BACKGROUND: Somatostatin analogues labelled with radiometals or radiohalogens are useful for the imaging and treatment of somatostatin receptor-containing tumours. In this study, the procedures for the radioiodination of glucose-Tyr3-octreotate (gluc-Tyr3-tate) and radiolabelling of DOTA-Tyr3-octreotate (DOTA-Tyr3-tate) with 111In, 177Lu and 125I were compared and their metabolism in rats was analyzed. The usefulness of high performance liquid chromatography (HPLC) analysis and instant thin-layer chromatography on silica gel (ITLC-SG) for both radiochemical purity determination and analysis of metabolism in urine was investigated. MATERIALS AND METHODs: For labelling with radiometals, the formation of a complex with the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) functionality of the peptide was employed. Radioiodination was performed by the chloramime-T method. The radiochemical purity of radiolabelled peptides and the analyses of rat urine were determined by HPLC and/or ITLC-SG methods. Male Wistar rats were used in the elimination studies. RESULTS: DOTA-Tyr3-tate was simply radiolabelled with radiometals with high yield and high radiochemical purity. Stopping of the reaction was a critical step for radioiodination, therefore labelling of gluc-Tyr3-tate and DOTA-Tyr3-tate with 125I was not so simple and the reaction product had to be purified by preparative HPLC analysis. Whereas 111In-DOTA-Tyr3-tate and 177Lu-DOTA-Tyr3-tate were eliminated in rat urine in a practically unchanged form, a significant proportion of metabolites was observed with radioiodinated peptides, particularly at longer time intervals. CONCLUSION: Labelling of DOTA-Tyr3-tate with radiometals is simple and the radiochemical purity of prepared compounds is very high, while iodination of the peptides demands purification of the product by preparative HPLC. The analysis of rat urine showed that excretion of radioiodinated peptides included a significant proportion of metabolites.

• MeSH
• cyklické peptidy chemie   metabolismus   MeSH
• financování organizované MeSH
• glukosa analogy a deriváty   metabolismus   MeSH
• heterocyklické sloučeniny monocyklické chemie   metabolismus   MeSH
• izotopové značení MeSH
• krevní proteiny metabolismus   MeSH
• krysa rodu rattus MeSH
• lutecium chemie   MeSH
• potkani Wistar MeSH
• radiofarmaka chemická syntéza   metabolismus   MeSH
• radioizotopy india chemie   MeSH
• radioizotopy jodu chemie   MeSH
• radionuklidy chemie   MeSH
• vazba proteinů MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH

We have developed a simple system for the analysis of the affinity of anti-bromodeoxyuridine antibodies. The system is based on the anchored oligonucleotides containing 5-bromo-2'-deoxyuridine (BrdU) at three different positions. It allows a reliable estimation of the reactivity of particular clones of monoclonal anti-bromodeoxyuridine antibodies with BrdU in fixed and permeabilized cells. Using oligonucleotide probes and four different protocols for the detection of BrdU incorporated in cellular DNA, we identified two antibody clones that evinced sufficient reactivity to BrdU in all the tested protocols. One of these clones exhibited higher reactivity to 5-iodo-2'-deoxyuridine (IdU) than to BrdU. It allowed us to increase the sensitivity of the used protocols without a negative effect on the cell physiology as the cytotoxicity of IdU was comparable with BrdU and negligible when compared to 5-ethynyl-2'-deoxyuridine. The combination of IdU and the improved protocol for oxidative degradation of DNA provided a sensitive and reliable approach for the situations when the low degradation of DNA and high BrdU signal is a priority.

• MeSH
• bromodeoxyuridin metabolismus   MeSH
• buněčné klony MeSH
• DNA metabolismus   MeSH
• HCT116 buňky MeSH
• HeLa buňky MeSH
• idoxuridin analogy a deriváty   metabolismus   MeSH
• lidé MeSH
• monoklonální protilátky metabolismus   MeSH
• peptidové mapování * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This article provides a general overview of radiopharmaceuticals for diagnostics and therapy of neuroendocrine tumors. These agents employ specific differences between neuroendocrine tumors and normal tissues on the cellular level. Individual radiopharmaceuticals demonstrate examples of typical strategies for targeted radionuclide accumulation in tumor cells.

