Acute Myelomonoblastic Leukemia (My1/De): A Preclinical Rat Model.

Background/aim: Since acute myeloid leukemias still represent the most aggressive type of adult acute leukemias, the profound understanding of disease pathology is of paramount importance for diagnostic and therapeutic purposes. Hence, this study aimed to explore the real-time disease fate with the establishment of an experimental myelomonoblastic leukemia (My1/De) rat model using preclinical positron emission tomography (PET) and whole-body autoradiography.

Materials And Methods: In vitro [F]F-FDG uptake studies were performed to compare the tracer accumulation in the newly cultured My1/De tumor cell line (blasts) with that in healthy control and My1/De bone marrow suspensions.

Synthesis, Physicochemical, Labeling and In Vivo Characterization of Sc-Labeled DO3AM-NI as a Hypoxia-Sensitive PET Probe.

Hypoxia promotes angiogenesis, which is crucial for tumor growth, and induces malignant progression and increases the therapeutic resistance. Positron emission tomography (PET) enables the detection of the hypoxic regions in tumors using 2-nitroimidazole-based radiopharmaceuticals. We describe here a physicochemical study of the Sc(DO3AM-NI) complex, which indicates: (a) relatively slow formation of the Sc(DO3AM-NI) chelate in acidic solution; (b) lower thermodynamic stability than the reference Sc(DOTA); (c) however, it is substantially more inert and consequently can be regarded as an excellent Sc-binder system.

Imaging of Neo-angiogenesis of Transplanted Metastases in Subrenal Capsule Assay Induced Rat Model.

Background/aim: Changes in the expression of neo-angiogenic molecules in the primary tumor and its metastases may significantly affect the efficacy of therapies. The aim of this study was to evaluate the alterations in aminopeptidase N (APN/CD13) and αβ integrin receptor expression in serially transplanted mesoblastic nephroma tumor (Ne/De) metastases using Gallium (Ga)-labeled NOTA-cNGR and NODAGA-RGD radiotracers and preclinical positron emission tomography (PET) imaging.

Materials And Methods: Primary and metastatic mesoblastic nephroma (Ne/De) tumors were induced by subrenal capsule assay (SRCA) in Fischer-344 rats.

Imaging of Ischemia/Reperfusion-mediated Aminopeptidase N Expression in Surgical Rat Model Using Ga-NOTA-c(NGR).

Background/aim: Previous studies have already shown that Gallium(Ga)-labeled NGR-based radiopharmaceuticals specifically bind to the neoangiogenic molecule Aminopeptidase N (APN/CD13). The aim of this study was to evaluate the applicability of Ga-NOTA-c(NGR) in the in vivo detection of the temporal changes of APN/CD13 expression in the diabetic retinopathy rat model using positron emission tomography (PET).

Materials And Methods: Ischemia/reperfusion injury was initiated by surgical ligation of the left bulbus oculi of rats.

Synthesis of Ga-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.

In vivo preclinical assessment of novel Ga-labelled peptides for imaging of tumor associated angiogenesis using positron emission tomography imaging.

Formation and growth of metastases require a new vascular network. Angiogenesis plays an essential role in the expansion and progression of most malignancies. A high number of molecular pathways regulate angiogenesis, including vascular endothelial growth factor (VEGF), αβ integrin, matrix metalloproteinases (MMPs), or aminopeptidase N.

Molecular Imaging of the Efficacy of Aminopeptidase N (APN/CD13) Receptor Inhibitor Treatment on Experimental Tumors Using Ga-NODAGA-c(NGR) Peptide.

Introduction: The aminopeptidase N (APN/CD13) receptor plays an important role in the neoangiogenic process and metastatic tumor cell invasion. Clinical and preclinical studies reported that bestatin and actinonin are cytotoxic to APN/CD13-positive tumors and metastases due to their APN/CD13-specific inhibitor properties. Our previous studies have already shown that Ga-labeled NGR peptides bind specifically to APN/CD13 expressing tumor cells.

In vivo assessment of aminopeptidase N (APN/CD13) specificity of different Ga-labelled NGR derivatives using PET/MRI imaging.

Aminopeptidase N (APN/CD13) plays an important role in neoangiogenic process in malignancies. Our previous studies have already shown that Ga-labelled NOTA conjugated asparagine-glycine-arginine peptide (c[KNGRE]-NH) specifically bind to APN/CD13 expressing tumors. The aim of this study was to evaluate and compare the APN/CD13 specificity of newly synthesized Ga-labelled NGR derivatives in vivo by PET/MRI imaging using hepatocellular carcinoma (He/De) and mesoblastic nephroma (Ne/De) tumor models.

Radiosynthesis and Preclinical Investigation of C-Labelled 3-(4,5-Diphenyl-1,3-oxazol-2-yl)propanal Oxime ([ C]SZV 1287).

The radiosynthesis, as well as the in vivo and ex vivo biodistribution of the C radiolabelled 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime (6, [ C]SZV 1287) are reported. SZV 1287 is a novel semicarbazide-sensitive amine oxidase (SSAO) inhibitor and a promising candidate to be a novel analgesic for the treatment of neuropathic pain. Its radiolabelling was developed via a four-step radiosynthesis which started from the reaction of a Grignard reagent with [ C]CO to produce [ C]oxaprozin (3).

Imaging of Hypoxia and Neoangiogenesis in Experimental Syngeneic Hepatocellular Carcinoma Tumor Model Using Positron Emission Tomography.

