WorldWideScience

Sample records for hypoxic imaging agents

  1. Preparation of hypoxic imaging agents 99Tcm-MNLS and 99Tcm-MLS and their biodistribution in mice

    International Nuclear Information System (INIS)

    Zha Zhihao; Wang Jianjun; Zhu Lin

    2009-01-01

    To develop 99 Tc m labeled hypoxic agents,two phosphate-based chelating agents were coupled to metronidazole, 2- (2-methyl-5-nitro-1H-imidazol-1-yl) ethyl dihydrogen phosphate (MNLS) and its analog 2- (2-methyl-1H-imidazol-1-yl) ethyl dihydrogen phosphate (MLS) were synthesized based on the mechanism of prodrug. Labeling yield of these 99 Tc m complexes were more than 90% as proved by TLC. Paper electrophoresis showed that these complexes were neutral. Biodistribution of these complexes in tumor-bearing mice showed that the uptake of 99 Tc m -MNLS (120 min, 2.99 ± 0.25 ID%/g) in tumor was higher than that of 99 Tc m -HL91 (120 min, 0.93 ± 0.13 ID%/g) and 99 Tc m -MLS (120 min, 1.61 ± 0.13 ID%/g), and the uptake ratio of tumor to muscle and tumor to liver of 99 Tc m -MNLS (120 min, 5.90, 1.03) were higher than that of 99 Tc m -HL91 (120 min, 3.59, 0.17) and 99 Tc m -MLS (120 min, 5.40, 0.13). The higher tumor uptake for 99 Tc m -MNLS than 99 Tc m -MLS suggested that nitroimidazole was a key group for tumor accumulation. 99 Tc m -MNLS had higher tumor uptake and lower liver uptake, which had the potential for tumor imaging and was worth of further vestigation. (authors)

  2. Adrenal imaging agents

    International Nuclear Information System (INIS)

    Davis, M.A.; Hanson, R.N.; Holman, B.L.

    1980-01-01

    The goals of this proposal are the development of selenium-containing analogs of the aromatic amino acids as imaging agents for the pancreas and of the adrenal cortex enzyme inhibitors as imaging agents for adrenal pathology. The objects for this year include (a) the synthesis of methylseleno derivatives of phenylalanine and tryptophan, and (b) the preparation and evaluation of radiolabeled iodobenzoyl derivatives of the selenazole and thiazole analogs of metyrapone and SU-9055

  3. Development of a real-time imaging system for hypoxic cell apoptosis

    Directory of Open Access Journals (Sweden)

    Go Kagiya

    2016-01-01

    Full Text Available Hypoxic regions within the tumor form due to imbalances between cell proliferation and angiogenesis; specifically, temporary closure or a reduced flow due to abnormal vasculature. They create environments where cancer cells acquire resistance to therapies. Therefore, the development of therapeutic approaches targeting the hypoxic cells is one of the most crucial challenges for cancer regression. Screening potential candidates for effective diagnostic modalities even under a hypoxic environment would be an important first step. In this study, we describe the development of a real-time imaging system to monitor hypoxic cell apoptosis for such screening. The imaging system is composed of a cyclic luciferase (luc gene under the control of an improved hypoxic-responsive promoter. The cyclic luc gene product works as a caspase-3 (cas-3 monitor as it gains luc activity in response to cas-3 activation. The promoter composed of six hypoxic responsible elements and the CMV IE1 core promoter drives the effective expression of the cyclic luc gene in hypoxic conditions, enhancing hypoxic cell apoptosis visualization. We also confirmed real-time imaging of hypoxic cell apoptosis in the spheroid, which shares properties with the tumor. Thus, this constructed system could be a powerful tool for the development of effective anticancer diagnostic modalities.

  4. Attenuation of hypoxic current by intracellular applications of ATP regenerating agents in hippocampal CA1 neurons of rat brain slices.

    Science.gov (United States)

    Chung, I; Zhang, Y; Eubanks, J H; Zhang, L

    1998-10-01

    Hypoxia-induced outward currents (hyperpolarization) were examined in hippocampal CA1 neurons of rat brain slices, using the whole-cell recording technique. Hypoxic episodes were induced by perfusing slices with an artificial cerebrospinal fluid aerated with 5% CO2/95% N2 rather than 5% CO2/95% O2, for about 3 min. The hypoxic current was consistently and reproducibly induced in CA1 neurons dialysed with an ATP-free patch pipette solution. This current manifested as an outward shift in the holding current in association with increased conductance, and it reversed at -78 +/- 2.5 mV, with a linear I-V relation in the range of -100 to -40 mV. To provide extra energy resources to individual neurons recorded, agents were added to the patch pipette solution, including MgATP alone, MgATP + phosphocreatine + creatine kinase, or MgATP + creatine. In CA1 neurons dialysed with patch solutions including these agents, hypoxia produced small outward currents in comparison with those observed in CA1 neurons dialysed with the ATP-free solution. Among the above agents examined, whole-cell dialysis with MgATP + creatine was the most effective at decreasing the hypoxic outward currents. We suggest that the hypoxic hyperpolarization is closely related to energy metabolism in individual CA1 neurons, and that the energy supply provided by phosphocreatine metabolism may play a critical role during transient metabolic stress.

  5. Nicotinamide and other benzamide analogs as agents for overcoming hypoxic cell radiation resistance in tumours

    International Nuclear Information System (INIS)

    Horsman, M.

    1996-01-01

    Oxygen deficient hypoxic cells, which are resistant to sparsely ionising radiation, have now been identified in most animal and some human solid tumours and will influence the response of those tumours to radiation treatment. This hypoxia can be either chronic, arising from an oxygen diffusion limitation, or acute, resulting from transient stoppages in microregional blood flow. Extensive experimental studies, especially in the last decade, have shown that nicotinamide and structurally related analogs can effectively sensitize murine tumours to both single and fractionated radiation treatments and that they do so in preference to the effects seen in mouse normal tissues. The earliest studies suggested that this enhancement of radiation damage was the result of an inhibition of the repair mechanisms. However, recent studies in mouse tumours have shown that these drugs prevent transient cessations in blood flow, thus inhibiting the development of acute hypoxia. This novel discovery led to the suggestion that the potential role of these agents as radiosensitizers would be when combined with treatments that overcame chronic hypoxia. The combined nicotinamide with hyperthermia proved that the enhancement of radiation damage by both agents together was greater than that seen with each agent alone. Similar results were later seen for nicotinamide combined with a perfluorochemical emulsion, carbogen breathing, and pentoxifylline, and in all these studies the effects in tumours were always greater than those seen in appropriate normal tissues. Of all the analogs, it is nicotinamide itself which has been the most extensively studied as a radiosensitizer in vivo and the one that shows the greatest effect in animal tumours. It is also an agent that has been well established clinically, with daily doses of up to 6 g, associated with a low incidence of side effects. This human dose is equivalent to 100-200 mg/kg in mice and such doses will maximally sensitize murine tumours to

  6. The feasibility of a targeted ultrasound contrast agent carrying genes and cell-penetrating peptides to hypoxic HUVEC

    International Nuclear Information System (INIS)

    Tian Ju; Wang Zhigang; Ren Jianli; Zhang Qingfeng; Liu Li

    2012-01-01

    Objective: To prepare an anti-P-selectin targeted ultrasound contrast agent carrying genes and cell-penetrating peptides (CPP) and to investigate its feasibility of delivery to hypoxic human umbilical vein endothelial cells (HUVEC). Methods: Anti-P-selectin targeted ultrasound contrast agent carrying a green fluorescent protein gene (pEGFP-N1) and CPP was prepared by mechanical vibration and carbodiimide techniques. The appearance, distribution, concentration and diameter of the ultrasound contrast agent were measured. The gene and CPP distribution on the agent was investigated using confocal laser scanning microscopy (CLSM). The efficiency of the ultrasound contrast agent to carry the gene and CPP was investigated by fluorospectrophotometry. HUVEC were cultured in vitro and hypoxic HUVEC were prepared using hydrogen peroxide (H 2 O 2 ). Hypoxic HUVEC were randomly assigned targeted ultrasound contrast agents and non-targeted ultrasound contrast agents for transfection. The transfection effect of green fluorescent protein in the two groups was observed using fluorescence microscopy and flow cytometry. T-test and linear correlation analysis were used for statistical analysis. Results: The average diameter of anti-P-selectin targeted ultrasound contrast agents carrying gene and CPP was (2.15 ±0.36) μm and the concentration was (1.58 ± 0.23) × 10 7 /ml.The results of CLSM showed that gene and CPP were distributed on the shell of the agent. The gene encapsulation efficiency was 28% (y=0.932x-0.09, r=0.993, P<0.05), and the CPP encapsulation efficiency was 25% (y=5.875x-0.81, r=0.987, P<0.05). EGFP expression was observed using fluorescence microscopy in targeted ultrasound contrast agents and non-targeted ultrasound contrast agents. The average transfection efficiencies of targeted ultrasound contrast agents and non-targeted ultrasound contrast agents were (18.74 ± 0.47) % and (15.34 ± 0.22) % after 24 h (t=10.923, P<0.001). Conclusions: The in vitro studies

  7. Synthesis and radiolabelling of novel nitrogen mustards for the imaging of hypoxic tissue

    International Nuclear Information System (INIS)

    Falzon, C.; Ackermann, U.; Tochon-Danguy, H.J.; O'Keefe, G.J.; White, J.; Spratt, N.; Howells, D.; Scott, A.M.

    2005-01-01

    Hypoxic tissue is of great significance in stroke and oncology. Among the radiotracers currently used to detect hypoxia, derivatives based on the 2-nitro-imidazole ring such as FMISO or FAZA have received considerable attention in medical imaging. Unfortunately, due to slow clearance of these tracers from normoxic tissue a waiting period of two hours is required between tracer injection and the scanning of the patient. In addition the target to background ratio is low and the quality of the image is therefore poor. Nitrogen mustards are another class of compounds that have great affinity to hypoxic tissue. Derivatives of these compounds labelled with a positron emitting radionuclide, such as [ 18 F], may allow for the imaging of hypoxic regions in the ischemic penumbra. It therefore, may be a useful diagnostic tool in stroke. Radiolabeled N-(2-[ 18 F]-fluoroethyl)-N-(2-chloroethyl)-4-methylsulfinylaniline was successfully synthesised using a potassium fluoride kryptofix complex, giving the desired product in 40% radiochemical yield (10 min at 100 Degrees C). In vitro analysis to determine the stability of the radiotracer in plasma and saline indicated no defluorination. Biological evaluation studies of the radiotracer were undertaken using a rat stroke model (Middle cerebral Arterial Occlusion (MCAO)) to determine whether the ischemic penumbra can be imaged using PET. 150//Ci (5.5MBq) of the radiotracer was injected into the tail vein of the rat immediately after the MCAO. The rat was sacrificed 2 hours post injection and ex-vivo autoradiography was performed. Uptake of the radiotracer was observed in hypoxic regions of the brain (n=6). Dynamic PET images revealed that the ischemic penumbra can be imaged 15 minutes post injection of this tracer. With these promising results, we are now synthesizing other analogues to determine their relationship between selectivity for hypoxic tissue and brain uptake

  8. In vivo evaluation of a radiogallium-labeled bifunctional radiopharmaceutical, Ga-DOTA-MN2, for hypoxic tumor imaging.

    Science.gov (United States)

    Sano, Kohei; Okada, Mayumi; Hisada, Hayato; Shimokawa, Kenta; Saji, Hideo; Maeda, Minoru; Mukai, Takahiro

    2013-01-01

    On the basis of the findings obtained by X-ray crystallography of Ga-DOTA chelates and the drug design concept of bifunctional radiopharmaceuticals, we previously designed and synthesized a radiogallium-labeled DOTA chelate containing two metronidazole moieties, (67)Ga-DOTA-MN2, for hypoxic tumor imaging. As expected, (67)Ga-DOTA-MN2 exhibited high in vivo stability, although two carboxyl groups in the DOTA skeleton were conjugated with metronidazole moieties. In this study, we evaluated (67/68)Ga-DOTA-MN2 as a nuclear imaging agent for hypoxic tumors. (67)Ga-labeling of DOTA-MN2 with (67)GaCl(3) was achieved with high radiochemical yield (>85%) by 1-min of microwave irradiation (50 W). The pharmacokinetics of (67)Ga-DOTA-MN2 were examined in FM3A tumor-bearing mice, and compared with those of (67)Ga-DOTA-MN1 containing one metronidazole unit and (67)Ga-DOTA. Upon administration, (67)Ga-DOTA-MN2 exhibited higher accumulation in the implanted tumors than (67)Ga-DOTA. Tumor-to-blood ratios of (67)Ga-DOTA-MN2 were about two-fold higher than those of (67)Ga-DOTA-MN1. Autoradiographic analysis showed the heterogeneous localization of (67)Ga-DOTA-MN2 in the tumors, which corresponds to hypoxic regions suggested by well-established hypoxia marker drug, pimonidazole. Furthermore, in positron emission tomography (PET) study, the tumors of mice administered (68)Ga-labeled DOTA-MN2 were clearly imaged by small-animal PET at 1 h after administration. This study demonstrates the potential usefulness of (67/68)Ga-DOTA-MN2 as a nuclear imaging agent for hypoxic tumors and suggests that two functional moieties, such as metronidazole, can be conjugated to radiogallium-DOTA chelate without reducing the complex stability. The present findings provide useful information about the chemical design of radiogallium-labeled radiopharmaceuticals for PET and single photon emission computed tomography (SPECT) studies.

  9. Scintigraphic imaging of focal hypoxic tissue: development and clinical applications of 123I-IAZA

    Directory of Open Access Journals (Sweden)

    Leonard I. Wiebe

    2002-09-01

    Full Text Available Affected tissues in a number of diseases, including cancer, stroke, cardiac infarction and diabetes, develop focal tissue hypoxia during their progression. The presence of hypoxic tissue may make the disease refractory to therapy, as in the case of solid tumor therapy using low LET ionizing radiation. In other pathologies, the detection of viable but hypoxic tissues may serve as a prodromal indicator of developing disease (e.g. diabetes,or as a prognostic indicator for management of the disease (e.g. stroke. Over the past two decades, a number of hypoxia radioimaging agents have been developed and tested clinically. Of these, 18F-Fmiso and 123I-IAZA are the most widely used radiotracers for PET and SPECT/planar imaging, respectively. IAZA and Fmiso are a 2-nitroimidazoles that chemically bind to subcellular components of viable hypoxic tissues. They sensitize hypoxic tumour to the killing effects of ionizing radiation via mechanisms that mimic the radiosensitizing effects of oxygen, and are therefore called oxygen mimetics. The oxygen mimetic effect is attributable in large part to the covalent binding of reductively-activated nitroimidazole intermediates to critical cellular macromolecules. Nitroimidazoles labelled with gamma-emitting radionuclides (e.g. 18F-Fmiso and 123I-IAZA have been used as scintigraphic markers of tumour hypoxia, based on the need to identify radioresistant hypoxic tumour cells as part of the radiotherapy planning process. Broader interest in non-invasive, imaging-based identification of focal hypoxia in a number of diseases has extended hypoxia studies to include peripheral vascular disease associated with diabetes, rheumatoid arthritis, stroke, myocardial ischaemia, brain trauma and oxidative stress. In this review, the current status of hypoxia-selective studies with 123I-IAZA , an experimental diagnostic radiopharmaceutical, is reviewed with respect to its pre-clinical development and clinical applications.Os tecidos

  10. Imaging and Targeting of Hypoxic Tumor Cells with Use of HIF-1-2

    International Nuclear Information System (INIS)

    Kizaka-Kondoh, Shinae; Harada, Hiroshi; Tanaka, Shotaro; Hiraoka, Masahiro

    2006-01-01

    This paper describes imaging (visualization) of transplanted tumor cells under hypoxia in vivo and molecular targeting to kill those cells by inducing their apoptosis. HIF (hypoxia inducible factor) concerned with angiogenesis is induced specifically in hypoxic tumor cells and its activity can be visualized by transfection of reporter vector construct of fluorescent protein GFP or luciferase. Authors established the transfected tumor cells with the plasmid p5HRE-luciferase and when transplanted in the nude mouse, those cells emitted light dependently to their hypoxic conditions, which could be visualized by in vivo imaging system (IVIS) with CCD camera. Authors prepared the oxygen-dependent degradation-procaspase 3-fusion protein (TOP3) to target the hypoxic tumor cells for enhancing their apoptotic signaling, whose apoptosis was actually observed by the IVIS. Reportedly, radiation transiently activates HIF-1 and combination treatment of radiation and TOP3 resulted in the enhanced death of tumor cells. Interestingly, the suppression of tumor growth lasted longer than expected, probably due to inhibition of angiogenesis. Authors called this anti-tumor strategy as the micro-environmental targeting. (T.I.)

  11. Tc-99m imaging agents

    International Nuclear Information System (INIS)

    Weininger, J.; Trumper, J.

    1984-01-01

    A wide range of pharmaceuticals for labeling with Tc-99m, developed by the Soreq Radiopharmaceuticals Department, is described. Details of the production and quality control of 13 kits are given, as well as the range of results required for consistently high quality imaging agents

  12. Preliminary study on hypoxic-ischemic encephalopathy in neonates with diffusion-weighted MR imaging

    International Nuclear Information System (INIS)

    Wang Xiaoming; Chen Liying; Lin Nan; Guo Qiyong

    2005-01-01

    Objective: To evaluate hypoxic-ischemic encephalopathy (HIE) in neonates with diffusion-weighted MR imaging, and to explore the value and limitation of diffusion-weighted imaging (DWI) compared with conventional magnetic resonance imaging. Methods: Conventional magnetic resonance T 1 -weighted imaging (T 1 WI) and DWI (b=700 s/mm 2 ) were performed in 36 neonates with HIE (average age, 8.44 days; range, 3 hours to 22 days), and the cortex and subcortical white matter, deep white matter, basal ganglia and thalamus, cerebral ventricle, and extra-cerebral interspace etc were observed. Results: Signal abnormalities were shown on DWI with hypoxic-ischemic insults, which included diffuse brain damage (19.4%, 7/36): extensive high signals in the regional cortex, subcortical and deep white matter; localized brain damage: high signals along lateral ventricular wall and triangular part (27.8%, 10/36 ), and punctate high signals in the frontal deep white matter (5.6%, 2/36). On T 1 WI, the incidence of the corresponding changes were 16.7% (6/36), 36.1% (13/36), and 30.6%(11/36), respectively. Hemorrhagic lesions demonstrated high signals on T 1 WI and no signals on DWI. Conclusion: DWI was applicable for acute HIE, and T 1 WI was suitable for subacute and chronic HIE. (authors)

  13. Autoradiographic imaging of cerebral ischemia using hypoxic marker: Tc-99m-HL91 in animal models

    International Nuclear Information System (INIS)

    Jiang, N.Y.; Zhu, C.S.; Hu, X.K.