• MeSH
• 3-jodobenzylguanidin farmakologie   terapeutické užití   MeSH
• 5-hydroxytryptofan farmakologie   terapeutické užití   MeSH
• glukagonu podobný peptid 1 farmakologie   terapeutické užití   MeSH
• lidé MeSH
• neuroendokrinní nádory * farmakoterapie   radioterapie   MeSH
• radiofarmaka * farmakologie   terapeutické užití   MeSH
• somatostatin farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Horseradish peroxidase (HRP)/H2O2-mediated crosslinking of polypeptides in inverse miniemulsion is a promising approach for the development of next-generation biocompatible and biodegradable nanogels. Herein, we present a fundamental investigation of the effects of three surfactants and their different concentrations on the (HRP)/H2O2-mediated nanogelation of poly[N5-(2-hydroxyethyl)-l-glutamine-ran-N5-propargyl-l-glutamine-ran-N5-(6-aminohexyl)-l-glutamine]-ran-N5-[2-(4-hydroxyphenyl)ethyl)-l-glutamine] (PHEG-Tyr) in inverse miniemulsion. The surfactants sorbitan monooleate (SPAN 80), polyoxyethylenesorbitan trioleate (TWEEN 85), and dioctyl sulfosuccinate sodium salt (AOT) were selected and their influence on the nanogel size, size distribution, and morphology was evaluated. The most effective nanogelation stabilization was achieved with 20 wt% nonionic surfactant SPAN 80. The diameter of the hydrogel nanoparticles was 230 nm (dynamic light scattering, DLS) and was confirmed also by nanoparticle tracking analysis (NTA) which showed the diameters ranging from 200 to 300 nm. Microscopy and image analyses showed that the nanogel in the dry state was spherical in shape and had number-average diameter Dn = 26 nm and dispersity Р= 1.91. In the frozen-hydrated state, the nanogel appeared porous and was larger in size with Dn = 182 nm and Р= 1.52. Our results indicated that the nanogelation of the polymer precursor required a higher concentration of surfactant than classical inverse miniemulsion polymerization to ensure effective stabilization. The developed polypeptide nanogel was radiolabeled with 125I, and in vivo biodistribution and blood clearance evaluations were performed. We found that the 125I-labeled nanogel was well-biodistributed in the bloodstream, cleared from mouse blood during 48 h by renal and hepatic pathways and did not provoke any sign of toxic effects.

• MeSH
• myši MeSH
• nanogely MeSH
• peptidy MeSH
• peroxid vodíku * MeSH
• polyethylenglykoly MeSH
• polyethylenimin MeSH
• povrchově aktivní látky * MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Despite the rising trend of cancer disease incidence more and more patients succeed in their fight with the disease. Innovative drugs bring cures or at least improvements to the patient's quality of life. Extensive application of anticancer therapy however brings about the increase of adverse effects of the therapy. Toxic damage of the myocardium remains one of the severest organ damage types with life-threatening consequences. In the last decade, in addition to the known cardio toxicity of traditional cytostatics, specialists have more and more often been facing cardio toxicity caused by targeted oncology therapies. As myocardium damage is hard to treat when the stage of clinical symptoms is reached, emphasis is laid on the timely diagnosing of this drug-related damage. Diagnostic procedures have been introduced for early detection of risk patients before the therapy has even commenced. Timely diagnosis of myocardium effects in the course of the conservative cancer therapy allows for adjustment of the oncology therapy and lifestyle and timely commencement of treatment of the affected myocardium. Echocardiograph is considered the basic procedure of patient monitoring during cancer therapy. MRI of the myocardium and CT cardiograph are limited by price and availability despite their uncontentious role in oncocardiology. Radionuclide ventriculography is considered the gold standard of assessment of the left ventricle function. It is well reproducible and widely available in oncology centres. Laboratory diagnostics of toxic damage of the myocardium focuses on cardinal troponins and natriuretic peptides. This examination performance in clinical practice is undemanding and its application in oncology practice increases.

