 139.0 [+ or -] 30.5 and 392.0 [+ or -] 81.6 (P [is less than] 0.01) ml [kg.sup.-1]. All pharmacokinetic parameters differed significantly from gastrin-17 (P [is less than] 0.01). We conclude that gastrin 6 has a higher potency but a lower efficacy than gastrin-17. The efficacy of gastrin-6 is increased by tyrosine O-sulfation, which also enhances the protection against elimination. gastric acid; pharmacodynamics; pharmacokinetics

Purpose: To investigate the accuracy of dedicated pancreatic multidetector computed tomography (MDCT) in the diagnosis of neuroendocrine pancreaticoduodenal tumors (NPTs). Material and Methods: MDCT and other imaging studies in patients with suspected NPTs were identified. Thirty dedicated MDCT studies were done in 23 patients. Fourteen patients (16 operations) subsequently had surgery. Imaging reports were reviewed and findings compared with surgical findings and findings in other imaging studies. Results: Patients with surgery: 19 NPTs (16 extrapancreatic gastrinomas and 3 pancreatic NPTs) were identified at surgery. MDCT identified 16 and somatostatin receptor scintigraphy (SRS) 11 out of 19 tumors. Endoscopic ultrasound detected 11 out of 14 NPTs. Patients without surgery: In 4 out of 9 patients, no NPTs were identified at MDCT. Conclusion: Dedicated MDCT of the pancreas can identify many NPTs, including small duodenal and periduodenal tumors, and the detection rate is better than reported in the older literature on CT. [ABSTRACT FROM AUTHOR]

Introduction: Liver metastases (LM) are frequent in patients with neuroendocrine tumors (NETs) and are associated with decreased overall survival (OS). Several treatment options are available depending on degree, localization, size and number of LM. For optimal choice of treatment and correct staging, accurate imaging modalities are crucial. Aim(s): To assess and compare several different imaging options available for patients with NETs and to evaluate if presence of LM was associated with decreased OS. Materials and methods: Ninety-two prospectively enrolled patients with histologically verified NETs underwent 111In-DTPAOctreotide scintigraphy (SRS), 123I-Metaiodobenzylguanidine(M IBG) scintigraphy, 18F-Fluorodeoxyglucose-PET(FDG-PET) and computer tomography(CT). OS based on presence of LM was estimated by the Kaplan-Meier method. Mean follow-up time from FDG-PET was 31 months. Results: Ninety-two patients were enrolled and imaged by SRS, MIBG, FDG and CT. SRS was positive in 52 patients (56%). MIBG was positive in 37 patients (39%). FDG was positive in 27 patients (29%). CT was positive in 61 patients (66%). Sixty-six patients (72%) had liver-positive loci on at least one scan. Patients with FDG-PET positive LM had significantly poorer OS than FDG-PET negative patients with a hazard ration of 3.7 (95% CI:1.9-7.2, p<0.001). Conclusion: The sensitivity of CT seems to be superior to the radionuclide-based methods for detection of LM. FDG-PET identified the least LM. However, the only prognostic imaging modality was FDG-PET where detection of LM was associated with decreased OS. [ABSTRACT FROM AUTHOR]

Introduction: Today, grading, and thereby choice of treatment strategy for patients with neuroendocrine (NE) tumors, is mainly based on the proliferation index, Ki-67. As a supplement to this pathological evaluation, a whole body image analysis could be of value. Aim(s): To investigate the prognostic value of FDG-PET in patients with WHO grade I and IINE tumors. Materials and methods: Eighty-one prospectively enrolled patients with NE tumors grade I and II underwent FDG-PET imaging. The prognostic value of the FDG-PET scan was evaluated. There were 47 grade I tumors (Ki-67 index2<20). Follow-up time after the FDG-PET scan was 31 ± 12.6 months (mean + SD). Results: FDG-PET identified pathological loci in 42 of 81 patients, giving an overall modest sensitivity of 52%. During the 3-year follow-up, 22 of the 81 patients died, and of these 22 events, 19 were FDG-PET positive and three were FDG-PET negative. Thus, in the FDG-positive group, 45% died, compared to 7.7% of the FDG-negative. A positive FDG-PET scan was associated with a significantly higher risk of death (p<0.001), with an HR of 7.3 (95% confidence interval: 2.1 - 24.6) in these low-grade NE tumors. Conclusion: FDG-PET predicts survival of grade I and IINE tumors. We therefore propose that FDG-PET can be a valuable prognostic tool even in NE tumors classified as low-grade. [ABSTRACT FROM AUTHOR]