    2002-01-01

    Objective: To explore the possibility of Tc-99m-HL91 imaging in detecting the ischemic penumbra during acute stoke. Methods: 16 Sprague-Dawley (SD) rats were divided into operation group (n=12) and pseudo-operation group (n=4) randomly. In operation group, 12 middle cerebral artery occlusion animal (MCAO) models were established by electrocautery. 4 rats in pseudo-operation group were treated as a control without occlusion. All animals were injected Tc-99m-HL91 intravenously 2 hours after occlusion. Animals were killed at different time after injection and brains were removed rapidly from the skull to do the autoradiographic study. Result: The ischemic territory accumulated more Tc-99m-HL91 than the opposite site in the autoradiogram at 1 hour after injection. The ischemic cerebral tissue can be visualized clearly. At 2, 4 hours after injection, the difference of accumulation of Tc-99m-HL91 in target and non-target site became more obvious. By using computer-enhanced imaging analysis, the optical density (OD) ratio differences between each subgroup of operation group and pseudo-operation group were all significant. Conclusion : Tc-99m-HL91 can be avidly taken up by ischemic penumbra. Tc-99m-HL91 is a potential agent for imaging hypoxic tissue, and Tc-99m-HL91 SPECT may be a promising imaging method in detecting the ischemic penumbra

  14. Autoradiographic imaging of cerebral ischaemia using hypoxic marker: 99mTc-HL91 in animal models

    International Nuclear Information System (INIS)

    Ningyi, J.; Cansheng, Z.; Xiaoke, H.

    2002-01-01

    Objective: To explore the possibility of 99mTc-HL91 imaging in detecting the ischemic penumbra during acute stoke. Methods 16 Sprague-Dawley (SD) rats were divided into operation group (n=12) and pseudo-operation group (n=4) randomly. In operation group, 12 middle cerebral artery occlusion animal (MCAO) models were established by electrocautery. 4 rats in pseudo-operation group were treated as a control without occlusion. All animals were injected 99mTc-HL91 intravenously 2 hours after occlusion. Animals were killed at different time after injection and brains were removed rapidly from the skull to do the autoradiographic study. Result The ischemic territory accumulated more 99mTc-HL91 than the opposite site in the autoradiogram at 1 hour after injection. The ischemic cerebral tissue can be visualized clearly. At 2, 4 hours after injection, the difference of accumulation of 99mTc-HL91 in target and non-target site became more obvious. By using computer-enhanced imaging analysis, the optical density (OD) ratio differences between each subgroup of operation group and pseudo-operation group were all significant. Conclusion 99mTc-HL91 can be avidly taken up by ischemic penumbra. 99mTc-HL91 is a potential agent for imaging hypoxic tissue, and 99mTc-HL91 SPECT may be a promising imaging method in detecting the ischemic penumbra

  15. Prostate Activated Prodrugs and Imaging Agents

    National Research Council Canada - National Science Library

    Jones, Graham B

    2004-01-01

    .... The substrate chosen was a 3 component system composed of a peptide sequence with affinity for PSA, an imaging agent and a deactivating bridge-linker, which electronically incapacitates the imaging agent...

  16. Imaging tumor hypoxia: Blood-borne delivery of imaging agents is fundamentally different in hypoxia subtypes

    Directory of Open Access Journals (Sweden)

    Peter Vaupel

    2014-03-01

    Full Text Available Hypoxic tissue subvolumes are a hallmark feature of solid malignant tumors, relevant for cancer therapy and patient outcome because they increase both the intrinsic aggressiveness of tumor cells and their resistance to several commonly used anticancer strategies. Pathogenetic mechanisms leading to hypoxia are diverse, may coexist within the same tumor and are commonly grouped according to the duration of their effects. Chronic hypoxia is mainly caused by diffusion limitations resulting from enlarged intercapillary distances and adverse diffusion geometries and — to a lesser extent — by hypoxemia, compromised perfusion or long-lasting microregional flow stops. Conversely, acute hypoxia preferentially results from transient disruptions in perfusion. While each of these features of the tumor microenvironment can contribute to a critical reduction of oxygen availability, the delivery of imaging agents (as well as nutrients and anticancer agents may be compromised or remain unaffected. Thus, a critical appraisal of the effects of the various mechanisms leading to hypoxia with regard to the blood-borne delivery of imaging agents is necessary to judge their ability to correctly represent the hypoxic phenotype of solid malignancies.

  17. Autoradiographic imaging of cerebral ischemia using hypoxic marker: 99mTc-HL91 in animal models

    International Nuclear Information System (INIS)

    Zhu Cansheng; Jiang Ningyi; Hu Xiaoke

    2001-01-01

    Objective: To explore the possibility of 99m Tc-HL91 imaging in detecting the ischemic penumbra during acute stoke. Methods; 16 Sprague-Dawley (SD) rats were divided into operation group (n=12) and pseudo-operation group (n=4) randomly. In operation group, 12 middle cerebral artery occlusion animal (MCAO) models were established by electrocautery. 4 rats in pseudo-operation group were treated as a control without occlusion. All animals were injected 99m Tc-HL91 intravenously 2 hours after occlusion. Animals were killed at different time after injection and brains were removed rapidly from the skull to do the autoradiographic study. Results: The ischemic territory accumulated more 99m Tc-HL91 than the opposite site in the autoradiogram at 1 hour after injection. The ischemic cerebral tissue can be visualized clearly. At 2, 4 hours after injection, the difference of accumulation of 99m Tc-HL91 in target and non-target site became more obvious. By using computer-enhanced imaging analysis, the optical density (OD) ratio differences between each subgroup of operation group and pseudo-operation group were all significant. The OD ratios (T/N) were 1.2691±0.0189, 1.3542±0.0119, 2.1201±0.0616, 2.5369±0.1214 respectively at 1, 2, 4 hours after 99m Tc-HL91 injection. Conclusion: 99m Tc-HL91 can be avidly taken up by ischemic penumbra. 99m Tc-HL91 is a potential agent for imaging hypoxic tissue, and 99m Tc-HL91 SPECT may be a promising imaging method in detecting the ischemic penumbra

  18. Hypoxic-Ischemic Encephalopathy With Clinical and Imaging Abnormalities Limited to Occipital Lobe.

    Science.gov (United States)

    Parmar, Hemant A; Trobe, Jonathan D

    2016-09-01

    The vulnerable brain areas in hypoxic-ischemic encephalopathy (HIE) following systemic hypotension are typically the neocortex, deep cerebral gray nuclei, hippocampus, cerebellum, and the parieto-occipital arterial border zone region. The visual cortex is not commonly recognized as a target in this setting. Single-institution review from 2007 to 2015 of patients who suffered cortical visual loss as an isolated clinical manifestation following systemic hypotension and whose brain imaging showed abnormalities limited to the occipital lobe. Nine patients met inclusion criteria. Visual loss at outset ranged from hand movements to 20/20, but all patients had homonymous field loss at best. In 1 patient, imaging was initially normal but 4 months later showed encephalomalacia. In 2 patients, imaging was initially subtle enough to be recognized as abnormal only when radiologists were advised that cortical visual loss was present. The occipital lobe may be an isolated target in HIE with cortical visual loss as the only clinical manifestation. Imaging performed in the acute period may appear normal or disclose abnormalities subtle enough to be overlooked. Radiologists informed of the clinical manifestations may be more attune to these abnormalities, which will become more apparent months later when occipital volume loss develops.

  19. Role of magnetic resonance imaging in biometric evaluation of corpus callosum in hypoxic ischemic encephalopathy patients

    Directory of Open Access Journals (Sweden)

    Amit Garhwal

    2017-01-01

    Full Text Available Background: Corpus callosum (CC has an important role in establishing hemispheric lateralization of function. Significance of this structure which is the primary white matter commissure of the brain lies in the fact that damage to the CC during development has been found to be associated with poor neurological outcome and neuropsychological performance. Magnetic resonance imaging (MRI can precisely detect, localize, and evaluate damage to CC in hypoxic-ischemic encephalopathy (HIE patients and assist in reaching to at an accurate anatomical diagnosis, thus heeling in further management of the patient. Objectives: The objective of this study is to analyze the effect of HIE on CC morphometry by assessing various diameters of CC. Materials and Methods: Fifty-four patients with history of hypoxic-ischemic injury referred to the Department of Radiodiagnosis were included in the study. All the patients were made to undergo MRI of the brain using Siemens Symphony Magnetom 1.5 Tesla scanner after taking informed consent for the same. The findings of MRI brain were assessed and analyzed. Data analysis was done using percentages of different diagnosis and outcomes made by MRI brain were computed and compiled. Results: In the present study, male predominance is seen, 77.78% patients were male and 22.22% were female. In the present study, maximum numbers of patients were <1 year of age (37.04%. In the present study, we see that the isthmus was the most commonly affected portion of CC. Children who did not cry at birth, born with low birth weight, low Apgar score were positively correlated with severity of damage to CC. Conclusion: From the present study, it was noted that MRI is very efficient tool in evaluating morphometry of CC in HIE. Its noninvasiveness and no exposure to ionizing radiation is an added advantage. However, experience and understanding of the principles are essential for accurate diagnosis.

  20. Stable agents for imaging investigations

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    This invention concerns highly stable compounds useful in preparing technetium 99m based scintiscanning exploration agents. The compounds of this invention include a pertechnetate reducing agent or a solution of oxidized pertechnetate and an efficient proportion, sufficient to stabilize the compounds in the presence of oxygen and of radiolysis products, of ascorbic acid or a pharmaceutically acceptable salt or ester of this acid. The invention also concerns a perfected process for preparing a technetium based exploration agent, consisting in codissolving the ascorbic acid or a pharmaceutically acceptable salt or ester of such an acid and a pertechnetate reducing agent in a solution of oxidized pertechnetate [fr

  1. USE OF DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING FOR REVEALING HYPOXIC-ISCHEMIC BRAIN LESIONS IN NEONATES

    Directory of Open Access Journals (Sweden)

    E. V. Shimchenko

    2014-01-01

    Full Text Available The article presents advantages of use of diffusion-weighted magnetic resonance imaging (DW MRI for revealing hypoxic-ischemic brain lesions in neonates. The trial included 97 neonates with perinatal brain lesion who had been undergoing treatment at a resuscitation department or neonatal pathology department in the first month of life. The article shows high information value of diffusion-weighted images (DWI for diagnostics of hypoxic-ischemic lesions in comparison with regular standard modes. In the event of no structural brain lesions of neonates, pronounced increase in signal characteristics revealed by DWI indicated considerable pathophysiological alterations. Subsequently, children developed structural alterations in the form of cystic encephalomalacia with expansion of cerebrospinal fluid spaces manifested with pronounced neurological deficit. DW MRI has been offered as a method of prognosticating further neurological development of children on early stages. 

  2. Imaging Mass Spectrometry Revealed the Accumulation Characteristics of the 2-Nitroimidazole-Based Agent "Pimonidazole" in Hypoxia.

    Directory of Open Access Journals (Sweden)

    Yukiko Masaki

    Full Text Available Hypoxia, or low oxygen concentration, is a key factor promoting tumor progression and angiogenesis and resistance of cancer to radiotherapy and chemotherapy. 2-Nitroimidazole-based agents have been widely used in pathological and nuclear medicine examinations to detect hypoxic regions in tumors; in particular, pimonidazole is used for histochemical staining of hypoxic regions. It is considered to accumulate in hypoxic cells via covalent binding with macromolecules or by forming reductive metabolites after reduction of its nitro group. However, the detailed mechanism of its accumulation remains unknown. In this study, we investigated the accumulation mechanism of pimonidazole in hypoxic tumor tissues in a mouse model by mass spectrometric analyses including imaging mass spectrometry (IMS. Pimonidazole and its reductive metabolites were observed in the tumor tissues. However, their locations in the tumor sections were not similar to the positively stained areas in pimonidazole-immunohistochemistry, an area considered hypoxic. The glutathione conjugate of reduced pimonidazole, a low-molecular-weight metabolite of pimonidazole, was found in tumor tissues by LC-MS analysis, and our IMS study determined that the intratumor localization of the glutathione conjugate was consistent with the area positively immunostained for pimonidazole. We also found complementary localization of the glutathione conjugate and reduced glutathione (GSH, implying that formation of the glutathione conjugate occurred in the tumor tissue. These results suggest that in hypoxic tumor cells, pimonidazole is reduced at its nitro group, followed by conjugation with GSH.

  3. Doppler imaging of hypoxic-ischemic encephalopathy in term neonates on the first day of life

    International Nuclear Information System (INIS)

    Wilczynska, M.; Stefanczyk, L.; Zieba, K.; Bieganski, T.; Gulczynska, E.

    2004-01-01

    Hypoxic-ischaemic encephalopathy (HIE) is the most important neurological cause of mortality and poor neurodevelopmental outcome in neonates and infants. The aim of the study was to perform routine transfontanellar US brain scanning together with doppler evaluation of blood flow in anterior cerebral artery in the group of neonates with perinatal asphyxia studied at the first day of their life. The study group consisted of asphyxiated neonates (n=11), birth weight 3576,0 ± 426,0 g, gestational age 39,4 ± 1,1 weeks, pH of cord arterial blood 6,89 ± 0,45, 1 st minute Apgar score 2 points. The control group were healthy neonates (n=20), , birth weight 3354,0 ± 378,0 g, gestational age 38,9 ± 1,8 weeks, pH of cord arterial blood 7,28 ± 0,41, 1 st minute Apgar score 8 points. As compared to healthy children asphyxiated neonates had significantly decreased RI value (right cerebral artery 0,53 ± 0,02 vs. 0,72 ± 0,02; left cerebral artery 0,55 ± 0,02 vs. 0,73 ± 0,02), despite not all of them had obvious HIE features in routine US examination. None of these neonates lived longer than 10 days. Doppler examination of cerebral blood flow in term neonates born with perinatal asphyxia could be valuable complementary method of US imaging, especially in those patients with very discreet or absent HIE features in routine US scan. Results of doppler imaging could serve as prognostic factor for clinical outcome. (author)

  4. Contrast Agent in Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Vu-Quang, Hieu

    2015-01-01

    Nanoparticles have been employed as contrast agent in magnetic resonance imaging (MRI) in order to improve sensitivity and accuracy in diagnosis. In addition, these contrast agents are potentially combined with other therapeutic compounds or near infrared bio-imaging (NIR) fluorophores to obtain...... theranostic or dual imaging purposes, respectively. There were two main types of MRI contrast agent that were synthesized during this PhD project including fluorine containing nanoparticles and magnetic nanoparticles. In regard of fluorine containing nanoparticles, there were two types contrast agent...... cancer cells for cancer diagnosis in MRI. F127-Folate coated SPION were stable in various types of suspension medium for over six months. They could specifically target folate receptor of cancer cells in vitro and in vivo thus enhancing the contrast in MRI T2/T2* weighted images. These are preliminary...

  5. Radiolabelling and evaluation of a novel sulfoxide as a PET imaging agent for tumor hypoxia

    International Nuclear Information System (INIS)

    Laurens, Evelyn; Yeoh, Shinn Dee; Rigopoulos, Angela; Cao, Diana; Cartwright, Glenn A.; O'Keefe, Graeme J.; Tochon-Danguy, Henri J.; White, Jonathan M.; Scott, Andrew M.; Ackermann, Uwe

    2014-01-01

    [ 18 F]FMISO is the most widely validated PET radiotracer for imaging hypoxic tissue. However, as a result of the pharmacokinetics of [ 18 F]FMISO a 2 h wait between tracer administration and patient scanning is required for optimal image acquisition. In order to develop hypoxia imaging agents with faster kinetics, we have synthesised and evaluated several F-18 labelled anilino sulfoxides. In this manuscript we report on the synthesis, in vitro and in vivo evaluation of a novel fluoroethyltriazolyl propargyl anilino sulfoxide. The radiolabelling of the novel tracer was achieved via 2-[ 18 F]fluoroethyl azide click chemistry. Radiochemical yields were 23 ± 4% based on 2-[ 18 F]fluoroethyl azide and 7 ± 2% based on K[ 18 F]F. The radiotracer did not undergo metabolism or defluorination in an in vitro assay using S9 liver fractions. Imaging studies using SK-RC-52 tumors in BALB/c nude mice have indicated that the tracer may have a higher pO 2 threshold than [ 18 F]FMISO for uptake in hypoxic tumors. Although clearance from muscle was faster than [ 18 F]FMISO, uptake in hypoxic tumors was slower. The average tumor to muscle ratio at 2 h post injection in large, hypoxic tumors with a volume greater than 686 mm 3 was 1.7, which was similar to the observed ratio of 1.75 for [ 18 F]FMISO. Although the new tracer showed improved pharmacokinetics when compared with the previously synthesised sulfoxides, further modifications to the chemical structure need to be made in order to offer significant in vivo imaging advantages over [ 18 F]FMISO

  6. Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gang, QiangQiang, E-mail: rousikang@163.com; Zhang, Jianing, E-mail: 1325916060@qq.com; Hao, Peng, E-mail: 1043600590@qq.com; Xu, Yikai, E-mail: yikaivip@163.com

    2013-11-01

    Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy.

  7. Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

    International Nuclear Information System (INIS)

    Gang, QiangQiang; Zhang, Jianing; Hao, Peng; Xu, Yikai

    2013-01-01

    Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy

  8. Multimodal nanoparticle imaging agents: design and applications

    Science.gov (United States)

    Burke, Benjamin P.; Cawthorne, Christopher; Archibald, Stephen J.