• MeSH
• 3-jodobenzylguanidin MeSH
• antracykliny klasifikace   škodlivé účinky   MeSH
• bevacizumab škodlivé účinky   MeSH
• biologická terapie škodlivé účinky   MeSH
• cílená molekulární terapie klasifikace   škodlivé účinky   MeSH
• echokardiografie metody   MeSH
• elektrokardiografie metody   MeSH
• fluoruracil škodlivé účinky   MeSH
• jednofotonová emisní výpočetní tomografie metody   MeSH
• kardiotoxicita * diagnóza   etiologie   klasifikace   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• myokard patologie   MeSH
• nádory farmakoterapie   komplikace   MeSH
• nemoci srdce diagnostické zobrazování   diagnóza   chemicky indukované   MeSH
• protinádorové látky * klasifikace   škodlivé účinky   MeSH
• radioisotopová ventrikulografie metody   MeSH
• rizikové faktory MeSH
• sunitinib škodlivé účinky   MeSH
• trastuzumab škodlivé účinky   MeSH
• Check Tag
• lidé MeSH

• MeSH
• fagocyty fyziologie   MeSH
• monocyty MeSH
• mononukleární fagocytární systém fyziologie   MeSH
• výzkum MeSH
• výzkumné techniky MeSH

• Konspekt
• Buněčná biologie. Cytologie
• NLK Obory
• cytologie, klinická cytologie
• NLK Publikační typ
• kolektivní monografie

Objective: Anti-lipolytic drugs and exercise are enhancers of growth hormone (GH) secretion. Decreased circulating free fatty acids (FFA) have been proposed to exert ghrelin-GH feedback loop after administration of an anti-lipolytic longer-acting analog of nicotinic acid, Acipimox (OLB, 5-Methylpyrazine-2-carboxylic acid 4-oxide, molecular weight of 154.1 Da). OLB administration strongly suppresses plasma FFA during exercise. Neuroendocrine perturbations of the adipose tissue (AT), gut, and brain peptides may be involved in the etiopathogenesis of eating disorders including bulimia nervosa (BN) and anorexia nervosa. BN is characterized by binge eating, self-induced vomiting or excessive exercise. Approach: To test the hypothesis that treatment with OLB together with exercise vs. exercise alone would induce feedback action of GH, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), and leptin on ghrelin in Czech women with BN and in healthy-weight Czech women (HW). The lipolysis rate (as glycerol release) in subcutaneous abdominal AT was assessed with microdialysis. At an academic medical center, 12 BN and 12 HW (the control group) were randomized to OLB 500 mg 1 h before a single exercise bout (45 min, 2 W/kg of lean body mass [LBM]) once a week vs. identical placebo over a total of 2 weeks. Blood plasma concentrations of GH, PP, PYY, leptin, ghrelin, FFA, glycerol, and concentrations of AT interstitial glycerol were estimated during the test by RIA utilizing 125I-labeled tracer, the electrochemiluminescence technique (ECLIA) or colorimetric kits. Results: OLB administration together with short-term exercise significantly increased plasma GH (P < 0.0001), PP (P < 0.0001), PYY, and leptin concentrations and significantly decreased plasma ghrelin (P < 0.01) concentrations in both groups, whereas short-term exercise with placebo resulted in plasma ghrelin (P < 0.05) decrease exclusively in BN. OLB administration together with short-term exercise significantly lowered local subcutaneous abdominal AT interstitial glycerol (P < 0.0001) to a greater extent in BN. Conclusion: OLB-induced suppression of plasma ghrelin concentrations together with short-term exercise and after the post-exercise recovering phase suggests a potential negative co-feedback of GH, PP, PYY, and leptin on ghrelin secretion to a greater extent in BN. Simultaneously, the exercise-induced elevation in AT interstitial glycerol leading to a higher inhibition of peripheral lipolysis by OLB in BN. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03338387.

• Publikační typ
• časopisecké články MeSH