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Background: Peptide-based agents are used in molecular imaging due to their unique properties, such as rapid clearance from the circulation, high affinity and target selectivity. Many of the radiolabeled peptides have been clinically experienced with diagnostic accuracy. The aim of this study was to investigate in vivo biological behavior of [ 99m Tc(CO) 3 (H 2 O) 3 ]+ radiolabeled glycylglycine (GlyGly)., Methods: Glycylglycine was radiolabeled with a high radiolabeling yield of 94.69±2%, and quality control of the radiolabeling process was performed by thin layer radiochromatography (TLRC) and High-Performance Liquid Radiochromatography (HPLRC). Lipophilicity study for radiolabeled complex ( 99m Tc(CO) 3 -Gly-Gly) was carried out using solvent extraction. The in vivo evaluation was performed by both biodistribution and SPECT imaging., Results: The high radiolabelling yield of 99m Tc(CO) 3 -GlyGly was obtained and verified by TLRC and HPLRC as well. According to the in vivo results, SPECT images and biodistribution data are in good accordance. The excretion route from the body was both hepatobiliary and renal., Conclusion: This study shows that 99m Tc(CO) 3 -GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, 99m Tc(CO) 3 -GlyGly can be performed on tumor-bearing animals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The intestinal oligopeptide transporter (PepT1) is responsible for the absorption of nutrient di-tripeptide and mediates the transportation of bacterial product N-formylmethionylleucyl-phenylalanine (fMLP) that induces intestinal inflammation. PepT1 is absent from normal colon epithelia but is abnormally expressed in the colon of patients with inflammatory bowel diseases. This study was designed to investigate the role of PepT1 in colonic inflammation and its relation with fMLP., Materials and Methods: PepT1 mRNA expression was analyzed by RT-PCR and oligopeptide transportation was quantified by the luminal perfusion with cephalexin in rats following 80% small bowel resection. The inflammatory effects of PepT1-mediated fMLP transport were also investigated by the measurement of myeloperoxidase (MPO) activity, histological analysis, and the use of Gly-Gly (Glycine-Glycine, a competitive PepT1 blocker)., Results: The overexpression of PepT1 was observed, peaking at 2 weeks post-operation, with its levels declining to 12% at week 4. The ability of oligopeptide transport was correlated with the PepT1 levels. The fMLP perfusion into the colon of rats with bowel resection resulted in an increased MPO activity and mucosal inflammation at week 2, but not at week 4 post-operation. The administration of Gly-Gly (50 mm) competitively inhibited PepT1, reducing the fMLP-associated MPO activation and colonic mucosal damage., Conclusions: The colonic PepT1 overexpression induced by bowel resection increases the transport of bacterial product fMLP and hence causes colonic inflammation, which may serve as a previously unrecognized pathway resulting in colon mucosa damage.

Kinetics of glycylglycine hydrolysis and absorption as well as that of free glycine absorption in isolated loop of the small intestine was studied in chronic experiments in two groups of rats. In the 1st group (n = 5), the isolated loop daily received for 1 or two hours a glucose load (25 mM), whereas in the 2nd group (n = 4)--a glutamic acid load (25 mM). The "true" values (i.e. corrected for the influence of the pre-epithelial layer) of the Michaelis constant for dipeptide transport were lower than those for the free glycine transport: 16 +/- 1.8 versus 36.3 +/- 3.7 mM (in the 1st group) and 15.9 +/- 2.2 versus 34.0 +/- 3.7 mM (in the 2nd group), whereas values of the maximal rate of active transport as calculated per 1 cm of the intestine length were, on the contrary, higher: 0.64 +/- 0.06 versus 0.42 +/- 0.10 mumol/(min.cm) 1st group and 0.86 +/- 0.13 versus 0.56 +/- 0.04 mumol/(min.cm) in the in the 2nd group. It has been shown that, under these conditions, regarded as the most physiological, over 90% of glycylglycine is absorbed via the peptide transport system. Only a small part of this dipeptide amount (less than 10%) splits during membrane hydrolysis with subsequent absorption of the derived glycine. It has also been found that glutamic acid solution as a regular substrate load is more effective (as compared with the glucose solution) in retarding the atrophic changes occurring in the isolated intestine loop and in preserving its structural and functional parameters on a higher level.

Objective: The aim of the study was to investigate net ultrafiltration (NUF) with a new bicarbonate glycylglycine (BiGG) peritoneal dialysis solution compared to the standard lactate (La) solution., Design: In six groups of 12 normal rabbits each we measured NUF after a 2-, 4-, and 6-hour peritoneal dialysis with a BiGG solution (pH 7.35) and a standard La solution (pH 5.5) of similar glucose, electrolyte, and osmolality formulation. Furthermore, we studied the phosphatidylcholine concentration in the effluent of the two solutions., Results: NUF volume was significantly greater with the BiGG rather than with the La solution by approximately 15% (p < 0.05), 30% (p < 0.01), and 40% (p < 0.005) at 2, 4, and 6 hours, respectively. The glucose absorption rate was greater with the La solution than with the BiGG solution, but the difference was significant only at 2 hours (p < 0.05). pH was increased in the La solution from its initial value of 5.5 to 7.18, 7.32, and 7.40 at 2, 4 and 6 hours, respectively, while it remained almost unchanged in the BiGG solution. Phosphatidylcholine (PC) in the peritoneal effluent was significantly higher in the BiGG solution in all instances (p < 0.0001)., Conclusion: It is concluded that the BiGG solution, which has a stable pH, 7.35, due to the potent buffering capacity of bicarbonate and glycylglycine, enhances peritoneal NUF by maintaining a higher osmotic gradient and retarding lymphatic absorption through an increase in PC concentration in the peritoneal cavity.