    2017-10-01

    Molecular imaging, where the location of molecules or nanoscale constructs can be tracked in the body to report on disease or biochemical processes, is rapidly expanding to include combined modality or multimodal imaging. No single imaging technique can offer the optimum combination of properties (e.g. resolution, sensitivity, cost, availability). The rapid technological advances in hardware to scan patients, and software to process and fuse images, are pushing the boundaries of novel medical imaging approaches, and hand-in-hand with this is the requirement for advanced and specific multimodal imaging agents. These agents can be detected using a selection from radioisotope, magnetic resonance and optical imaging, among others. Nanoparticles offer great scope in this area as they lend themselves, via facile modification procedures, to act as multifunctional constructs. They have relevance as therapeutics and drug delivery agents that can be tracked by molecular imaging techniques with the particular development of applications in optically guided surgery and as radiosensitizers. There has been a huge amount of research work to produce nanoconstructs for imaging, and the parameters for successful clinical translation and validation of therapeutic applications are now becoming much better understood. It is an exciting time of progress for these agents as their potential is closer to being realized with translation into the clinic. The coming 5-10 years will be critical, as we will see if the predicted improvement in clinical outcomes becomes a reality. Some of the latest advances in combination modality agents are selected and the progression pathway to clinical trials analysed. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

  9. Liposome imaging agents in personalized medicine

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Hansen, Anders Elias; Gabizon, Alberto

    2012-01-01

    In recent years the importance of molecular and diagnostic imaging has increased dramatically in the treatment planning of many diseases and in particular in cancer therapy. Within nanomedicine there are particularly interesting possibilities for combining imaging and therapy. Engineered liposomes...... that selectively localize in tumor tissue can transport both drugs and imaging agents, which allows for a theranostic approach with great potential in personalized medicine. Radiolabeling of liposomes have for many years been used in preclinical studies for evaluating liposome in vivo performance and has been...... start to consider how to use imaging for patient selection and treatment monitoring in connection to nanocarrier based medicines. Nanocarrier imaging agents could furthermore have interesting properties for disease diagnostics and staging. Here, we review the major advances in the development...

  10. Liposomes as carriers of imaging agents

    International Nuclear Information System (INIS)

    Caride, V.J.

    1985-01-01

    This review discusses the utilization of liposomes as imaging agents or as vehicles for contrast materials. The initial approach was the use of radiolabeled liposomes for scintigraphy. To this end liposomes were either labeled in the lipid membrane or aqueous radiotracers were incorporated inside the lipid vesicles. The lipid labeling provides a more stable association of the radioactive tracer and the lipid vesicles, while the use of water-soluble radiotracers provides a wider selection of compounds. Early attempts at selective tumor imaging using radiolabeled liposomes were unsuccessful. The use of monoclonal antibodies attached to liposomes offers new hopes. Several strategies have been proposed in this respect and several others can be envisioned. The use of liposomes permits the use of several administration routes for imaging agents. Of particular interest is the subcutaneous administration for lymph node visualization. Liposomes offer clear advantages over most radiocontrast agents for prolonged hepatosplenic contrast enhancement. This is particularly relevant in the diagnostic evaluation of the abdomen with computed tomography. Important research efforts are being conducted in this area. Two different approaches have been advanced: the incorporation of contrast agents into liposomes and the preparation of radiopaque liposomes from radiodense lipids. Nuclear magnetic resonance imaging can also benefit from contrast agents. Several centers are investigating this exciting field using liposomes loaded with paramagnetic elements.152 references

  11. Imaging efficacy of a targeted imaging agent for fluorescence endoscopy

    Science.gov (United States)

    Healey, A. J.; Bendiksen, R.; Attramadal, T.; Bjerke, R.; Waagene, S.; Hvoslef, A. M.; Johannesen, E.

    2008-02-01

    Colorectal cancer is a major cause of cancer death. A significant unmet clinical need exists in the area of screening for earlier and more accurate diagnosis and treatment. We have identified a fluorescence imaging agent targeted to an early stage molecular marker for colorectal cancer. The agent is administered intravenously and imaged in a far red imaging channel as an adjunct to white light endoscopy. There is experimental evidence of preclinical proof of mechanism for the agent. In order to assess potential clinical efficacy, imaging was performed with a prototype fluorescence endoscope system designed to produce clinically relevant images. A clinical laparoscope system was modified for fluorescence imaging. The system was optimised for sensitivity. Images were recorded at settings matching those expected with a clinical endoscope implementation (at video frame rate operation). The animal model was comprised of a HCT-15 xenograft tumour expressing the target at concentration levels expected in early stage colorectal cancer. Tumours were grown subcutaneously. The imaging agent was administered intravenously at a dose of 50nmol/kg body weight. The animals were killed 2 hours post administration and prepared for imaging. A 3-4mm diameter, 1.6mm thick slice of viable tumour was placed over the opened colon and imaged with the laparoscope system. A receiver operator characteristic analysis was applied to imaging results. An area under the curve of 0.98 and a sensitivity of 87% [73, 96] and specificity of 100% [93, 100] were obtained.

  12. Smart Contrast Agents for Magnetic Resonance Imaging.

    Science.gov (United States)

    Bonnet, Célia S; Tóth, Éva

    2016-01-01

    By visualizing bioactive molecules or biological parameters in vivo, molecular imaging is searching for information at the molecular level in living organisms. In addition to contributing to earlier and more personalized diagnosis in medicine, it also helps understand and rationalize the molecular factors underlying physiological and pathological processes. In magnetic resonance imaging (MRI), complexes of paramagnetic metal ions, mostly lanthanides, are commonly used to enhance the intrinsic image contrast. They rely either on the relaxation effect of these metal chelates (T(1) agents), or on the phenomenon of paramagnetic chemical exchange saturation transfer (PARACEST agents). In both cases, responsive molecular magnetic resonance imaging probes can be designed to report on various biomarkers of biological interest. In this context, we review recent work in the literature and from our group on responsive T(1) and PARACEST MRI agents for the detection of biogenic metal ions (such as calcium or zinc), enzymatic activities, or neurotransmitter release. These examples illustrate the general strategies that can be applied to create molecular imaging agents with an MRI detectable response to biologically relevant parameters.

  13. Quantification of ante-mortem hypoxic ischemic brain injury by post-mortem cerebral magnetic resonance imaging in neonatal encephalopathy.

    Science.gov (United States)

    Montaldo, Paolo; Chaban, Badr; Lally, Peter J; Sebire, Neil J; Taylor, Andrew M; Thayyil, Sudhin

    2015-11-01

    Post-mortem (PM) magnetic resonance imaging (MRI) is increasingly used as an alternative to conventional autopsy in babies dying from neonatal encephalopathy. However, the confounding effect of post-mortem changes on the detection of ante-mortem ischemic injury is unclear. We examined whether quantitative MR measurements can accurately distinguish ante-mortem ischemic brain injury from artifacts using post-mortem MRI. We compared PM brain MRI (1.5 T Siemens, Avanto) in 7 infants who died with neonatal encephalopathy (NE) of presumed hypoxic-ischemic origin with 7 newborn infants who had sudden unexplained neonatal death (SUND controls) without evidence of hypoxic-ischemic brain injury at autopsy. We measured apparent diffusion coefficients (ADCs), T1-weighted signal intensity ratios (SIRs) compared to vitreous humor and T2 relaxation times from 19 predefined brain areas typically involved in neonatal encephalopathy. There were no differences in mean ADC values, SIRs on T1-weighted images or T2 relaxation times in any of the 19 predefined brain areas between NE and SUND infants. All MRI images showed loss of cortical gray/white matter differentiation, loss of the normal high signal intensity (SI) in the posterior limb of the internal capsule on T1-weighted images, and high white matter SI on T2-weighted images. Normal post-mortem changes may be easily mistaken for ante-mortem ischemic injury, and current PM MRI quantitative assessment cannot reliably distinguish these. These findings may have important implications for appropriate interpretation of PM imaging findings, especially in medico-legal practice. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  14. Azobenzene-caged sulforhodamine dyes: a novel class of ‘turn-on’ reactive probes for hypoxic tumor cell imaging

    Science.gov (United States)

    Chevalier, Arnaud; Piao, Wen; Hanaoka, Kenjiro; Nagano, Tetsuo; Renard, Pierre-Yves; Romieu, Anthony

    2015-12-01

    New sulforhodamine-based fluorescent ‘turn-on’ probes have been developed for the direct imaging of cellular hypoxia. Rapid access to this novel class of water-soluble ‘azobenzene-caged’ fluorophores was made possible through an easily-implementable azo-coupling reaction between a fluorescent primary arylamine derived from a sulforhodamine 101 scaffold (named SR101-NaphtNH 2 ) and a tertiary aniline whose N-substituents are neutral, cationic, or zwitterionic. The detection mechanism is based on the bioreductive cleavage of the azo bond that restores strong far-red fluorescence (emission maximum at 625 nm) by regenerating the original sulforhodamine SR101-NaphtNH 2 . This valuable fluorogenic response was obtained for the three ‘smart’ probes studied in this work, as shown by an in vitro assay using rat liver microsomes placed under aerobic and then under hypoxic conditions. Most importantly, the probe namely SR101-NaphtNH 2 -Hyp-diMe was successfully applied for imaging the hypoxic status of tumor cells (A549 cells).

  15. Contrasts agents in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Bonnet, P.A.; Fernandez, J.P.; Milhavet, J.C.; Chapat, J.P.; Almes, C.; Bruel, J.M.; Rouanet, J.P.; Lamarque, J.L.

    1984-01-01

    Changing different parameters involved in imaging procedures, paramagnetic substances provide contrast enhancement in MRI. Contrast agents presently studied in animals and clinical trials, are either salts or complexes of mineral ions either nitroxide stable free radicals. Their development should extend the possibilities of tissular characterization and fonctional or metabolic evaluation of the MRI [fr

  16. Contrast agents in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Karadjian, V.

    1987-01-01

    The origine of nuclear magnetic resonance signal is reminded and different ways for contrast enhancement in magnetic resonance imaging are presented, especially, modifications of tissus relaxation times. Investigations have focused on development of agents incorporating either paramagnetic ions or stable free radicals. Pharmacological and toxicological aspects are developed. The diagnostic potential of these substances is illustrated by the example of gadolinium complexes [fr

  17. A novel nitroreductase-enhanced MRI contrast agent and its potential application in bacterial imaging

    Directory of Open Access Journals (Sweden)

    Yun Liu

    2018-05-01

    Full Text Available Nitroreductases (NTRs are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide (NADH as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study, para-nitrobenzyl substituted T1-weighted magnetic resonance imaging (MRI contrast agent Gd-DOTA-PNB (probe 1 has been designed and explored for the possible detection of NTR. Our experimental results show that probe 1 could serve as an MRI-enhanced contrast agent for monitoring NTR activity. The in vitro response and mechanism of the NTR catalysed reduction of probe 1 have been investigated through LC–MS and MRI. Para-nitrobenzyl substituted probe 1 was catalytically reduced by NTR to the intermediate para-aminobenzyl substituted probe which then underwent a rearrangement elimination reaction to Gd-DOTA, generating the enhanced T1-weighted MR imaging. Further, LC–MS and MRI studies of living Escherichia coli have confirmed the NTR activity detection ability of probe 1 at a cellular level. This method may potentially be used for the diagnosis of bacterial infections. KEY WORDS: Nitroreductase, MRI contrast agent, Smart imaging probes, Bacterial imaging, Bacterial infection

  18. Modular strategies for PET imaging agents

    International Nuclear Information System (INIS)

    Hooker, J.M.

    2010-01-01

    In recent years, modular and simplified chemical and biological strategies have been developed for the synthesis and implementation of positron emission tomography (PET) radiotracers. New developments in bioconjugation and synthetic methodologies, in combination with advances in macromolecular delivery systems and gene-expression imaging, reflect a need to reduce radiosynthesis burden in order to accelerate imaging agent development. These new approaches, which are often mindful of existing infrastructure and available resources, are anticipated to provide a more approachable entry point for researchers interested in using PET to translate in vitro research to in vivo imaging.

  19. Nanoparticles as image enhancing agents for ultrasonography

    Energy Technology Data Exchange (ETDEWEB)

    Liu Jun [Biomedical Engineering Department, Ohio State University, 270 Bevis Hall, 1080 Carmack Rd, Columbus, OH 43210 (United States); Levine, Andrea L [Department of Veterinary Biosciences, Ohio State University, 1925 Coffey Rd, Columbus, OH 43210 (United States); Mattoon, John S [Department of Veterinary Clinical Sciences, Ohio State University, 1151 Veterinary Hospital, 601 Vernon Tharp St., Columbus, OH 43210 (United States); Yamaguchi, Mamoru [Department of Veterinary Biosciences, Ohio State University, 1925 Coffey Rd, Columbus, OH 43210 (United States); Lee, Robert J [Division of Pharmaceutics, College of Pharmacy, NCI Comprehensive Cancer Center, and NSF Nanoscale Science and Engineering Center, Ohio State University, 500 West 12th Avenue, Columbus, OH 43210 (United States); Pan Xueliang [Department of Statistics, Ohio State University, 1958 Neil Avenue, Columbus, OH 43210 (United States); Rosol, Thomas J [Department of Veterinary Biosciences, Ohio State University, 1925 Coffey Rd, Columbus, OH 43210 (United States)

    2006-05-07

    Nanoparticles have drawn great attention as targeted imaging and/or therapeutic agents. The small size of the nanoparticles allows them to target cells that are beyond capillary vasculature, such as cancer cells. We investigated the effect of solid nanoparticles for enhancing ultrasonic grey scale images in tissue phantoms and mouse livers in vivo. Silica nanospheres (100 nm) were dispersed in agarose at 1-2.5% mass concentration and imaged by a high-resolution ultrasound imaging system (transducer centre frequency: 30 MHz). Polystyrene particles of different sizes (500-3000 nm) and concentrations (0.13-0.75% mass) were similarly dispersed in agarose and imaged. Mice were injected intravenously with nanoparticle suspensions in saline. B-mode images of the livers were acquired at different time points after particle injection. An automated computer program was used to quantify the grey scale changes. Ultrasonic reflections were observed from nanoparticle suspensions in agarose gels. The image brightness, i.e., mean grey scale level, increased with particle size and concentration. The mean grey scale of mouse livers also increased following particle administration. These results indicated that it is feasible to use solid nanoparticles as contrast enhancing agents for ultrasonic imagin000.

  20. Metabolism and pharmacokinetics of the hypoxic cell radiosensitizer and cytotoxic agent, misonidazole, in C3H mice

    International Nuclear Information System (INIS)

    Chin, J.B.; Rauth, A.M.

    1981-01-01

    Misonidazole, a 2-nitroimidazole, is presently of interest because of its radiosensitizing and toxic effects toward hypoxic tumor cells. The plasma and tissue distribution of misonidazole and various products was studied as a function of time and mode of administration in male C3H mice with KHT tumors. Polarographic measurements of nitro-group species in plasma after intravenous or intraperitoneal misonidazole administration indicated apparent half-lives of 1.0 to 1.5 hr. With an oral dose, a multicomponent curve was obtained. [ 14 C]misonidazole, labeled in the 2-position of the imidazole ring, was widely distributed to all tissues tested after intraperitioneal or oral administration. Paper chromatography of plasma and the water-soluble fraction of spleen, liver, kidney, brain, and KHT tumor tissue showed variations in the proportions of misonidazole, its 0-dimethylation product, the aminoimidazole, and low-R/sub F/ products (including glucuronides). There was radioactivity in the gastrointestinal lumen 1 hr after intravenous injection. These studies indicate that differences exist in total drug levels as well as in the proportions of metabolites present in various tissue types. Thus the radiosensitization and toxicity of misonidazole may depend on the particular tissue or tumor under study

  1. The preparation and biological characterization of a new HL91-derivative for hypoxic imaging on stroke mice

    Energy Technology Data Exchange (ETDEWEB)

    Hsia, C.-C. [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taiwan (China); Institute of Nuclear Energy Research, Taiwan (China); Huang, F.-L.; Lin, C.-H.; Shen, L.-H. [Institute of Nuclear Energy Research, Taiwan (China); Wang, H.-E., E-mail: hewang@ym.edu.t [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taiwan (China)

    2010-09-15

    Aim: {sup 99m}Tc-HL91 (Prognox, GE-Healthcare) was the first nonnitro-aryl-based radiotracer for evaluating hypoxic fraction in neoplasm, stroke and myocardium infarction regions. However, the high hydrophilicity of {sup 99m}Tc-HL91 might hamper its penetration into cells. In this study, we prepared a new ligand 4,4,11,11-tetramethyl- 5,10-diazatetradecane- 3,12-dionedioxime (HL91-ET) with higher lipophilicity but structurally similar compared with that of HL91. The chemical and biological characterizations of {sup 99m}Tc-HL91-ET as a scintigraphic probe for hypoxia were performed with a stroke-bearing mouse model. Materials and Methods: HL91-ET was synthesized and formulated with stannous chloride and buffer to afford kits. After mixing with {sup 99m}Tc-pertechnetate, {sup 99m}Tc-HL91-ET can be prepared in high yield and high radiochemical purity (both >96%). The partition coefficient of {sup 99m}Tc-HL91-ET was determined in n-octanol/PBS system. Cellular uptake assays under normoxic and hypoxic conditions were performed in an oxygen-controlled CO{sub 2} incubator. Brain stroke in the mouse model was induced by the electrocautery of the middle cerebral artery. After intravenous injection of {sup 99m}Tc-HL91-ET into the Balb/c mouse suffering brain stroke, small-animal SPECT images were acquired at designated time points and autoradiography of the brain slides was conducted. Parallel studies of {sup 99m}Tc-HL91 were also conducted at the same conditions for comparison. Results: The higher partition coefficient of {sup 99m}Tc-HL91-ET (0.294{+-}0.007) indicated higher lipophlicity compared with that of {sup 99m}Tc-HL91 (0.089{+-}0.005). The {sup 99m}Tc-HL91-ET preparation was stable at ambient temperature for 24 h. Cellular uptake assay showed that {sup 99m}Tc-HL91-ET was less selectively retained in hypoxic cells than {sup 99m}Tc-HL91. The target-to-normal brain ratios derived from the autoradiograms of the brains of stroke mice were 1.31{+-}0.02 and 17

  2. The preparation and biological characterization of a new HL91-derivative for hypoxic imaging on stroke mice

    International Nuclear Information System (INIS)

    Hsia, C.-C.; Huang, F.-L.; Lin, C.-H.; Shen, L.-H.; Wang, H.-E.

