Haematopoietic toxicity of radium-223 in patients with high skeletal tumour burden.

Unlabelled: In patients with metastasized, castration resistant prostate cancer (mCRPC) treatment with radium-223 (Xofigo) is an attractive therapeutic option. In particular, patients with high tumour load seem to profit from this treatment in regard of survival and quality of live. Aim of this study was to stratify mCRPC patients according to a quantitative imaging marker derived from routine bone scans (EXINI bone) and analyze haematopoietic toxicity of Xofigo in these patients.

Macrophages in collateral arteriogenesis.

Arteriosclerotic vascular disease is the most common cause of death and a major cause of disability in the developed world. Adverse outcomes of arteriosclerotic vascular disease are related to consequences of tissue ischemia and necrosis affecting the heart, brain, limbs, and other organs. Collateral artery growth or arteriogenesis occurs naturally and can help restore perfusion to ischemic tissues.

One single-time-point kidney uptake from OctreoScan correlates with number of desintegrations measured over 72 hours and calculated for the 6.7 hours half-life nuclide (177)Lu.

Aim: In somatostatin receptor-targeted therapy, renal toxicity is an expected side effect, and therefore pretherapeutic dosimetry based on a measured kinetics is preferable. In contrast, a convenient one single-time-point scan might also reveal relevant information on expected dose to organs. However, very early time points might not reflect the true retention by the renal cortex and therefore be of limited value to predict dose for the long-lived 177Lu.

18F-Fluorodeoxyglucose positron-emission tomography (PET) can be used to assess inflammation non-invasively in Crohn's disease.

Background: Differential therapy requires repeated diagnostic assessment for mapping and monitoring of disease activity in Crohn's disease (CD).

Purpose: The purpose of this prospective study was to evaluate the accuracy of (18)F-fluorodexyglucose positron-emission tomography (FDG-PET) for non-invasive assessment of disease activity in CD.

Methods: Forty-three patients with CD underwent ileocolonoscopy and hydromagnetic resonance imaging (hydro-MRI) as reference standards.

6-18F-fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to 123I-metaiodobenzyl-guanidine scintigraphy in the detection of extraadrenal and hereditary pheochromocytomas and paragangliomas: correlation with vesicular monoamine transporter expression.

Context: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) may be better detected by (18)F-fluorodihydroxyphenylalanine-positron emission tomography (FDOPA-PET) than (123)I-metaiodobenzyl-guanidine (123-I-MIBG) scintigraphy.

Objective: The objective of the study was to correlate functional imaging results with immunohistochemical, molecular-genetic, and biochemical findings.

Design And Setting: Thirty consecutive patients with suspected PHEO/PGL presenting at a tertiary referral centre were investigated in a prospective study.

Critical single proximal left arterial descending coronary artery stenosis to mimic chronic myocardial ischemia: a new model induced by minimal invasive technology.

Background/aims: The present report examines a new pig model for progressive induction of high-grade stenosis, for the study of chronic myocardial ischemia and the dynamics of collateral vessel growth.

Methods: Thirty-nine Landrace pigs were instrumented with a novel experimental stent (GVD stent) in the left anterior descending coronary artery. Eight animals underwent transthoracic echocardiography at rest and under low-dose dobutamine.

Continuous endothelial cell activation increases angiogenesis: evidence for the direct role of endothelium linking angiogenesis and inflammation.

There is increasing evidence that chronic inflammation is tightly linked to diseases associated with endothelial dysfunction, including the induction of aberrant angiogenesis. While leukocytes have been described as mediators of inflammation-associated angiogenesis, the effects of direct chronic endothelial activation have not been addressed in this context. Using an uncleavable mutant of the transmembrane form of tumor necrosis factor-alpha (TNF-alpha), we have established models of stable TNF-alpha expression in endothelial cells in vitro and in transgenic mice in vivo.

Impact of mouse strain differences in innate hindlimb collateral vasculature.

Objective: To assess the importance of genetic background for collateral artery development.

Methods And Results: C57BL/6, BALB/c and 129S2/Sv mice were studied after femoral artery ligation by laser Doppler imaging, visible light oximetry, time-of-flight-magnetic resonance imaging, and treadmill testing; C57BL/6 and BALB/c also underwent electron paramagnetic resonance (EPR) oximetry, x-ray angiography, and histology. C57BL/6 had the least initial distal ischemia and most complete recovery.

Delayed arteriogenesis in hypercholesterolemic mice.

Background: Hypercholesterolemia has been reported to inhibit ischemia-induced angiogenesis. To address its effects on arteriogenesis, we investigated arterial growth in hypercholesterolemic low-density lipoprotein receptor(-/-)/ApoB-48(-/-) (HCE) mice.

Methods And Results: The extent and the time course of arteriogenesis after femoral artery ligation was evaluated in HCE and strain-matched control mice.

Demonstration of pulmonary beta2-adrenergic receptor binding in vivo with [18F]fluoroethyl-fenoterol in a guinea pig model.

Purpose: The new beta2 radioligand (R,R)(S,S) 5-(2-(2-[4-(2-[18F]fluoroethoxy)phenyl]-1-methylethylamino)-1-hydroxyethyl)-benzene-1,3-diol ([18F]FE-fenoterol; [18F]FEFE), a fluoroethylated derivative of racemic fenoterol, was evaluated in vivo and ex vivo using a guinea pig model.