Introduction: Hypoxia-induced integrin and aminopeptidase N (APN/CD13) receptor expression play an important role in tumor neoangiogenesis. APN/CD13-specific Ga-NOTA-c(NGR), integrin-specific Ga-NODAGA-[c(RGD)], and hypoxia-specific Ga-DOTA-nitroimidazole enable the detection of the neoangiogenic process and the hypoxic regions in the tumor mass using positron emission tomography (PET) imaging. The aim of this study was to evaluate whether Ga-NOTA-c(NGR) and Ga-DOTA-nitroimidazole allow the noninvasive detection of the temporal changes of APN/CD13 expression and hypoxia in experimental He/De tumors using positron emission tomography.

In vivo preclinical evaluation of the new Ga-labeled beta-cyclodextrin in prostaglandin E2 (PGE2) positive tumor model using positron emission tomography.

The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway plays an important role in tumor development and formation of metastases. It was earlier reported that cyclodextrin derivatives have a high affinity to form complexes with PGE2. Based on these results radiolabeled cyclodextrins - as new radiopharmaceuticals - may open a new pathway in the in vivo imaging and diagnosis of PGE2 positive tumors.

Preclinical evaluation of melanocortin-1 receptor (MC1-R) specific Ga- and Sc-labeled DOTA-NAPamide in melanoma imaging.

Purpose: Alpha melanocyte stimulating hormone (α-MSH) enhances melanogenesis in melanoma malignum by binding to melanocortin-1 receptors (MC1-R). Earlier studies demonstrated that alpha-MSH analog NAPamide molecule specifically binds to MC1-R receptor. Radiolabeled NAPamide is a promising radiotracer for the non-invasive detection of melanin producing melanoma tumors by Positron Emission Tomography (PET).

Imaging of Experimental Melanoma Tumors using the Novel Radiotracer Ga-NODAGA-Procainamide (PCA).

Purpose: The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment.

Comparative preclinical evaluation of Ga-NODAGA and Ga-HBED-CC conjugated procainamide in melanoma imaging.

Malignant melanoma is the most aggressive form of skin cancer. The early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of this disease. Previous studies have shown that benzamide derivatives (e.

In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer (68)Ga-NOTA-c(NGR).

Purpose: Aminopeptidase N (APN/CD13) plays an important role in tumor neoangiogenic process and the development of metastases. Furthermore, it may serve as a potential target for cancer diagnosis and therapy. Previous studies have already shown that asparagine-glycine-arginine (NGR) peptides specifically bind to APN/CD13.

Deletion of the metabolic transcriptional coactivator PGC1β induces cardiac arrhythmia.

Aims: Peroxisome proliferator-activated receptor-γ coactivators PGC1α and PGC1β modulate mitochondrial biogenesis and energy homeostasis. The function of these transcriptional coactivators is impaired in obesity, insulin resistance, and type 2 diabetes. We searched for transcriptomic, lipidomic, and electrophysiological alterations in PGC1β(-/-) hearts potentially associated with increased arrhythmic risk in metabolic diseases.

Defective peroxisomal proliferators activated receptor gamma activity due to dominant-negative mutation synergizes with hypertension to accelerate cardiac fibrosis in mice.

Aims: Humans with inactivating mutations in peroxisomal proliferators activated receptor gamma (PPARgamma) typically develop a complex metabolic syndrome characterized by insulin resistance, diabetes, lipodystrophy, hypertension, and dyslipidaemia which is likely to increase their cardiovascular risk. Despite evidence that the activation of PPARgamma may prevent cardiac fibrosis and hypertrophy, recent evidence has suggested that pharmacological activation of PPARgamma causes increased cardiovascular mortality. In this study, we investigated the effects of defective PPARgamma function on the development of cardiac fibrosis and hypertrophy in a murine model carrying a human dominant-negative mutation in PPARgamma.

Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance.

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1beta) has been implicated in important metabolic processes. A mouse lacking PGC-1beta (PGC1betaKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1betaKO mice are generally viable and metabolically healthy.

Limitation of myocardial reperfusion injury by AMP579, an adenosine A1/A2A receptor agonist: role of A2A receptor and Erk1/2.

AMP579, an adenosine A(1)/A(2A) receptor agonist, protects against myocardial infarction when given at the onset of reperfusion. However, it is unclear which receptor subtype mediates its protective actions. Anaesthetised rabbits were subjected to 30 min regional ischaemia/180 min reperfusion in vivo.

Second window of protection following myocardial preconditioning: an essential role for PI3 kinase and p70S6 kinase.

Ischaemic preconditioning (IPC) protects the heart against myocardial infarction acutely as well as several hours later (e.g. 24-48 h).

Role of nuclear factor-kappa B activation in acute ischaemia-reperfusion injury in myocardium.

(1) Our aims were to characterize activation of the transcription factor, nuclear factor kappa-B(NF-kappaB), during myocardial ischaemia-reperfusion and to assess its functional role in the evolution of acute ischaemia-reperfusion injury in intact myocardium in vivo. (2) Under pentobarbitone anaesthesia, rabbits underwent sham operation, 30 min left coronary artery occlusion followed by 0, 10 or 180 min reperfusion. Saline or NF-kappaB inhibitor diethyldithiocarbamic acid (DDTC, 50, 100 or 200 mg kg(-1)) was given intravenously 5 min prior to reperfusion.