    2010-01-01

    Aim: 99m Tc-HL91 (Prognox, GE-Healthcare) was the first nonnitro-aryl-based radiotracer for evaluating hypoxic fraction in neoplasm, stroke and myocardium infarction regions. However, the high hydrophilicity of 99m Tc-HL91 might hamper its penetration into cells. In this study, we prepared a new ligand 4,4,11,11-tetramethyl- 5,10-diazatetradecane- 3,12-dionedioxime (HL91-ET) with higher lipophilicity but structurally similar compared with that of HL91. The chemical and biological characterizations of 99m Tc-HL91-ET as a scintigraphic probe for hypoxia were performed with a stroke-bearing mouse model. Materials and Methods: HL91-ET was synthesized and formulated with stannous chloride and buffer to afford kits. After mixing with 99m Tc-pertechnetate, 99m Tc-HL91-ET can be prepared in high yield and high radiochemical purity (both >96%). The partition coefficient of 99m Tc-HL91-ET was determined in n-octanol/PBS system. Cellular uptake assays under normoxic and hypoxic conditions were performed in an oxygen-controlled CO 2 incubator. Brain stroke in the mouse model was induced by the electrocautery of the middle cerebral artery. After intravenous injection of 99m Tc-HL91-ET into the Balb/c mouse suffering brain stroke, small-animal SPECT images were acquired at designated time points and autoradiography of the brain slides was conducted. Parallel studies of 99m Tc-HL91 were also conducted at the same conditions for comparison. Results: The higher partition coefficient of 99m Tc-HL91-ET (0.294±0.007) indicated higher lipophlicity compared with that of 99m Tc-HL91 (0.089±0.005). The 99m Tc-HL91-ET preparation was stable at ambient temperature for 24 h. Cellular uptake assay showed that 99m Tc-HL91-ET was less selectively retained in hypoxic cells than 99m Tc-HL91. The target-to-normal brain ratios derived from the autoradiograms of the brains of stroke mice were 1.31±0.02 and 17.47±0.10 (n=3), respectively, at 2 h post injection of 99m Tc-HL91-ET and 99m Tc-HL91

  3. Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging.

    Science.gov (United States)

    Daryaei, Iman; Pagel, Mark D

    2015-01-01

    Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.

  4. New avenues in hypoxic cell sensitization

    International Nuclear Information System (INIS)

    Huilgol, N.G.; Chatterjee, N.A.; Singh, B.B.

    1995-01-01

    Hypoxic cells in tumors represent a population of cells that are resistant to radiotherapy. Bio-reductive agents like RSU 1069, RBU 6145 and EOg and vasoactive drugs in conjunction with hypoxic cell sensitizers are being evaluated as hypoxic cell cytotoxins. Chlorpromazine a membrane active drug and AK-2123- a nitrotriazole with a potential to deplete intracellular thiols induced vasoconstriction and sensitize hypoxic cells have stretched the boundaries of innovation. A preliminary experience with these drugs is discussed. 8 refs., 2 tabs., 2 figs

  5. Comparison of several potential myocardial imaging agents

    International Nuclear Information System (INIS)

    Watson, E.E.; Stabin, M.G.; Goodman, M.M.; Knapp, F.F. Jr.; Srivastava, P.C.

    1985-01-01

    Although myocardial imaging is currently dominated by Tl-201, several alternative agents with improved physiologic or radionuclidic properties have been proposed. Based on human and animal studies in the literature, the metabolism of several of these compounds was studied for the purpose of generating radiation dose estimates. Dose estimates are listed for several I-123 labeled free fatty acids, an I-123 labeled phosphonium compound, Rb-82, Cu-64, F-18 FDG (all compounds which are taken up by the normal myocardium), and for Tc-99m pyrophosphate (PYP) (which localizes in myocardial infarcts). Dose estimates could not be generated for C-11 palmitate, but this compound was included in a comparison of myocardial retention times. For the I-123 labeled compounds, I-124 was included as a contaminant in generating the dose estimates. Radiation doses were lowest for Rb-82 (gonads 0.3 to 0.5 μGy/MBq, heart wall 15 μGy/MBq). Doses for the I-123 labeled fatty acids were similar to one another, with IPPA being the lowest (gonads 20 μGy/MBq, heart wall 15 μGy/MBq). Doses for Tc-99m PYP were also low (gonads 4 to 7 μGy/MBq, heart wall 4 μGy/MBq, skeleton 15 μGy/MBq). The desirability of these compounds is discussed briefly, considering half life, imaging mode and energy, and dosimetry, including a comparison of the effective whole body dose equivalents. 34 refs., 11 tabs

  6. Magnetic Resonance Imaging Contrast Agents: A Review of Literature

    Directory of Open Access Journals (Sweden)

    Zahra Sahraei

    2015-10-01

    Full Text Available  Magnetic Resonance Imaging (MRI contrast agents most commonly agents used in diagnosing different diseases. Several agents have been ever introduced with different peculiar characteristics. They vary in potency, adverse reaction and other specification, so it is important to select the proper agent in different situations. We conducted a systematic literature search in MEDLINE/PUBMED, Web of Science (ISI, Scopus,Google Scholar by using keywords "gadolinium" and "MRI contrast Medias", "Gadofosvest", "Gadobenate" and "Gadoxetate". The most frequent contrast media agents made based on gadolinium (Gd. These are divided into two categories based on the structure of their chelating parts, linear agents and macrocyclic agents. All characteristics of contrast media factors, including efficiency, kinetic properties, stability, side effects and the rate of resolution are directly related to the structure of chelating part of that formulation.In vitro data has shown that the macrocyclic compounds are the most stable Gd-CA as they do not bind to serum proteins, they all possess similar and relatively low relaxivity and the prevalence of Nephrogenic Systemic Fibrosis (NSF has decreased by increasing the use of macrocyclic agents in recent years. No cases of NSF have been recorded after the administration of any of the high-relaxivity protein interacting agents, the vascular imaging agent gadofosveset trisodium (Ablavar, the hepatic imaging agent gadoxetate meglumine (Eovist, and the multipurpose agent gadobenate dimeglumine (MultiHance. In pregnancy and lactating women, stable macrocyclic agent is recommended.

  7. Intelligent Design of Nano-Scale Molecular Imaging Agents

    Directory of Open Access Journals (Sweden)

    Takeaki Ozawa

    2012-12-01

    Full Text Available Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs, biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on–off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents.

  8. Radiolabelled spiroperidol: Possible pituitary adenoma imaging agent

    International Nuclear Information System (INIS)

    Otto, C.A.; Marshall, J.C.; Lloyd, R.V.; Sherman, P.S.; Wieland, D.M.

    1984-01-01

    Prolactin-secreting pituitary adenomas are the most common type of pituitary tumors. Detection currently depends on physical symptoms, elevated serum prolactin levels and CT scans. An imaging agent which specifically localized in prolactinomas based on some functional characteristic of the tumor would be of considerable clinical value not only for early detection but also for monitoring of therapy. Tritiated spiroperidol ( 3 H-Sp) was selected for evaluation based on 1) the presence of D-2 receptors in normal anterior pituitary and adenoma tissue and 2) the high affinity of spiroperidol for D-2 receptors. Recent data have established that implantation of diethylstilbestrol (DES) in Fischer F344 rats induced prolactin-secreting tumors in the pituitary. 3 HSp was evaluated in pituitary tissue of both control and DES-treated rats. 3 HSp concentration in normal female anterior pituitary tissue was found to be about 0.27% kg dose/g from 5 min to 4hrs. This value was about 10 times levels in cortex, cerebellum and striatum. In DES-treated rats the % kg dose/g values remained approximately the same. A 5-fold increase in serum prolactin was associated with a 6-fold increase in both pituitary weight and % dose/organ. The data suggests that although total pituitary weight has increased due to tumor growth (reflected in increased values for % dose/organ), the relative number of receptors per g of tissue has remained constant. This result is in agreement with observations of others on D-2 receptor concentration in prolactinomas

  9. MR imaging of term infants with hypoxic-ischaemic encephalopathy as a predictor of neurodevelopmental outcome and late MRI appearances

    International Nuclear Information System (INIS)

    Twomey, Eilish; Ryan, Stephanie; Twomey, Anne; Murphy, John; Donoghue, Veronica B.

    2010-01-01

    Morbidity attributable to hypoxic-ischaemic injury (HIE) in the perinatal period remains problematic, and timely and accurate assessment of the degree of injury is required for clinical management and prognosis. Conventional MR sequences typically appear normal in the first 48 h post HIE. While diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps register the injury earlier, perhaps within the first 24 h, it has been suggested that there may be a propensity at that early stage to underestimate the lesion severity or extent. To assess whether MR imaging that included DWI, measured ADC values and T1- and T2-weighted sequences ultimately correlated with either neurodevelopmental outcome or with late MR imaging at 2 years of age. In addition, we wished to compare the performance of MR imaging with cranial US imaging. All infants presenting with HIE who had an MRI within 10 days of life were eligible for enrollment and subsequently underwent a full neurodevelopmental assessment at 2 years of age. All children underwent repeat MRI at this time. All neonates had at least one cranial US study. The US findings were categorized as normal, abnormalities confined to the cerebral cortex and subcortical white matter, isolated central grey matter hyperechogenicity, and central hyperechogenicity combined with cerebral cortical/subcortical changes. All MRI studies were retrospectively reviewed by three radiologists. The patterns of injury on the early DWI and ADC maps and early T1- and T2-W studies were recorded as diffuse, central, watershed or atypical. The patterns of signal abnormality were assessed using a scoring system that yielded four separate scores [basal ganglia (BG), watershed (W), BG/W and summation (S)] for the three sets of images, a total of 12 scores in all. The appearance of the posterior limb of the internal capsule (PLIC) on T1-W inversion recovery sequences and of the corpus callosum on all sequences was also documented. After

  10. MR imaging of term infants with hypoxic-ischaemic encephalopathy as a predictor of neurodevelopmental outcome and late MRI appearances

    Energy Technology Data Exchange (ETDEWEB)

    Twomey, Eilish; Ryan, Stephanie [Children' s University Hospital, Department of Radiology, Dublin (Ireland); Twomey, Anne; Murphy, John [National Maternity Hospital, Department of Neonatology, Dublin (Ireland); Donoghue, Veronica B. [National Maternity Hospital, Department of Radiology, Dublin (Ireland); Children' s University Hospital, Department of Radiology, Dublin (Ireland)

    2010-09-15

    Morbidity attributable to hypoxic-ischaemic injury (HIE) in the perinatal period remains problematic, and timely and accurate assessment of the degree of injury is required for clinical management and prognosis. Conventional MR sequences typically appear normal in the first 48 h post HIE. While diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps register the injury earlier, perhaps within the first 24 h, it has been suggested that there may be a propensity at that early stage to underestimate the lesion severity or extent. To assess whether MR imaging that included DWI, measured ADC values and T1- and T2-weighted sequences ultimately correlated with either neurodevelopmental outcome or with late MR imaging at 2 years of age. In addition, we wished to compare the performance of MR imaging with cranial US imaging. All infants presenting with HIE who had an MRI within 10 days of life were eligible for enrollment and subsequently underwent a full neurodevelopmental assessment at 2 years of age. All children underwent repeat MRI at this time. All neonates had at least one cranial US study. The US findings were categorized as normal, abnormalities confined to the cerebral cortex and subcortical white matter, isolated central grey matter hyperechogenicity, and central hyperechogenicity combined with cerebral cortical/subcortical changes. All MRI studies were retrospectively reviewed by three radiologists. The patterns of injury on the early DWI and ADC maps and early T1- and T2-W studies were recorded as diffuse, central, watershed or atypical. The patterns of signal abnormality were assessed using a scoring system that yielded four separate scores [basal ganglia (BG), watershed (W), BG/W and summation (S)] for the three sets of images, a total of 12 scores in all. The appearance of the posterior limb of the internal capsule (PLIC) on T1-W inversion recovery sequences and of the corpus callosum on all sequences was also documented. After

  11. PET/CT imaging of striatal dopamine transporters in a newborn piglet model of hypoxic-ischemic brain injury

    International Nuclear Information System (INIS)

    Zhang Yanfen; Wang Xiaoming; Wang Xiaoyu; Cao Li; Guo Qiyong

    2013-01-01

    Objective: To investigate changes of striatal DAT following hypoxic ischemic (HI) brain injury in newborn piglets using 11 C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (CFT) PET/CT, and to evaluate the value of 11 C-CFT PET/CT in brain injury. Methods: Newborn piglets with HI brain injury (n=20) were taken as a model group,and five piglets were used as a control group. Radioligand 11 C-CFT (55.5-74.0 MBq) was injected through the jugular vein, and PET/CT imaging was performed to observe the changes of striatal DAT in newborn piglets. The ST/occipital lobe (OC) ratio was calculated. Model group was divided into 0-6 h, 20-24 h, 44-48 h and 68-72 h sub-groups after HI in accordance with the imaging time. The piglets were sacrificed immediately after 11 C-CFT PET/CT scanning, and then the brains were removed for pathological analysis. Data analysis was performed with one-way analysis of variance and Pearson linear correlation analysis. Results: After intravenous injection of 11 C-CFT, the radioactivity accumulation in cortical, striatum, and cerebellum was shown clearly in the control and model groups. The radioactivity accumulation was lower in the white matter. The radioactivity in cortical and cerebellum exhibited decreased with time, while the striatum was still clear. After HI, the ST/OC activity ratio in the striatum was initially increased, and the ratio of 0-6 h group (1.34 ± 0.04) was statistically significant compared with that of the control group (1.18 ± 0.06; F=4.658, P<0.05), followed by a gradual decrease. ST/OC ratios of other HI subgroups were 1.27 ±0.01, 1.27 ±0.10 and 1.18 ±0.05, respectively. There was a positive correlation between the number of DAT positive neurons ((13 ± 3), (13 ± 4), (8 ±3) and (4 ±4)/high power field) and 11 C-CFT ST/OC activity ratios (r=0.844, P<0.05). Conclusion: 11 C-CFT PET/CT study can accurately reflect the changes of DAT in the striatum, and the amount of DAT is related to the severity of the ischemic insult

  12. Fundamental study of DSA images using gadolinium contrast agent

    International Nuclear Information System (INIS)

    Nagashima, Hiroyuki; Shiraishi, Akihisa; Igarashi, Hitoshi; Sakamoto, Hajime; Sano, Yoshitomo

    2002-01-01

    Most contrast agents used in digital subtraction angiography (DSA) are non-ionic iodinated contrast agents, which can cause severe side effects in patients with contraindications for iodine or allergic reactions to iodine. Therefore, DSA examinations using carbon dioxide gas or examinations done by magnetic resonance imaging (MRI) and ultrasound (US) were carried out in these patients. However, none of these examinations provided mages as clear as those of DSA with an iodinated contrast agent. We experienced DSA examination using a gadolinium contrast agent in a patient contraindicated for iodine. The patient had undergone MRI examination with a gadolinium contrast agent previously without side effects. The characteristics of gadolinium and the iodinated contrast agent were compared, and the DSA images obtained clinically using these media were also evaluated. The signal-to-noise (SN) ratio of the gadolinium contrast agent was the highest at tube voltages of 70 to 80 kilovolts and improved slightly when the image intensifier (I.I.) entrance dose was greater than 300 μR (77.4 nC/kg). The dilution ratios of five iodinated contrast agents showed the same S/N value as the undiluted gadolinium contrast agent. Clinically, the images obtained showed a slight decrease in contrast but provided the data necessary to make a diagnosis and made it possible to obtain interventional radiology (IVR) without any side effects. DSA examinations using a gadolinium contrast agent have some benefit with low risk and are thought to be useful for patients contraindicated for iodine. (author)

  13. Use of hypoxia imaging agent 99mTc-HL91 in rat cerebral ischemia models

    International Nuclear Information System (INIS)

    Zhou Ying; Qu Wanying; Li Meng; Chen Fang; Yao Zhiming; Zhu Ming; Zhu Lin

    1999-01-01

    Objective: To explore the possibility of diagnosis for cerebrovascular disease by a novel synthetic hypoxia agent 99m Tc-HL91 used in rat cerebral ischemia models. Methods: Pharmacological experiments of 99m Tc-HL91 were carried out including common properties, radiochemical purity, stability in vitro, anomalous toxicity test and biodistribution in mice. Fifteen cerebral ischemic rat models were established and received 99m Tc-HL91 scintigraphy. Results: 1) HL91 kits were labelled with 99m Tc easily and showed high radiochemical purity and stability. 2) Rapid clearance in blood, heart and lungs and high activity in liver, kidneys and intestines were observed. Relatively low uptake in brain was identified. 3) The radioactivity in ischemic brain tissue increased significantly at 4h postinjection in both rat images and isolated brain images. 4) The radioactivity ratios of lesion to normal brain tissue by drawing ROIs in isolated brain planar images were 0.98 +- 0.06, 0.99 +- 0.05, 1.29 +- 0.03, 1.56 +- 0.14 and 1.66 +- 0.06 at 1,2,4,8 and 12 h postinjection, respectively. There were significant differences among all groups except for 1 h and 2 h, 8 h and 12 h postinjection (P 99m Tc-HL91 in the hypoxic, ischemic brain tissue have been proved. It is appropriate to perform imaging at 4 h postinjection

  14. Magnetic resonance imaging contrast agents: Overview and perspectives

    International Nuclear Information System (INIS)

    Yan Guoping; Robinson, Leslie; Hogg, Peter

    2007-01-01

    Magnetic resonance imaging (MRI) is a non-invasive clinical imaging modality, which has become widely used in the diagnosis and/or staging of human diseases around the world. Some MRI examinations include the use of contrast agents. The categorizations of currently available contrast agents have been described according to their effect on the image, magnetic behavior and biodistribution in the body, respectively. In this field, superparamagnetic iron oxide particles and soluble paramagnetic metal chelates are two main classes of contrast agents for MRI. This review outlines the research and development of MRI contrast agents. In future, the ideal MRI contrast agent will be focused on the neutral tissue- or organ-targeting materials with high relaxivity and specificity, low toxicity and side effects, suitable long intravascular duration and excretion time, high contrast enhancement with low dose in vivo, and with minimal cost

  15. Development of a Multifaceted Ovarian Cancer Therapeutic and Imaging Agent

    National Research Council Canada - National Science Library

    Markland, Francis S

    2008-01-01

    ...%. This project outlines the development of a recombinant version of a member of a class of proteins known as disintegrins as an innovative imaging and diagnostic agent for ovarian cancer (OC). Vicrostatin (VN...