Methods: Dynamic PET studies over 60 min with [(18)F]FEFE were performed in nine Hartley guinea pigs in which a baseline (group 1, n=3), a predose (group 2, n=3; 2 mg/kg fenoterol 5 min prior to injection of [18F]FEFE) or a displacement study (group 3, n=3; 2 mg/kg fenoterol 5 min post injection of [18F]FEFE) was conducted.

Results: In all animal groups, the lungs could be visualised and semi-quantified separately by calculating uptake ratios to non-specific binding in the neck area.

Synthesis of anticoagulantly active heparan sulfate proteoglycans by glomerular epithelial cells involves multiple 3-O-sulfotransferase isoforms and a limiting precursor pool.

Endothelial and other select cell types synthesize a subpopulation of heparan sulfate (HS) proteoglycans (HSPGs), anticoagulant HSPGs (aHSPGs) that bear aHS-HS chains with the cognate 3-O-sulfated pentasaccharide motif that can bind and activate anti-thrombin (AT). Endothelial cells regulate aHSPG production by limiting levels of HS 3-O-sulfotransferase-1 (3-OST-1), which modifies a non-limiting pool of aHS-precursors. By probing kidney cryosections with (125)I-AT and fluorescently tagged AT we found that the glomerular basement membrane contains aHSPGs, with the staining pattern implicating synthesis by glomerular epithelial cells (GECs).

[Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome: conceptual chances].

The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse.

Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours.

Purpose: For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with 90Y is frequently used [90Y-DOTA-Phe1-Tyr3)-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical 86Y-DOTA-Phe1-Tyr3-octreotide (considered as the gold standard) and the commercially available 111In-pentetreotide.

Time-of-flight quantitative measurements of blood flow in mouse hindlimbs.

Purpose: To evaluate the feasibility of using time-of-flight (TOF) imaging to directly measure hindlimb blood flow in a mouse model of peripheral vascular disease.

Materials And Methods: Four tubes were imaged simultaneously (diameters = 0.39 mm, 0.

Magnetic resonance angiography of collateral vessels in a murine femoral artery ligation model.

The in vivo detection of growing collateral vessels following arterial occlusion is difficult in small animals. We have addressed the feasibility of performing high resolution time-of-flight angiograms to monitor the growth of collateral vessels after femoral artery occlusion in mice. We will also present a low-pass quadrature birdcage coil construction with a sufficient signal-to-noise ratio to produce high resolution.

Thromboxane A2 receptor agonists antagonize the proangiogenic effects of fibroblast growth factor-2: role of receptor internalization, thrombospondin-1, and alpha(v)beta3.

Thromboxane (TX) A2 is released from multiple cell types and is a prime mediator of the pathogenesis of many vascular events, including angiogenesis. Endothelial cells express TXA2 receptors (TP) but the effects of TP stimulation on angiogenesis remain controversial. In this study, we show that stimulation of endothelial cell TP impairs ligand-induced FGF receptor internalization and consequently abrogates FGF-2-induced endothelial cell migration in vitro and angiogenesis in vivo.

Collateral artery growth (arteriogenesis) after experimental arterial occlusion is impaired in mice lacking CC-chemokine receptor-2.

Arteriogenesis has been associated with the presence of monocytes/macrophages within the collateral vessel wall. Induced macrophage migration in vivo is driven by the binding of monocyte chemoattractant protein-1 (MCP-1, or CCL2 in the new nomenclature) to the CCR2-chemokine receptor on macrophages. To determine whether the CCL2-CCR2 signaling pathway is involved in the accumulation of macrophages in growing collateral vessels, we used mice that are deficient in CCR2 in a model of experimental arterial occlusion and collateral vessel growth.

Surveillance of basaloid oral squamous cell carcinoma: the value of [18F]FDG-PET.

Basaloid squamous cell carcinoma (BSCC) represents a rare but exceptionally aggressive variant of oral cancer. Hence, when tumors have been characterized to belong to this specific high-risk subpopulation, it remains an open issue how to manage the patients in terms of diagnostic surveillance and reconstruction. Therefore we explored whether glucose metabolism as measured by [18F]FDG-PET can accurately assess the disease status in the follow up of oral BSCC.

Inhibition of collateral artery growth by mibefradil: possible role of volume-regulated chloride channels.

Endothelial cell swelling is one of the earliest hallmarks of arteriogenesis, the growth and maturation of collaterals. Mibefradil was found to block endothelial Cl(-) channels that control the volume of endothelial cells. Thus the authors investigated whether the blockade of volume-controlling endothelial cell channels would translate into an inhibition of arteriogenesis.

Bone marrow-derived cells do not incorporate into the adult growing vasculature.

Bone marrow-Derived cells have been proposed to form new vessels or at least incorporate into growing vessels in adult organisms under certain physiological and pathological conditions. We investigated whether bone marrow-Derived cells incorporate into vessels using mouse models of hindlimb ischemia (arteriogenesis and angiogenesis) and tumor growth. C57BL/6 wild-type mice were lethally irradiated and transplanted with bone marrow cells from littermates expressing enhanced green fluorescent protein (GFP).