The Synthesis and Preclinical Investigation of Lactosamine-Based Radiopharmaceuticals for the Detection of Galectin-3-Expressing Melanoma Cells.

Given that galectin-3 (Gal-3) is a ß-galactoside-binding lectin promoting tumor growth and metastatis, it could be a valuable target for the treatment of Gal-3-expressing neoplasms. An aromatic group introduced to the C-3' position of lactosamine increased its affinity for Gal-3. Herein, we aimed at developing a radiopharmaceutical for the detection of Gal-3 positive malignancies. To enhance tumor specificity, a heterodimeric radiotracer capable of binding to both Gal-3 and αvß3 integrin was also synthetized. Arginine-glycine-asparagine (RGD) peptide is the ligand of angiogenesis- and metastasis-associated αvß3 integrin. Following the synthesis of the chelator-conjugated (2-naphthyl)methylated lactosamine, the obtained compound was applied as a precursor for radiolabeling and was conjugated to the RGD peptide by click reaction as well. Both synthetized precursors were radiolabeled with 68Ga, resulting in high labeling yield (>97). The biological studies were carried out using B16F10 melanoma tumor-bearing C57BL6 mice. High tumor accumulation of both labeled lactosamine derivatives­detected by in vivo PET and ex vivo biodistribution studies­indicated their potential for melanoma detection. However, the heterodimer radiotracer showed high hepatic uptake, while low liver accumulation characterized chelator-conjugated lactosamine, resulting in PET images with excellent contrast. Therefore, this novel carbohydrate-based radiotracer is suitable for the highly selective determination of Gal-3-expressing melanoma cells.

Synthesis of 68Ga-Labeled cNGR-Based Glycopeptides and In Vivo Evaluation by PET Imaging.

Tumor hypoxia induces angiogenesis, which is required for tumor cell survival. The aminopeptidase N receptor (APN/CD13) is an excellent marker of angiogenesis since it is overexpressed in angiogenic blood vessels and in tumor cells. Asparagine-glycine-arginine (NGR) peptide analogs bind selectively to the APN/CD13 recepto, therefore, they are important vector molecules in the development of a PET radiotracer which is capable of detecting APN-rich tumors. To investigate the effect of glycosylation and pegylation on in-vivo efficacy of an NGR-based radiotracer, two 68Ga-labeled radioglycopeptides were synthesized. A lactosamine derivative was applied to glycosylation of the NGR derivative and PEG4 moiety was used for pegylation. The receptor targeting potential and biodistribution of the radiopeptides were evaluated with in vivo PET imaging studies and ex vivo tissue distribution studies using B16-F10 melanoma tumor-bearing mice. According to these studies, all synthesized radiopeptides were capable of detecting APN expression in B16-F10 melanoma tumor. In addition, lower hepatic uptake, higher tumor-to background (T/M) ratio and prolonged circulation time were observed for the novel [68Ga]-10 radiotracer due to pegylation and glycosylation, resulting in more contrasting PET imaging. These in vivo PET imaging results correlated well with the ex vivo tissue distribution data.

Effect of Marine Algae Supplementation on Somatic Cell Count, Prevalence of Udder Pathogens, and Fatty Acid Profile of Dairy Goats' Milk.

The aim of this study was to evaluate the effect of the Schizochytrium limacinum marine algae on the milk composition and fatty acid profile, somatic cell count, and prevalence of pathogen bacteria in the raw milk of multiparous Alpine goats. Twenty-eight dairy goats were randomly allocated to two groups: control group (C)-fed with 1500 g alfalfa hay and 600 g concentrate; experimental group (MA)-received the same forages and concentrate supplemented with 10 g/head/day marine algae. The goats were housed indoors, while the experiment lasted five weeks, and the milk samples were taken every week. Marine algae feeding had no negative effect on milk composition. The marine algae inclusion significantly decreased the milk somatic cell count and the presence of udder pathogens in the MA group. Mean somatic cell count and presence of udder pathogens were 5.73 log cells/mL and 31%, respectively, in the C group, while these values were 5.34 log cells/mL and 10%, respectively, in the MA group. The marine algae supplementation significantly increased DHA and rumenic acid concentration in the milk of the MA group (0.32 and 0.99 g/100 g of fatty acids, respectively) compared to the C group (0.04 and 0.65 g/100 g of fatty acids, respectively). It can be concluded that a diet supplemented with marine algae significantly improves the udder health of goats and the concentrations of health-promoting fatty acids in milk.