  16. Quinone-fused porphyrins as contrast agents for photoacoustic imaging

    KAUST Repository

    Banala, Srinivas; Fokong, Stanley; Brand, Christian; Andreou, Chrysafis; Krä utler, Bernhard; Rueping, Magnus; Kiessling, Fabian

    2017-01-01

    Photoacoustic (PA) imaging is an emerging non-invasive diagnostic modality with many potential clinical applications in oncology, rheumatology and the cardiovascular field. For this purpose, there is a high demand for exogenous contrast agents

  17. Modified natural nanoparticles as contrast agents for medical imaging

    NARCIS (Netherlands)

    Cormode, David P.; Jarzyna, Peter A.; Mulder, Willem J. M.; Fayad, Zahi A.

    2010-01-01

    The development of novel and effective contrast agents is one of the drivers of the ongoing improvement in medical imaging. Many of the new agents reported are nanoparticle-based. There are a variety of natural nanoparticles known, e.g. lipoproteins, viruses or ferritin. Natural nanoparticles have

  18. Improved radionuclide bone imaging agent injection needle withdrawal method can improve image quality

    International Nuclear Information System (INIS)

    Qin Yongmei; Wang Laihao; Zhao Lihua; Guo Xiaogang; Kong Qingfeng

    2009-01-01

    Objective: To investigate the improvement of radionuclide bone imaging agent injection needle withdrawal method on whole body bone scan image quality. Methods: Elbow vein injection syringe needle directly into the bone imaging agent in the routine group of 117 cases, with a cotton swab needle injection method for the rapid pull out the needle puncture point pressing, pressing moment. Improvement of 117 cases of needle injection method to put two needles into the skin swabs and blood vessels, pull out the needle while pressing two or more entry point 5min. After 2 hours underwent whole body bone SPECT imaging plane. Results: The conventional group at the injection site imaging agents uptake rate was 16.24%, improved group was 2.56%. Conclusion: The modified bone imaging agent injection needle withdrawal method, injection-site imaging agent uptake were significantly decreased whole body bone imaging can improve image quality. (authors)

  19. Cardiac image segmentation for contrast agent videodensitometry

    NARCIS (Netherlands)

    Mischi, M.; Kalker, A.A.C.M.; Korsten, H.H.M.

    2005-01-01

    Indicator dilution techniques are widely used in the intensive care unit and operating room for cardiac parameter measurements. However, the invasiveness of current techniques represents a limitation for their clinical use. The development of stable ultrasound contrast agents allows new applications

  20. Evaluation of potential gastrointestinal contrast agents for echoplanar MR imaging

    International Nuclear Information System (INIS)

    Reimer, P.; Schmitt, F.; Ladebeck, R.; Graessner, J.; Schaffer, B.

    1993-01-01

    The purpose of this study was to investigate approved aqueous gastrointestinal contrast agents for use in abdominal EPI. Conventional and echoplanar MR imaging experiments were performed with 1.0 Tesla whole body systems. Phantom measurements of Gastrografin, barium sulfate suspension, oral gadopentetate dimeglumine, water, and saline were performed. Signal intensity (SI) of aqueous oral barium sulfate and iodine based CT contrast agents was lower on conventional spin-echo (SE), Flash, and Turbo-Flush images than on EP images. The contrast agents exhibited higher SI on T2-weighted SE PE images and TI-time dependence on inversion recovery EP-images. The barium sulfate suspension was administered in volunteers to obtain information about bowel lumen enhancement and susceptibility artifacts. Oral administration of the aqueous barium sulfate suspension increased bowel lumen signal and reduced susceptibility artifacts. (orig.)

  1. 64Cu loaded liposomes as positron emission tomography imaging agents

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Binderup, Tina; Rasmussen, Palle

    2011-01-01

    applicable as PET imaging agents. We show the utility of the 64Cu-liposomes for quantitative in vivo imaging of healthy and tumor-bearing mice using PET. This remote loading method is a powerful tool for characterizing the in vivo performance of liposome based nanomedicine, and has great potential...

  2. Nanogels as imaging agents for modalities spanning the electromagnetic spectrum.

    Science.gov (United States)

    Chan, Minnie; Almutairi, Adah

    2016-01-21

    In the past few decades, advances in imaging equipment and protocols have expanded the role of imaging in in vivo diagnosis and disease management, especially in cancer. Traditional imaging agents have rapid clearance and low specificity for disease detection. To improve accuracy in disease identification, localization and assessment, novel nanomaterials are frequently explored as imaging agents to achieve high detection specificity and sensitivity. A promising material for this purpose are hydrogel nanoparticles, whose high hydrophilicity, biocompatibility, and tunable size in the nanometer range make them ideal for imaging. These nanogels (10 to 200 nm) can circumvent uptake by the reticuloendothelial system, allowing longer circulation times than small molecules. In addition, their size/surface properties can be further tailored to optimize their pharmacokinetics for imaging of a particular disease. Herein, we provide a comprehensive review of nanogels as imaging agents in various modalities with sources of signal spanning the electromagnetic spectrum, including MRI, NIR, UV-vis, and PET. Many materials and formulation methods will be reviewed to highlight the versatility of nanogels as imaging agents.

  3. Advanced Contrast Agents for Multimodal Biomedical Imaging Based on Nanotechnology.

    Science.gov (United States)

    Calle, Daniel; Ballesteros, Paloma; Cerdán, Sebastián

    2018-01-01

    Clinical imaging modalities have reached a prominent role in medical diagnosis and patient management in the last decades. Different image methodologies as Positron Emission Tomography, Single Photon Emission Tomography, X-Rays, or Magnetic Resonance Imaging are in continuous evolution to satisfy the increasing demands of current medical diagnosis. Progress in these methodologies has been favored by the parallel development of increasingly more powerful contrast agents. These are molecules that enhance the intrinsic contrast of the images in the tissues where they accumulate, revealing noninvasively the presence of characteristic molecular targets or differential physiopathological microenvironments. The contrast agent field is currently moving to improve the performance of these molecules by incorporating the advantages that modern nanotechnology offers. These include, mainly, the possibilities to combine imaging and therapeutic capabilities over the same theranostic platform or improve the targeting efficiency in vivo by molecular engineering of the nanostructures. In this review, we provide an introduction to multimodal imaging methods in biomedicine, the sub-nanometric imaging agents previously used and the development of advanced multimodal and theranostic imaging agents based in nanotechnology. We conclude providing some illustrative examples from our own laboratories, including recent progress in theranostic formulations of magnetoliposomes containing ω-3 poly-unsaturated fatty acids to treat inflammatory diseases, or the use of stealth liposomes engineered with a pH-sensitive nanovalve to release their cargo specifically in the acidic extracellular pH microenvironment of tumors.

  4. Photoacoustic imaging at 1064nm wavelength with exogenous contrast agents

    Science.gov (United States)

    Upputuri, Paul Kumar; Jiang, Yuyan; Pu, Kanyi; Pramanik, Manojit

    2018-02-01

    Photoacoustic (PA) imaging is a promising imaging modality for both preclinical research and clinical practices. Laser wavelengths in the first near infrared window (NIR-I, 650-950 nm) have been widely used for photoacoustic imaging. As compared with NIR-I window, scattering of photons by biological tissues is largely reduced in the second NIR (NIR-II) window, leading to enhanced imaging fidelity. However, the lack of biocompatible NIR-II absorbing exogenous agents prevented the use of this window for in vivo imaging. In recent years, few studies have been reported on photoacoustic imaging in NIR-II window using exogenous contrast agents. In this work, we discuss the recent work on PA imaging using 1064 nm wavelength, the fundamental of Nd:YAG laser, as an excitation wavelength. The PA imaging at 1064 nm is advantageous because of the low and homogeneous signal from tissue background, enabling high contrast in PA imaging when NIR-II absorbing contrast agents are employed.

  5. Electroencephalogram and magnetic resonance imaging comparison as a predicting factor for neurodevelopmental outcome in hypoxic ischemic encephalopathy infant treated with hypothermia

    Directory of Open Access Journals (Sweden)

    Francesca Del Balzo

    2014-10-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is an important cause of acute neurological damage in newborns at (or near term. Several trials in recent years have shown that moderate hypothermia by total body cooling or selective head is an effective intervention to reduce mortality and major disability in infants survived a perinatal hypoxic-ischemic attack. Follow-up in these patients is very important to establish neurodevelopmental outcome, and specific markers can lead us to detect predicting sign for good or poor outcome. We reported a few cases of newborn with HIE treated with hypothermia, in whom the comparison between electroencephalogram (EEG and magnetic resonance imaging (MRI represents the first marker for neurodevelopment outcome prediction. The continuous EEG monitoring showed a depressed EEG activity with diffuse burst depression in 7 patients. No epileptic abnormalities were registered. In 10 out of 20 patients no abnormalities of the background activity and no epileptic abnormalities were observed. We found that a depressed EEG activity during the first 72 h of life and a diffused alteration of basal ganglia at MRI were correlated with a poor neurodevelopmental outcome at 18 months of follow-up.

  6. Gadolinium-based contrast agents in pediatric magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gale, Eric M.; Caravan, Peter [Massachusetts General Hospital, Harvard Medical School, Department of Radiology, The Martinos Center for Biomedical Imaging, Boston, MA (United States); Rao, Anil G. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); McDonald, Robert J. [College of Medicine, Mayo Clinic, Department of Radiology, Rochester, MN (United States); Winfeld, Matthew [University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (United States); Fleck, Robert J. [Cincinnati Children' s Hospital Medical Center, Department of Pediatric Radiology, Cincinnati, OH (United States); Gee, Michael S. [MassGeneral Hospital for Children, Harvard Medical School, Division of Pediatric Imaging, Department of Radiology, Boston, MA (United States)

    2017-05-15

    Gadolinium-based contrast agents can increase the accuracy and expediency of an MRI examination. However the benefits of a contrast-enhanced scan must be carefully weighed against the well-documented risks associated with administration of exogenous contrast media. The purpose of this review is to discuss commercially available gadolinium-based contrast agents (GBCAs) in the context of pediatric radiology. We discuss the chemistry, regulatory status, safety and clinical applications, with particular emphasis on imaging of the blood vessels, heart, hepatobiliary tree and central nervous system. We also discuss non-GBCA MRI contrast agents that are less frequently used or not commercially available. (orig.)

  7. The clinical use of contrast agents in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Bydder, G.M.

    1987-01-01

    Interest in the use of external agents to increase tissue contrasts has come from many sources dating back to the earliest work in NMR, to animal studies and to the widespread use of contrast agents in conventional radiological practice. The first clinical magnetic resonance images were published in 1980 and in the following year a brief account of the use of the paramagnetic agents in human volunteers was established. It was apparent relatively early in the development of magnetic resonance imaging (MRI) that a high level of soft tissue contrast was available de novo and the need for externally administered agents might therefore be small. This observation was tempered by the fact that separation of tumour from oedema was frequently better with contrast enhanced CT X-ray than with unenhanced MRI and that of a contrast agent might therefore be needed for MRI. At the end of 1983 the first parenteral agent gadoliminum diethylene triamine pentaacetic acid (Gd-DTPA) was used in volunteers and clinical studies began in 1984. At the present time only molecular O/sub 2/, oral iron compounds and Gd-DTPA are in clinical use although there are a number of other agents which have been used in animals and some of these may become available for clinical use in the foreseeable future

  8. Fluorescence Imaging/Agents in Tumor Resection.

    Science.gov (United States)

    Stummer, Walter; Suero Molina, Eric

    2017-10-01

    Intraoperative fluorescence imaging allows real-time identification of diseased tissue during surgery without being influenced by brain shift and surgery interruption. 5-Aminolevulinic acid, useful for malignant gliomas and other tumors, is the most broadly explored compound approved for fluorescence-guided resection. Intravenous fluorescein sodium has recently received attention, highlighting tumor tissue based on extravasation at the blood-brain barrier (defective in many brain tumors). Fluorescein in perfused brain, unselective extravasation in brain perturbed by surgery, and propagation with edema are concerns. Fluorescein is not approved but targeted fluorochromes with affinity to brain tumor cells, in development, may offer future advantages. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Preclinical assessment of hypoxic marker specificity and sensitivity

    International Nuclear Information System (INIS)

    Iyer, Renuka V.; Engelhardt, Edward L.; Stobbe, Corinne C.; Schneider, Richard F.; Chapman, J. Donald

    1998-01-01

    Purpose: In the search for a sensitive, accurate, and noninvasive technique for quantifying human tumor hypoxia, our laboratory has synthesized several potential radiodiagnostic agents. The purpose of this study was to assess and compare the hypoxic marking properties of both radioiodinated and Tc-99m labeled markers in appropriate test systems which can predict for in vivo activity. Materials and Methods: Preclinical assessment of hypoxic marker specificity and sensitivity employed three laboratory assays with tumor cells in vitro and in vivo. Radiolabeled marker uptake and/or binding to whole EMT-6 tumor cells under extremely hypoxic and aerobic conditions was measured and their ratio defined hypoxia-specific factor (HSF). Marker specificity to hypoxic tumor tissue was estimated from its selective avidity to two rodent tumors in vivo, whose radiobiologic hypoxic fractions (HF) had been measured. The ratios of % injected dose/gram (%ID/g) of marker at various times in EMT-6 tumor tissue relative to that in the blood and muscle of scid mice were used to quantify hypoxia-specific activity. This tumor in this host exhibited an average radiobiologic HF of ∼35%. As well, nuclear medicine images were acquired from R3327-AT (HF ≅15%) and R3327-H (no measurable HF) prostate carcinomas growing in rats to distinguish between marker avidity due to hypoxia versus perfusion. Results: The HSF for FC-103 and other iodinated markers were higher (5-40) than those for FC-306 and other Tc-99m labeled markers. The latter did not show hypoxia-specific uptake into cells in vitro. Qualitative differences were observed in the biodistribution and clearance kinetics of the iodinated azomycin nucleosides relative to the technetium chelates. The largest tumor/blood (T/B) and tumor/muscle (T/M) ratios were observed for compounds of the azomycin nucleoside class in EMT-6 tumor-bearing scid mice. These markers also showed a 3-4 x higher uptake into R3327-AT tumors relative to the well

  10. Viscous optical clearing agent for in vivo optical imaging

    Science.gov (United States)

    Deng, Zijian; Jing, Lijia; Wu, Ning; lv, Pengyu; Jiang, Xiaoyun; Ren, Qiushi; Li, Changhui

    2014-07-01

    By allowing more photons to reach deeper tissue, the optical clearing agent (OCA) has gained increasing attention in various optical imaging modalities. However, commonly used OCAs have high fluidity, limiting their applications in in vivo studies with oblique, uneven, or moving surfaces. In this work, we reported an OCA with high viscosity. We measured the properties of this viscous OCA, and tested its successful performances in the imaging of a living animal's skin with two optical imaging modalities: photoacoustic microscopy and optical coherence tomography. Our results demonstrated that the viscous OCA has a great potential in the study of different turbid tissues using various optical imaging modalities.

  11. The Correlation Between a Short-term Conventional Electroencephalography in the First Day of Life and Brain Magnetic Resonance Imaging in Newborns Undergoing Hypothermia for Hypoxic-Ischemic Encephalopathy.

    Science.gov (United States)

    Obeid, Rawad; Sogawa, Yoshimi; Gedela, Satyanarayana; Naik, Monica; Lee, Vince; Telesco, Richard; Wisnowski, Jessica; Magill, Christine; Painter, Michael J; Panigrahy, Ashok

    2017-02-01

    Electroencephalograph recorded in the first day of life in newborns treated with hypothermia for hypoxic-ischemic encephalopathy could be utilized as a predictive tool for the severity of brain injury on magnetic resonance imaging and mortality. We analyzed newborns who were admitted for therapeutic hypothermia due to hypoxic-ischemic encephalopathy. All enrolled infants underwent encephalography within the first 24 hours of life and underwent brain magnetic resonance imaging after rewarming. All encephalographs were independently reviewed for background amplitude, continuity, and variability. Brain injury determined by magnetic resonance imaging was scored using methods described by Bonifacio et al. Forty-one newborns were included in the study. Each encephalograph variable correlated significantly with the severity of injury on brain magnetic resonance imaging (P encephalopathy correlated with the extent of injury on brain magnetic resonance imaging. This information may be useful for families and aid guide clinical decision making. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. New strategy of cancer therapy by targeting the hypoxic circumstances

    International Nuclear Information System (INIS)

    Yasui, Hironobu; Yamamori, Tohru; Meike, Shunsuke; Eitaki, Masato; Kuwabara, Mikinori; Inanami, Osamu; Iizuka, Daisuke

    2010-01-01

    Described are studies on the sensitization of tumor cells in hypoxic circumstances (known as radio-resistant cells) by authors' recent molecular targeting to adaptive response as well as by the usual agents like nitro-imidazole compounds, and on the intermittent hypoxia, a new topic in this field. The hypoxia-inducible factor-1 (HIF-1) is a transcriptional factor and has been known to activate its many downstream genes to cause adoptive response of hypoxic cells. Authors have studied the anti-tumor and radiation sensitizing effects of ethynyl-cytidine (EC) which is found to suppress RNA synthesis through cytidine kinase (CK) inhibition, and the compound is of specificity to tumor cells as they have 5-10 times higher CK activity than normal cells. Authors have also found that EC is of the sensitizing efficacy to normoxic and hypoxic cells by enhancing the radiation-induced apoptosis essentially through inhibition of HIF-1 expression. Intermittent hypoxia in the tumor which has characteristic abnormal vascular morphology and function, occurs by the transient reduction of blood flow and occlusion of vessels in the tissue within minute to hour time cycles. Little is known about the regional hypoxic region and its distribution in the tumor due to difficulty of their detection and quantification. For this, authors have measured the temporal changes of oxygen levels in the mouse tumor with triaryl methyl radical, an oxygen-sensitive contrast compound continuously injected, by microwave-pulsed electron spin resonance imaging (EPRI). By superimposing the EPRI and T2-weighted MRI, the oxymetric imaging is possible in the tumor, which reveals the difference of oxygen level variation depending on the cell type and tissue size. Findings in the field are expected to give important information for more effective cancer therapy and its prognostic prediction in future. (T.T.)

  13. A comparison of positron-emitting blood pool imaging agents

    International Nuclear Information System (INIS)

    Hnatowich, D.J.; Kulprathipanja, S.; Evans, G.; Elmaleh, D.

    1979-01-01

    The three agents, 11 C-carboxyhaemoglobin, 68 Ga-transferrin and 68 Ga-labelled red cells have been compared in dogs to assess their relative merits for blood-pool imaging. For 1 h following administration of each agent, periodic blood samples were withdrawn for counting in a NaI (Tl) well counter while conventional two-dimensional images were obtained simultaneously on the Massachusetts General Hospital positron camera. Count rates in regions about the heart, liver and spleen were obtained for each image. The disappearance of blood activity as shown from the results of counting the blood samples and from the counting rates in regions about the heart was found to be identical within experimental error for the three agents. In the liver and spleen regions, the highest count rates were obtained with 68 Ga-transferrin and the lowest with 68 Ga-labelled red cells; count rates in these regions with labelled red cells were virtually constant throughout the 1 h study. It may be concluded that with the exceptions noted above, the three agents are approximately equivalent for blood-pool imaging. (author)

  14. Dynamic fluorescence imaging with molecular agents for cancer detection

    Science.gov (United States)

    Kwon, Sun Kuk

    Non-invasive dynamic optical imaging of small animals requires the development of a novel fluorescence imaging modality. Herein, fluorescence imaging is demonstrated with sub-second camera integration times using agents specifically targeted to disease markers, enabling rapid detection of cancerous regions. The continuous-wave fluorescence imaging acquires data with an intensified or an electron-multiplying charge-coupled device. The work presented in this dissertation (i) assessed dose-dependent uptake using dynamic fluorescence imaging and pharmacokinetic (PK) models, (ii) evaluated disease marker availability in two different xenograft tumors, (iii) compared the impact of autofluorescence in fluorescence imaging of near-infrared (NIR) vs. red light excitable fluorescent contrast agents, (iv) demonstrated dual-wavelength fluorescence imaging of angiogenic vessels and lymphatics associated with a xenograft tumor model, and (v) examined dynamic multi-wavelength, whole-body fluorescence imaging with two different fluorescent contrast agents. PK analysis showed that the uptake of Cy5.5-c(KRGDf) in xenograft tumor regions linearly increased with doses of Cy5.5-c(KRGDf) up to 1.5 nmol/mouse. Above 1.5 nmol/mouse, the uptake did not increase with doses, suggesting receptor saturation. Target to background ratio (TBR) and PK analysis for two different tumor cell lines showed that while Kaposi's sarcoma (KS1767) exhibited early and rapid uptake of Cy5.5-c(KRGDf), human melanoma tumors (M21) had non-significant TBR differences and early uptake rates similar to the contralateral normal tissue regions. The differences may be due to different compartment location of the target. A comparison of fluorescence imaging with NIR vs. red light excitable fluorescent dyes demonstrates that NIR dyes are associated with less background signal, enabling rapid tumor detection. In contrast, animals injected with red light excitable fluorescent dyes showed high autofluorescence. Dual

  15. Radiolabelling and evaluation of novel haloethylsulfoxides as PET imaging agents for tumor hypoxia

    International Nuclear Information System (INIS)

    Laurens, Evelyn; Yeoh, Shinn Dee; Rigopoulos, Angela; Cao, Diana; Cartwright, Glenn A.; O'Keefe, Graeme J.; Tochon-Danguy, Henri J.; White, Jonathan M.; Scott, Andrew M.; Ackermann, Uwe

    2012-01-01

    The significance of imaging hypoxia with the PET ligand [ 18 F]FMISO has been demonstrated in a variety of cancers. However, the slow kinetics of [ 18 F]FMISO require a 2-h delay between tracer administration and patient scanning. Labelled chloroethyl sulfoxides have shown faster kinetics and higher contrast than [ 18 F]FMISO in a rat model of ischemic stroke. However, these nitrogen mustard analogues are unsuitable for routine production and use in humans. Here we report on the synthesis and in vitro and in vivo evaluation of two novel sulfoxides which we synthesised from a single precursor molecule via either 2-[ 18 F]fluoroethyl azide click chemistry or conventional nucleophilic displacement of a chloride leaving group. The yields of the click chemistry approach were 90±5% of [ 18 F] based on 2-[ 18 F]fluoroethyl azide, and the yields for the S N reaction were 15±5% of [ 18 F] based on K[ 18 F]F. Both radiotracers underwent metabolism in an in vitro assay using S9 liver fractions with biological half-lives of 32.39 and 43.32 min, respectively. Imaging studies using an SK-RC-52 tumor model in BALB/c nude mice have revealed that only [ 18 F] is retained in hypoxic tumors, whereas [ 18 F] is cleared from those tumors at a rate similar to that of muscle tissue. [ 18 F] has emerged as a promising new lead structure for further development of sulfoxide-based hypoxia imaging agents. In particular, the mechanism of uptake needs to be elucidated and changes to the chemical structure need to be made in order to reduce metabolism and improve radiotracer kinetics.

  16. Technetium SPECT agents for imaging heart and brain

    International Nuclear Information System (INIS)

    Linder, K.E.

    1990-01-01

    One major goal of radiopharmaceutical research has been the development of technetium-based perfusion tracers for SPECT imaging of the heart and brain. The recent clinical introduction of the technetium complexes HM-PAO, ECD and DMG-2MP for brain imaging, and of CDO-MEB and MIBI for heart imaging promises to revolutionize the field of nuclear medicine. All of these agents appear to localize in the target tissue in proportion to blood flow, but their mechanisms of localization and/or retention may differ quite widely. In this talk, a survey of the new technetium SPECT agents will be presented. The inorganic and biological chemistry of these complexes, mechanisms of uptake and retention, QSAR studies, and potential clinical applications are discussed

  17. Paramagnetic metal complexes as potential relaxation agents for NMR imaging

    International Nuclear Information System (INIS)

    Coroiu, Ilioara; Demco, D. E.; Darabont, Al.; Bogdan, M.

    1997-01-01

    The development of nuclear magnetic resonance (NMR) imaging technique as a clinical diagnostic modality has prompted the need for a new class of pharmaceuticals. These drugs must be administered to a patient in order to enhance the image contrast between the normal and diseased tissue and/or indicate the status of organ function or blood flow. Paramagnetic compounds are presently undergoing extensive evaluation as contrast agents in magnetic resonance imaging (MRI). These agents increase contrast in MRI by differentially localizing in tissue where they increase the relaxation rates of nearby water protons. The longitudinal R 1 and transverse R 2 relaxivities were measured as a function of molar concentrations for some new paramagnetic complexes like the following: dysprosium, erbium and gadolinium citrates, gadolinium methylene diphosphonate, dysprosium and gadolinium iminodiacetate, manganese para-aminobenzoate and copper nicotinate. The available theoretical approaches for quantitative understanding are presented. (authors)

  18. Cellular image segmentation using n-agent cooperative game theory

    Science.gov (United States)

    Dimock, Ian B.; Wan, Justin W. L.

    2016-03-01

    Image segmentation is an important problem in computer vision and has significant applications in the segmentation of cellular images. Many different imaging techniques exist and produce a variety of image properties which pose difficulties to image segmentation routines. Bright-field images are particularly challenging because of the non-uniform shape of the cells, the low contrast between cells and background, and imaging artifacts such as halos and broken edges. Classical segmentation techniques often produce poor results on these challenging images. Previous attempts at bright-field imaging are often limited in scope to the images that they segment. In this paper, we introduce a new algorithm for automatically segmenting cellular images. The algorithm incorporates two game theoretic models which allow each pixel to act as an independent agent with the goal of selecting their best labelling strategy. In the non-cooperative model, the pixels choose strategies greedily based only on local information. In the cooperative model, the pixels can form coalitions, which select labelling strategies that benefit the entire group. Combining these two models produces a method which allows the pixels to balance both local and global information when selecting their label. With the addition of k-means and active contour techniques for initialization and post-processing purposes, we achieve a robust segmentation routine. The algorithm is applied to several cell image datasets including bright-field images, fluorescent images and simulated images. Experiments show that the algorithm produces good segmentation results across the variety of datasets which differ in cell density, cell shape, contrast, and noise levels.

  19. Magnetic nanoparticles as contrast agents for molecular imaging in medicine

    Science.gov (United States)

    O'Donnell, Matthew

    2018-05-01

    For over twenty years, superparamagnetic nanoparticles have been developed for a number of medical applications ranging from bioseparations, magnetic drug targeting, hyperthermia and imaging. Recent studies have shown that they can be functionalized for in vivo biological targeting, potentially enabling nanoagents for molecular imaging and site-localized drug delivery. Here we review several imaging technologies developed using functionalized superparamagnetic iron oxide nanoparticles (SPIONs) as targeted molecular agents. Several imaging modalities have exploited the large induced magnetic moment of SPIONs to create local mechanical force. Magnetic force microscopy can probe nanoparticle uptake in single cells. For in vivo applications, magnetomotive modulation of primary images in ultrasound (US), photoacoustics (PA), and optical coherence tomography (OCT) can help identify very small concentrations of nanoagents while simultaneously suppressing intrinsic background signals from tissue.

  20. Microscopic validation of whole mouse micro-metastatic tumor imaging agents using cryo-imaging and sliding organ image registration

    OpenAIRE

    Liu, Yiqiao; Zhou, Bo; Qutaish, Mohammed; Wilson, David L.

    2016-01-01

    We created a metastasis imaging, analysis platform consisting of software and multi-spectral cryo-imaging system suitable for evaluating emerging imaging agents targeting micro-metastatic tumor. We analyzed CREKA-Gd in MRI, followed by cryo-imaging which repeatedly sectioned and tiled microscope images of the tissue block face, providing anatomical bright field and molecular fluorescence, enabling 3D microscopic imaging of the entire mouse with single metastatic cell sensitivity. To register ...

  1. Development of (F-18)-Labeled Amyloid Imaging Agents for PET

    International Nuclear Information System (INIS)

    Mathis, C.A.

    2007-01-01

    The applicant proposes to design and synthesize a series of fluorine-18-labeled radiopharmaceuticals to be used as amyloid imaging agents for positron emission tomography (PET). The investigators will conduct comprehensive iterative in vitro and in vivo studies based upon well defined acceptance criteria in order to identify lead agents suitable for human studies. The long term goals are to apply the selected radiotracers as potential diagnostic agents of Alzheimer's disease (AD), as surrogate markers of amyloid in the brain to determine the efficacy of anti-amyloid therapeutic drugs, and as tools to help address basic scientific questions regarding the progression of the neuropathology of AD, such as testing the 'amyloid cascade hypothesis' which holds that amyloid accumulation is the primary cause of AD.

  2. In vivo imaging agents: an international market report

    International Nuclear Information System (INIS)

    1990-01-01

    The purpose of this study is to provide a global perspective of the in vivo imaging agents business to market planning executives who are working for companies that develop, produce and distribute various types of in vivo imaging agents. Others that could find this study useful include investment bankers, regulatory and governmental authorities and purchasers of these products. The study attempts to diligently provide market data by type for important geographic markets - Western Europe, the U.S.A., and Japan. A competitive intelligence section which discusses companies involved in these markets constitutes the last part of this study. These profiles are not intended to extensively evaluate each company's marketing strengths or strategies but to provide a general idea of the market presence and prospects. A combination of primary and secondary research is used for all findings. (author)

  3. Novel MR imaging contrast agents for cancer detection

    Directory of Open Access Journals (Sweden)

    Daryoush Shahbazi-Gahrouei

    2009-05-01

    Full Text Available

    • BACKGROUND: Novel potential MR imaging contrast agents Gd-tetra-carboranylmethoxyphenyl-porphyrin (Gd-TCP, Gd-hematoporphyrin (Gd-H, Gd-DTPA-9.2.27 against melanoma, Gd-DTPA-WM53 against leukemia and Gd-DTPAC595 against breast cancer cells were synthesized and applied to mice with different human cancer cells (melanoma MM-138, leukemia HL-60, breast MCF-7. The relaxivity, the biodistribution, T1 relaxation times, and signal enhancement of the contrast agents are presented and the results are compared.
    • METHODS: After preparation of contrast agents, the animal studies were performed. The cells (2×106 cells were injected subcutaneously in the both flanks of mice. Two to three weeks after tumor plantation, when the tumor diameter was 2-4 mm, mice were injected with the different contrast agents. The animals were sacrificed at 24 hr post IP injection followed by removal of critical organs. The T1 relaxation times and signal intensities of samples were measured using 11.4 T magnetic field and Gd concentration were measured using UV-spectrophotometer.
    • RESULTS: For Gd-H, the percent of Gd localized to the tumors measured by UV-spect was 28, 23 and 21 in leukemia, melanoma and breast cells, respectively. For Gd-TCP this amount was 21%, 18% and 15%, respectively. For Gd-DTPA-9.2.27, Gd-DTPA-WM53 and Gd-DTPA-C595 approximately 35%, 32% and 27% of gadolinium localized to their specific tumor, respectively.
    • CONCLUSION: The specific studied conjugates showed good tumor uptake in the relevant cell lines and low levels of Gd in the liver, kidney and spleen. The studied agents have considerable promise for further diagnosis applications of MR imaging.
    • KEYWORDS: Magnetic Resonance, Imaging, Monoclonal Antibody, Contrast Agents, Gadolinium, Early Detection of Cancer.

  4. Quinone-fused porphyrins as contrast agents for photoacoustic imaging

    KAUST Repository

    Banala, Srinivas

    2017-06-27

    Photoacoustic (PA) imaging is an emerging non-invasive diagnostic modality with many potential clinical applications in oncology, rheumatology and the cardiovascular field. For this purpose, there is a high demand for exogenous contrast agents with high absorption coefficients in the optical window for tissue imaging, i.e. the near infrared (NIR) range between 680 and 950 nm. We herein report the photoacoustic properties of quinone-fused porphyrins inserted with different transition metals as new highly promising candidates. These dyes exhibit intense NIR absorption, a lack of fluorescence emission, and PA sensitivity in concentrations below 3 nmol mL. In this context, the highest PA signal was obtained with a Zn(ii) inserted dye. Furthermore, this dye was stable in blood serum and free thiol solution and exhibited negligible cell toxicity. Additionally, the Zn(ii) probe could be detected with an up to 3.2 fold higher PA intensity compared to the clinically most commonly used PA agent, ICG. Thus, further exploration of the \\'quinone-fusing\\' approach to other chromophores may be an efficient way to generate highly potent PA agents that do not fluoresce and shift their absorption into the NIR range.

  5. Application of I-123 HIPDM as a lung imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Shih, W J; Coupal, J J; Dillon, M L; Kung, H F

    1988-04-01

    N,N,N'-Trimethyl-N'-(2-Hydroxyl-3-Methyl-5-/sup 123/I Iodobenzyl)-1,3-Propanediamine.Hcl (/sup 123/I-HIPDM) has been used for diagnosis of patients with strokes and demantias. Since this radiopharmaceutical is also accumulated in the lung, we routinely performed a lung image or images immediately prior to cerebral planar and SPECT images after a 3-5 mCi /sup 123/I-HIPDM injection. During the past 14 months, we obtained 78 (age from 41 to 92 years, average 66.7+-8.9 years; 64 males, 14 females) suspected stroke or dementia patients' lung images. All lung images were correlated to chest X-ray (CXR) or CT and other clinical data. Sixty five of 78 patients had normal lungs showing homogeneous distribution of activity throughout the lungs which correlated well to normal CXR and/or CT studies. Abnormal scintigraphic patterns of the 13 patients included lung defect (5 bronchogenic carcinoma with or without atelectasis) and decreased uptake in apices (8 chronic obstructive pulmonary disease). The findings of pulmonary intrathoracic pathologies on lung images with /sup 123/I-HIPDM suggests further evaluation of the agent for detection of localized pulmonary diseases and pulmonary physiological studies relating to amine metabolism.

  6. AAZTA: an ideal chelating agent for the development of {sup 44}Sc PET imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Gabor; Szikra, Dezso; Trencsenyi, Gyoergy [Scanomed Ltd., Debrecen (Hungary); University of Debrecen, Medical Imaging Clinic (Hungary); Fekete, Aniko [University of Debrecen, Medical Imaging Clinic (Hungary); Garai, Ildiko [Scanomed Ltd., Debrecen (Hungary); Giani, Arianna M.; Negri, Roberto [Dipartimento di Scienze del Farmaco, Universita del Piemonte Orientale, Novara (Italy); Masciocchi, Norberto [Dipartimento di Scienza e Alta Tecnologia e To.Sca.Lab, Universita degli Studi dell' Insubria, Como (Italy); Maiocchi, Alessandro; Uggeri, Fulvio [Bracco Imaging spa, Bracco Research Centre, Colleretto Giacosa (Italy); Toth, Imre [Department of Inorganic and Analytical Chemistry, University of Debrecen (Hungary); Aime, Silvio [Dipartimento di Biotecnologie Molecolari e Scienze della Salute, Centro di Imaging Molecolare e Preclinico, Universita degli Studi di Torino (Italy); Giovenzana, Giovanni B. [Dipartimento di Scienze del Farmaco, Universita del Piemonte Orientale, Novara (Italy); CAGE Chemicals srl, Novara (Italy); Baranyai, Zsolt [Bracco Imaging spa, Bracco Research Centre, Colleretto Giacosa (Italy); Department of Inorganic and Analytical Chemistry, University of Debrecen (Hungary)

    2017-02-13

    Unprecedented fast and efficient complexation of Sc{sup III} was demonstrated with the chelating agent AAZTA (AAZTA=1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)] amino-6-methylperhydro-1,4-d iazepine) under mild experimental conditions. The robustness of the {sup 44}Sc(AAZTA){sup -} chelate and conjugated biomolecules thereof is further shown by in vivo PET imaging in healthy and tumor mice models. The new results pave the way towards development of efficient Sc-based radiopharmaceuticals using the AAZTA chelator. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  7. The use of contrast agent for imaging biological samples

    Energy Technology Data Exchange (ETDEWEB)

    Dammer, J; Sopko, V; Jakubek, J [Institute of Experimental and Applied Physics, Czech Technical University in Prague, Horska 3a/22, CZ 12800 Prague 2 (Czech Republic); Weyda, F, E-mail: jiri.dammer@utef.cvut.cz [Biological center of the Academy of Sciences of the Czech Republic, Institute of Entomology, Branisovska 31, CZ-37005 Ceske Budejovice (Czech Republic)

    2011-01-15

    The technique of X-ray transmission imaging has been available for over a century and is still among the fastest and easiest approaches to the studies of internal structure of biological samples. Recent advances in semiconductor technology have led to the development of new types of X-ray detectors with direct conversion of interacting X-ray photon to an electric signal. Semiconductor pixel detectors seem to be specially promising; compared to the film technique, they provide single-quantum and real-time digital information about the objects being studied. We describe the recently developed radiographic apparatus, equipped with Medipix2 semiconductor pixel detector. The detector is used as an imager that counts individual photons of ionizing radiation, emitted by an X-ray tube (micro- or nano-focus FeinFocus). Thanks to the wide dynamic range of the Medipix2 detector and its high spatial resolution better than 1{mu}m, the setup is particularly suitable for radiographic imaging of small biological samples, including in-vivo observations with contrast agent (Optiray). Along with the description of the apparatus we provide examples of the use iodine contrast agent as a tracer in various insects as model organisms. The motivation of our work is to develop our imaging techniques as non-destructive and non-invasive. Microradiographic imaging helps detect organisms living in a not visible environment, visualize the internal biological processes and also to resolve the details of their body (morphology). Tiny live insects are an ideal object for our studies.

  8. Liver nodules. MR imaging using extracellular gadolinium agent

    International Nuclear Information System (INIS)

    Yoshimitsu, Kengo; Honda, Hiroshi

    2009-01-01

    Extracellular gadolinium (Gd)-containing contrast medium, including gadopentetate dimeglumine (Gd-DTPA), has been playing a main role in the diagnostic MR imaging of the liver. Its significance is two-fold: assessment of the degree of neovascularity or angiogenesis in its early dynamic phase, and that of bulk of interstitium in its equilibrium phase. With the advent of gadolinium ethoxybenzyl diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA), which can be used as a dynamic study agent by bolus injection in addition to its original use as a tissue-specific agent, some possibility has been suggested that extracellular Gd agent would be no longer available in the near future in the field of liver MR imaging. Neovascularity or arterial supply of a lesion may well be assessed by Gd-EOB-DTPA, when carefully selected pulse sequence and well designed injection protocol are used, as well as by Gd-DTPA. However, the pertinent assessment of interstitium or stroma can never be achieved by Gd-EOB-DTPA or any other contrast medium present. The interstitium of neoplasm, typically called as stromal fibrosis, is generated through the interaction between the neoplasm per se and its host, and its clinicopathological significance related to disease prognosis has well been established in some disease entities. Extracellular Gd agent is the only contrast medium that can provide information regarding the tumor stroma in a simple, easy, safe and non-invasive fashion, when properly used. This review article discusses, dynamic MR imaging features of representative liver diseases, including several recent topics. From technical point of view, 3D gradient-echo sequence with fat suppression should be used for dynamic studies along with tailored injection protocol using autoinjector and saline flush. Vascularity of hepatocellular carcinoma (HCC) can now be properly assessed by dynamic MR with approximately 90% concordance with CT during hepatic arteriography. Portal phase images can be used to

  9. Detecting Vascular-Targeting Effects of the Hypoxic Cytotoxin Tirapazamine in Tumor Xenografts Using Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Bains, Lauren J.; Baker, Jennifer; Kyle, Alastair H.; Minchinton, Andrew I.; Reinsberg, Stefan A.

    2009-01-01

    Purpose: To determine whether vascular-targeting effects can be detected in vivo using magnetic resonance imaging (MRI). Methods and Materials: MR images of HCT-116 xenograft-bearing mice were acquired at 7 Tesla before and 24 hours after intraperitoneal injections of tirapazamine. Quantitative dynamic contrast-enhanced MRI analyses were performed to evaluate changes in tumor perfusion using two biomarkers: the volume transfer constant (K trans ) and the initial area under the concentration-time curve (IAUC). We used novel implanted fiducial markers to obtain cryosections that corresponded to MR image planes from excised tumors; quantitative immunohistochemical mapping of tumor vasculature, perfusion, and necrosis enabled correlative analysis between these and MR images. Results: Conventional histological analysis showed lower vascular perfusion or greater amounts of necrosis in the central regions of five of eight tirapazamine-treated tumors, with three treated tumors showing no vascular dysfunction response. MRI data reflected this result, and a striking decrease in both K trans and IAUC values was seen with the responsive tumors. Retrospective evaluation of pretreatment MRI parameters revealed that those tumors that did not respond to the vascular-targeting effects of tirapazamine had significantly higher pretreatment K trans and IAUC values. Conclusions: MRI-derived parameter maps showed good agreement with histological tumor mapping. MRI was found to be an effective tool for noninvasively monitoring and predicting tirapazamine-mediated central vascular dysfunction.

  10. Magnetic susceptibility imaging with a nonionic contrast agent

    International Nuclear Information System (INIS)

    Cacheris, W.; Rocklage, S.M.; Quay, S.; Dow, W.; Love, D.; Worah, D.; Lim, K.

    1988-01-01

    The magnetic susceptibility mechanism for MR imaging contrast enhancement has the advantage of providing useful information, such as cerebral blood flow, without crossing the blood-brain barrier. In this paper the authors report the use of a highly effective, relatively nontoxic chelate as a magnetic susceptibility agent. Dy-DTPA-bis(methylamide) (Dy-DTPA-BMA) has an extremely low acute toxicity (LD-50, intravenous, mice ∼ 40 mmol/kg). Doses of 1 mmol/kg and 2 mmol/kg Dy-DTPA-BMA lowered the initial signal intensity 63% to 57%, respectively. The utility of this technique in detecting areas of reduced blood flow within the brain was demonstrated by imaging a rabbit with a cerebral perfusion deficit

  11. The preparation and characterization of peptide's lung cancer imaging agent

    International Nuclear Information System (INIS)

    Liu Jianfeng; Chu Liping; Wang Yan; Wang Yueying; Liu Jinjian; Wu Hongying

    2010-01-01

    Objective: To screen in vivo lung cancer specific binding seven peptides by T7 phage display peptide library, so as to prepare peptide's lung cancer early diagnostic agent. Methods: Use phage display in vivo technology, the 7-peptide phage that binding the lung cancer specifically was obtained, then the DNA sequence was measured and the seven peptide was synthesized. After labeled by 125 I, the seven peptide was injected into mice via vein and the distribution was observed. Results: One peptide was obtained by four rounds screening, and the peptide can bind lung cancer tissue specifically. Two hours after injection get the best imaging of lung cancer, metabolism of peptide in mice is fast, the distribution in vivo is decrease six hours and almost disappear 20 hours after injection. Conclusion: The peptide can image and diagnose lung cancer better. (authors)

  12. Nitroimidazoles and imaging hypoxia

    International Nuclear Information System (INIS)

    Nunn, A.; Linder, K.; Strauss, H.W.

    1995-01-01

    A class of compounds known to undergo different intracellular metabolism depending on the availability of oxygen in tissue, the nitroimidazoles, have been advocated for imaging hypoxic tissue. In the presence of normal oxygen levels the molecule is immediately reoxidized. In hypoxic tissue the low oxygen concentration is not able to effectively compete to reoxidize the molecule and further reduction appears to take place. The association is not irreversible. Nitroimidazoles for in vivo imaging using radiohalogenated derivatives of misonidazole have recently been employed in patients. Two major problems with fluoromisonidazole are its relatively low concentration within the lesion and the need to wait several hours to permit clearance of the agent from the normoxic background tissue. Even with high-resolution positron emission tomographic imaging, this combination of circumstances makes successful evaluation of hypoxic lesions a challenge. Single-photon agents, with their longer half-lives and comparable biological properties, offer a greater opportunity for successful imaging. In 1992 technetium-99m labeled nitroimidazoles were described that seem to have at least comparable in vivo characteristics. Laboratory studies have demonstrated preferential binding of these agents to hypoxic tissue in the myocardium, in the brain, and in tumors. These investigations indicate that imaging can provide direct evidence of tissue with low oxygen levels that is viable. Even from this early vantage point the utility of measuring tissue oxygen levels with external imaging suggests that hypoxia imaging could play a major role in clinical decision making. (orig./MG)

  13. Nicotinic α4β2 receptor imaging agents

    International Nuclear Information System (INIS)

    Pichika, Rama; Easwaramoorthy, Balasubramaniam; Collins, Daphne; Christian, Bradley T.; Shi, Bingzhi; Narayanan, Tanjore K.; Potkin, Steven G.; Mukherjee, Jogeshwar

    2006-01-01

    The α4β2 nicotinic acetylcholine receptor (nAChR) has been implicated in various neurodegenerative diseases. Optimal positron emission tomography (PET) imaging agents are therefore highly desired for this receptor. We report here the development and initial evaluation of 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (nifene). In vitro binding affinity of nifene in rat brain homogenate using 3 H-cytisine exhibited a K i =0.50 nM for the α4β2 sites. The radiosynthesis of 2- 18 F-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ( 18 F-nifene) was accomplished in 2.5 h with an overall radiochemical yield of 40-50%, decay corrected. The specific activity was estimated to be approx. 37-185 GBq/μmol. In vitro autoradiography in rat brain slices indicated selective binding of 18 F-nifene to anteroventral thalamic (AVT) nucleus, thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. Rat cerebellum showed some binding, whereas regions in the hippocampus had the lowest binding. The highest ratio of >13 between AVT and cerebellum was measured for 18 F-nifene in rat brain slices. The specific binding was reduced (>95%) by 300 μM nicotine in these brain regions. Positron emission tomography imaging study of 18 F-nifene (130 MBq) in anesthetized rhesus monkey was carried out using an ECAT EXACT HR+ scanner. PET study showed selective maximal uptake in the regions of the anterior medial thalamus, ventro-lateral thalamus, lateral geniculate, cingulate gyrus, temporal cortex including the subiculum. The cerebellum in the monkeys showed lower binding than the other regions. Thalamus-to-cerebellum ratio peaked at 30-35 min postinjection to a value of 2.2 and subsequently reduced. The faster binding profile of 18 F-nifene indicates promise as a PET imaging agent and thus needs further evaluation

  14. Shape Effects in Nanoparticle-Based Imaging Agents

    Science.gov (United States)

    Culver, Kayla Shani Brook

    At the nanoscale, material properties become highly size and shape dependent. These properties can be manipulated and exploited for a variety of biomedical applications, including sensing, drug delivery, diagnostics, and imaging. In particular, nanoparticles of different materials, sizes and shapes have been developed as high-performance contrast agents for optical, electron, and medical imaging. In this thesis, I focus on gold nanoparticles because they are widely used as contrast agents in multiple types of imaging modalities. Additionally, the surface of gold can be readily functionalized with ligands and the structure of the particles can be manipulated to modulate their performance as imaging agents. The properties of nanoparticles can generate contrast directly. For example, the light scattering properties of gold particles can be visualized in optical microscopy, the high electron density of gold produces contrast in electron microscopy, and the x-ray absorption properties of gold can be detected in medical x-ray and computed tomography imaging. Alternatively, the properties of the nanomaterial can be exploited to modulate the signal produced by other molecules that are bound to the particle surface. The light emission of molecular fluorophores can be quenched or dramatically increased by coupling to the optical field enhancements of gold nanoparticles, and the performance of gadolinium (Gd(III))-based magnetic resonance imaging (MRI) contrast agents can be increased by coupling to the rotational motion of nanoparticles. In this dissertation, I focus specifically on how the structure of star-shaped gold particles (nanostars) can be exploited as single-particle optical probes and to dramatically enhance the relaxivity of Gd(III) bound to the surface. Differential interference contrast (DIC) is a type of wide-field diffraction-limited optical microscopy that is commonly used by biologists to image cells without labels. Here, I demonstrate the DIC can be used

  15. Gadolinium chloride as a contrast agent for imaging wood composite components by magnetic resonance

    Science.gov (United States)

    Thomas L. Eberhardt; Chi-Leung So; Andrea Protti; Po-Wah So

    2009-01-01

    Although paramagnetic contrast agents have an established track record in medical uses of magnetic resonance imaging (MRI), only recently has a contrast agent been used for enhancing MRI images of solid wood specimens. Expanding on this concept, wood veneers were treated with a gadolinium-based contrast agent and used in a model system comprising three-ply plywood...

  16. Prognostic value of diffusion-weighted imaging summation scores or apparent diffusion coefficient maps in newborns with hypoxic-ischemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Cavalleri, Francesca; Todeschini, Alessandra [Azienda Unita Sanitaria Locale di Modena, Neuroradiology Unit, Department of Neuroscience, Nuovo Ospedale Civile S. Agostino Estense di Modena, Modena (Italy); Lugli, Licia; Pugliese, Marisa; Della Casa, Elisa; Gallo, Claudio; Frassoldati, Rossella; Ferrari, Fabrizio [Modena University Hospital, Institute of Pediatrics and Neonatal Medicine and NICU, Modena (Italy); D' Amico, Roberto [University of Modena and Reggio Emilia, Department of Clinical and Diagnostic Medicine and Public Health, Modena (Italy)

    2014-09-15

    The diagnostic and prognostic assessment of newborn infants with hypoxic-ischemic encephalopathy (HIE) comprises, among other tools, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps. To compare the ability of DWI and ADC maps in newborns with HIE to predict the neurodevelopmental outcome at 2 years of age. Thirty-four term newborns with HIE admitted to the Neonatal Intensive Care Unit of Modena University Hospital from 2004 to 2008 were consecutively enrolled in the study. All newborns received EEG, conventional MRI and DWI within the first week of life. DWI was analyzed by means of summation (S) score and regional ADC measurements. Neurodevelopmental outcome was assessed with a standard 1-4 scale and the Griffiths Mental Developmental Scales - Revised (GMDS-R). When the outcome was evaluated with a standard 1-4 scale, the DWI S scores showed very high area under the curve (AUC) (0.89) whereas regional ADC measurements in specific subregions had relatively modest predictive value. The lentiform nucleus was the region with the highest AUC (0.78). When GMDS-R were considered, DWI S scores were good to excellent predictors for some GMDS-R subscales. The predictive value of ADC measurements was both region- and subscale-specific. In particular, ADC measurements in some regions (basal ganglia, white matter or rolandic cortex) were excellent predictors for specific GMDS-R with AUCs up to 0.93. DWI S scores showed the highest prognostic value for the neurological outcome at 2 years of age. Regional ADC measurements in specific subregions proved to be highly prognostic for specific neurodevelopmental outcomes. (orig.)

  17. Prognostic value of diffusion-weighted imaging summation scores or apparent diffusion coefficient maps in newborns with hypoxic-ischemic encephalopathy

    International Nuclear Information System (INIS)

    Cavalleri, Francesca; Todeschini, Alessandra; Lugli, Licia; Pugliese, Marisa; Della Casa, Elisa; Gallo, Claudio; Frassoldati, Rossella; Ferrari, Fabrizio; D'Amico, Roberto

    2014-01-01

    The diagnostic and prognostic assessment of newborn infants with hypoxic-ischemic encephalopathy (HIE) comprises, among other tools, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps. To compare the ability of DWI and ADC maps in newborns with HIE to predict the neurodevelopmental outcome at 2 years of age. Thirty-four term newborns with HIE admitted to the Neonatal Intensive Care Unit of Modena University Hospital from 2004 to 2008 were consecutively enrolled in the study. All newborns received EEG, conventional MRI and DWI within the first week of life. DWI was analyzed by means of summation (S) score and regional ADC measurements. Neurodevelopmental outcome was assessed with a standard 1-4 scale and the Griffiths Mental Developmental Scales - Revised (GMDS-R). When the outcome was evaluated with a standard 1-4 scale, the DWI S scores showed very high area under the curve (AUC) (0.89) whereas regional ADC measurements in specific subregions had relatively modest predictive value. The lentiform nucleus was the region with the highest AUC (0.78). When GMDS-R were considered, DWI S scores were good to excellent predictors for some GMDS-R subscales. The predictive value of ADC measurements was both region- and subscale-specific. In particular, ADC measurements in some regions (basal ganglia, white matter or rolandic cortex) were excellent predictors for specific GMDS-R with AUCs up to 0.93. DWI S scores showed the highest prognostic value for the neurological outcome at 2 years of age. Regional ADC measurements in specific subregions proved to be highly prognostic for specific neurodevelopmental outcomes. (orig.)

  18. Prognostic value of brain proton MR spectroscopy and diffusion tensor imaging in newborns with hypoxic-ischemic encephalopathy treated by brain cooling

    Energy Technology Data Exchange (ETDEWEB)

    Ancora, G. [Neonatal Intensive Care Unit, Department of Mother and Infant Infermi Hospital of Rimini, Rimini (Italy); Testa, C.; Tonon, C.; Manners, D.N.; Gramegna, L.L.; Lodi, R. [Department of Biomedical and Neuromotor Sciences University of Bologna, MR Functional Unit, Bologna (Italy); Grandi, S.; Sbravati, F.; Savini, S.; Corvaglia, L.T.; Faldella, G. [University of Bologna, Neonatology Unit, Department of Woman, Child and Adolescent Health, Bologna (Italy); Tani, G. [University of Bologna, Radiology Unit, Department of Woman, Child and Adolescent Health, Bologna (Italy); Malucelli, E. [University of Bologna, Department of Pharmacy and Biotechnologies, Bologna (Italy)

    2013-08-15

    MRI, proton magnetic resonance spectroscopy ({sup 1}H-MRS), and diffusion tensor imaging (DTI) have been shown to be of great prognostic value in term newborns with moderate-severe hypoxic-ischemic encephalopathy (HIE). Currently, no data are available on {sup 1}H-MRS and DTI performed in the subacute phase after hypothermic treatment. The aim of the present study was to assess their prognostic value in newborns affected by moderate-severe HIE and treated with selective brain cooling (BC). Twenty infants treated with BC underwent conventional MRI and {sup 1}H-MRS at a mean (SD) age of 8.3 (2.8) days; 15 also underwent DTI. Peak area ratios of metabolites and DTI variables, namely mean diffusivity (MD), axial and radial diffusivity, and fractional anisotropy (FA), were calculated. Clinical outcome was monitored until 2 years of age. Adverse outcome was observed in 6/20 newborns. Both {sup 1}H-MRS and DTI variables showed higher prognostic accuracy than conventional MRI. N-acetylaspartate/creatine at a basal ganglia localisation showed 100 % PPV and 93 % NPV for outcome. MD showed significantly decreased values in many regions of white and gray matter, axial diffusivity showed the best predictive value (PPV and NPV) in the genu of corpus callosum (100 and 91 %, respectively), and radial diffusivity was significantly decreased in fronto white matter (FWM) and fronto parietal (FP) WM. The decrement of FA showed the best AUC (0.94) in the FPWM. Selective BC in HIE neonates does not affect the early and accurate prognostic value of {sup 1}H-MRS and DTI, which outperform conventional MRI. (orig.)

  19. Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

    Science.gov (United States)

    Wintermark, P; Hansen, A; Warfield, S K; Dukhovny, D; Soul, J S

    2014-01-15

    The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow (CBF) values, measured from 1-2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r=0.88; p value=0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Prognostic value of diffusion-weighted imaging summation scores or apparent diffusion coefficient maps in newborns with hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Cavalleri, Francesca; Lugli, Licia; Pugliese, Marisa; D'Amico, Roberto; Todeschini, Alessandra; Della Casa, Elisa; Gallo, Claudio; Frassoldati, Rossella; Ferrari, Fabrizio

    2014-09-01

    The diagnostic and prognostic assessment of newborn infants with hypoxic-ischemic encephalopathy (HIE) comprises, among other tools, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps. To compare the ability of DWI and ADC maps in newborns with HIE to predict the neurodevelopmental outcome at 2 years of age. Thirty-four term newborns with HIE admitted to the Neonatal Intensive Care Unit of Modena University Hospital from 2004 to 2008 were consecutively enrolled in the study. All newborns received EEG, conventional MRI and DWI within the first week of life. DWI was analyzed by means of summation (S) score and regional ADC measurements. Neurodevelopmental outcome was assessed with a standard 1-4 scale and the Griffiths Mental Developmental Scales - Revised (GMDS-R). When the outcome was evaluated with a standard 1-4 scale, the DWI S scores showed very high area under the curve (AUC) (0.89) whereas regional ADC measurements in specific subregions had relatively modest predictive value. The lentiform nucleus was the region with the highest AUC (0.78). When GMDS-R were considered, DWI S scores were good to excellent predictors for some GMDS-R subscales. The predictive value of ADC measurements was both region- and subscale-specific. In particular, ADC measurements in some regions (basal ganglia, white matter or rolandic cortex) were excellent predictors for specific GMDS-R with AUCs up to 0.93. DWI S scores showed the highest prognostic value for the neurological outcome at 2 years of age. Regional ADC measurements in specific subregions proved to be highly prognostic for specific neurodevelopmental outcomes.

  1. Prognostic value of brain proton MR spectroscopy and diffusion tensor imaging in newborns with hypoxic-ischemic encephalopathy treated by brain cooling

    International Nuclear Information System (INIS)

    Ancora, G.; Testa, C.; Tonon, C.; Manners, D.N.; Gramegna, L.L.; Lodi, R.; Grandi, S.; Sbravati, F.; Savini, S.; Corvaglia, L.T.; Faldella, G.; Tani, G.; Malucelli, E.

    2013-01-01

    MRI, proton magnetic resonance spectroscopy ( 1 H-MRS), and diffusion tensor imaging (DTI) have been shown to be of great prognostic value in term newborns with moderate-severe hypoxic-ischemic encephalopathy (HIE). Currently, no data are available on 1 H-MRS and DTI performed in the subacute phase after hypothermic treatment. The aim of the present study was to assess their prognostic value in newborns affected by moderate-severe HIE and treated with selective brain cooling (BC). Twenty infants treated with BC underwent conventional MRI and 1 H-MRS at a mean (SD) age of 8.3 (2.8) days; 15 also underwent DTI. Peak area ratios of metabolites and DTI variables, namely mean diffusivity (MD), axial and radial diffusivity, and fractional anisotropy (FA), were calculated. Clinical outcome was monitored until 2 years of age. Adverse outcome was observed in 6/20 newborns. Both 1 H-MRS and DTI variables showed higher prognostic accuracy than conventional MRI. N-acetylaspartate/creatine at a basal ganglia localisation showed 100 % PPV and 93 % NPV for outcome. MD showed significantly decreased values in many regions of white and gray matter, axial diffusivity showed the best predictive value (PPV and NPV) in the genu of corpus callosum (100 and 91 %, respectively), and radial diffusivity was significantly decreased in fronto white matter (FWM) and fronto parietal (FP) WM. The decrement of FA showed the best AUC (0.94) in the FPWM. Selective BC in HIE neonates does not affect the early and accurate prognostic value of 1 H-MRS and DTI, which outperform conventional MRI. (orig.)

  2. Positrons as imaging agents and probes in nanotechnology

    International Nuclear Information System (INIS)

    Smith, Suzanne V

    2009-01-01

    Positron emission tomography (PET) tracks a positron emitting radiopharmaceutical injected into the body and generates a 3-dimensional image of its location. Introduced in the early 70s, it has now developed into a powerful medical diagnostic tool for routine clinical use as well as in drug development. Unrivalled as a highly sensitive, specific and non-invasive imaging tool, PET unfortunately lacks the resolution of Computer Tomography (CT) and Magnetic Resonance Imaging (MRI). As the resolution of PET depends significantly on the energy of the positron incorporated in the radiopharmaceutical and its interaction with its surrounding tissue, there is growing interest in expanding our understanding of how positrons interact at the atomic and molecular level. A better understanding of these interactions will contribute to improving the resolution of PET and assist in the design of better imaging agents. Positrons are also used in Positron Annihilation Lifetime Spectroscopy (PALS) to determine electron density and or presence and incidence of micro- and mesopores (0.1 to 10 nm) in materials. The control of porosity in engineered materials is crucial for applications such as controlled release or air and water resistant films. Equally important to the design of nano and microtechnologies, is our understanding of the microenvironments within these pores and on surfaces. Hence as radiopharmaceuticals are designed to track disease, nuclear probes (radioactive molecules) are synthesized to investigate the chemical properties within these pores. This article will give a brief overview of the present role of positrons in imaging as well as explore its potential to contribute in the engineering of new materials to the marketplace.

  3. Formulation of MIBI Kit as a heart imaging agent

    International Nuclear Information System (INIS)

    Widyastuti; A, Hanafiah; Yunilda; A, Laksmi; Setyowati, Sri; Y Veronika

    1999-01-01

    9 9 m Tc labelled 2-methoxy-isobutyl-isonitrile(MIBI) has been known as an imaging agent for myocardial perfusion. This radiopharmaceutical preparation gives the same satisfactory result as Thallium- 2 10TI, and presumably could replace 2 01TI because of same advantages. MIBI kit was formulated from MIBI ligand produced by RPC-BATAN which has been characterized and tested for quality. The formula used in this research referred to the formula of imported product(Cardiolite, MIBI kit produced by Dupont), and the quality control testing was performed by comparing some parameters to the imported product. The parameters used for QC testing were radiochemical purity, biodistribution in nice and heart imaging in human volunteer using gamma camera. The result of the experiment showed that the radiochemical purity was 95 % in average, biodistribution in heart to liver gave the ratio of 0.67, 1.5, and 2.53 respectively at 10, 30 and 60 minutes after injection. The result of clinical testing in some volunteers gave contrast images as good as given by Cardiolite. The optimum condition of freeze drying has been found, and the kit can be used for more than 6 months

  4. Characterization of nanoparticle-based contrast agents for molecular magnetic resonance imaging

    International Nuclear Information System (INIS)

    Shan, Liang; Chopra, Arvind; Leung, Kam; Eckelman, William C.; Menkens, Anne E.

    2012-01-01

    The development of molecular imaging agents is currently undergoing a dramatic expansion. As of October 2011, ∼4,800 newly developed agents have been synthesized and characterized in vitro and in animal models of human disease. Despite this rapid progress, the transfer of these agents to clinical practice is rather slow. To address this issue, the National Institutes of Health launched the Molecular Imaging and Contrast Agents Database (MICAD) in 2005 to provide freely accessible online information regarding molecular imaging probes and contrast agents for the imaging community. While compiling information regarding imaging agents published in peer-reviewed journals, the MICAD editors have observed that some important information regarding the characterization of a contrast agent is not consistently reported. This makes it difficult for investigators to evaluate and meta-analyze data generated from different studies of imaging agents, especially for the agents based on nanoparticles. This article is intended to serve as a guideline for new investigators for the characterization of preclinical studies performed with nanoparticle-based MRI contrast agents. The common characterization parameters are summarized into seven categories: contrast agent designation, physicochemical properties, magnetic properties, in vitro studies, animal studies, MRI studies, and toxicity. Although no single set of parameters is suitable to define the properties of the various types of contrast agents, it is essential to ensure that these agents meet certain quality control parameters at the preclinical stage, so that they can be used without delay for clinical studies.

  5. Uptake of myocardial imaging agents by rejected hearts

    International Nuclear Information System (INIS)

    Bergsland, J.; Carr, E.A.; Carroll, M.; Wright, J.W.; Feldman, M.J.; Massucci, J.; Bhayana, J.N.; Gona, J.M.

    1985-01-01

    Technetium 99 m pyrophosphate, Gallium 67 and Thallium 201 uptakes were measured in heterotopically transplanted rat hearts. Five days after transplantation, Technetium 99 m pyrophosphate, and Gallium 67 uptakes were significantly higher in allogeneic grafts than in syngeneic grafts. At an early stage of rejection (three days after transplantation), only Technetium 99 m pyrophosphate uptake in the left ventricle of allogeneic grafts showed a significant difference (p less than 0.04). At five days, Thallium 201 uptake was significantly lower in allo- than syngeneic grafts. There was a positive correlation between radionuclide uptake and histologic degree of rejection for Technetium 99 m pyrophosphate and Gallium 67 while Thallium 201 uptake correlated negatively. Analysis of variance revealed that hearts with no or minimal rejection had statistically different uptakes than hearts with mild to moderate rejection. These results suggest that uptake of imaging agents might be useful in the diagnosis of rejection of the transplanted heart

  6. Tracers and contrast agents in cardiovascular imaging: present and future

    International Nuclear Information System (INIS)

    Marmion, M.; Deutsch, E.

    1996-01-01

    This brief article addresses the current status and future potential of nuclear medicine, X-ray computed tomography (CT), ultrasound (US), and magnetic resonance (MR) imaging in the diagnosis of cardiovascular diseases. The currently perceived advantages and disadvantages, as well as the possible future roles, of each of the modalities with regard to the evaluation of coronary artery disease are delineated. The certain advent of Mr and US myocardial contrast agents, combined with the inexorable pressures of health care reform, will alter the future usage patterns of all four modalities. Future debates about which modality should be used in which clinical situation will be based not on 'anatomy vs function', nor on the issues of cost effectiveness and patient outcomes

  7. Hypoxic radiosensitization: adored and ignored

    DEFF Research Database (Denmark)

    Overgaard, Jens

    2007-01-01

    resistance can be eliminated or modified by normobaric or hyperbaric oxygen or by the use of nitroimidazoles as hypoxic radiation sensitizers. More recently, attention has been given to hypoxic cytotoxins, a group of drugs that selectively or preferably destroys cells in a hypoxic environment. An updated......Since observations from the beginning of the last century, it has become well established that solid tumors may contain oxygen-deficient hypoxic areas and that cells in such areas may cause tumors to become radioresistant. Identifying hypoxic cells in human tumors has improved by the help of new...

  8. Kit for preparing a technetium-99m myocardial imaging agent

    International Nuclear Information System (INIS)

    Woulfe, S.R.; Deutsch, E.A.; Dyszlewski, M.; Neumann, W.L.

    1992-01-01

    This patent describes a kit for preparing a technetium 99m myocardial imaging agent. It comprises a first vial containing a lyophilized pyrogen free, sterile mixture of an effective reducing agent and a first ligand having the following general formula: wherein the R 1 groups may be the same or different and are selected from the group consisting of hydrogen, hydroxy, C 1 - C 5 alkyl, C 1 - C 5 alkyl substituted by hydroxyl, ether, ester, amide, ketone, aldehyde and nitrile; the R 2 groups may be the same or different and are selected from the group consisting of hydrogen, hydroxy, C 1 - C 5 alkyl, C 1 - C 5 alkyl substituted by hydroxyl, ether, ester, amide, ketone, aldehyde, and nitrile; the X and Y groups may be the same or different and are selected from the group consisting of oxygen and sulfur; and n is equal to 1 or 2; and a second vial containing a lyophilized pyrogen free, sterile protected salt of a phosphine ligand

  9. Contrast agents for tumor diagnosis in magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goto, Rensuke; Doi, Hisayoshi; Okada, Shoji [University of Shizuoka (Japan). School of Pharmaceutical Science; Yano, Masayuki; Katano, Susumu; Nakajima, Nobuaki

    1992-01-01

    In order to develop contrast agents for tumor diagnosis in magnetic resonance imaging (MRI), we investigated the effects of several gadolinium complexes on T{sub 1} relaxation time of proton in some tissues of Ehrlich solid tumor-bearing mice. L-Aspartic acid, L-glutamic acid, DL-homocysteine, L-glutamyl-glutamic acid, glutathione, sperimidine and ethylenediaminetetrakis (methylenephosphate) (EDTMP) were used as ligands for Gd{sup 3+}. Since each Gd-complex could not be purified except Gd-EDTMP, the mixture of GdCl{sub 3} and a ligand was administered intravenously. Among the compounds tested, the mixture of aspartic acid, glutathione or spermidine with GdCl{sub 3} showed almost the same or above reduction of T{sub 1} relaxation times in the tumor tissue compared with Gd-diethylenetriamine pentaacetic acid (Gd-DTPA) which is used clinically. Furthermore, the contrast-enhancing effect of the three mixtures in the tumor was observed by in vivo T{sub 1}-weighted magnetic resonance imaging. The in vivo tissue distribution using radioactive {sup 153}Gd{sup 3+} showed that these mixtures mentioned above were also taken up more highly in the tumor than {sup 153}GdCl{sub 3} itself and {sup 153}Gd-DTPA, suggesting the formation of Gd-complexes. However, the overall tissue distribution of the mixtures was similar to that of {sup 153}GdCl{sub 3} because the Gd-complexes were not purified. Gd-EDTMP exhibited the almost same effects with Gd-DTPA as a contrast agent. (author).

  10. CT diagnosis of hypoxic ischemic encephalopathy

    International Nuclear Information System (INIS)

    Zhao Xiang; Ma Jiwei; Wu Lide

    2004-01-01

    Objective: To explore CT characteristics of hypoxic ischemic encephalopathy (HIE), and to improve the accuracy of CT diagnosis. Methods: 50 cases of neonatal asphyxia in perinatal period diagnosed as hypoxic ischemic encephalopathy by CT was analyzed. Results: The main manifestation of hypoxic ischemic encephalopathy is cerebral edema and intracranial hemorrhage. Focal or diffuse hypo-dense lesion and hyper-dense area in various location and morphology were seen on CT images. (1) Localized diffuse hypo-dense area in 1 or 2 cerebral lobe were found in 17 cases, and the lesions were localized in frontal lobe (n=6), in frontotemporal lobe (n=5), and in temporo-occipital lobe (n=6). (2) Hypo-density region involving more than three cerebral lobes were found in 18 cases, and abnormalities were found in frontotemporal and parietal lobe (n=8), accompanying with subarachnoid hemorrhage (n=2); in frontal, temporal and occipital lobe (n=6), in which cerebral hemorrhage was complicated (n=1); and in other cerebral lobe (n=4). (3) Diffuse low-density region in all cerebral lobe were found in 15 cases, in which subarachnoid hemorrhage was complicated in 4 cases, and ventricular hemorrhage was found in 2 case. Conclusion: CT imaging plays an important role in diagnosis of hypoxic ischemic encephalopathy and has shown its clinical value

  11. Comparison of radiation dosimetry for several potential myocardial imaging agents

    International Nuclear Information System (INIS)

    Watson, E.E.; Stabin, M.G; Goodman, M.M.; Knapp, F.F. Jr.; Srivastava, P.C.

    1986-01-01

    Although myocardial imaging is currently dominated by Tl-201, several alternative agents with improved physiologic or radionuclidic properties have been proposed. Based on human and animal studies in the literature, the metabolism of several of these compounds was studied for the purpose of generating radiation dose estimates. Dose estimates are listed for several I-123-labeled free fatty acids, an I-123-labeled phosphonium compound, Rb-82, Cu-64, F-18 FDG (all compounds which are taken up by the normal myocardium), and for Tc-99m pyrophosphate (PYP) (which localizes in myocardial infarcts). Dose estimates could not be generated for C-11 palmitate, but his compound was included in a comparison of myocardial retention times. For the I-123-labeled compounds, I-124 was included as a contaminant in generating the dose estimates. Radiation doses were lowest for Rb-82 (gonads 0.3-0.4 Gy/MBq, kidneys 8.6 Gy/MBq). Doses for the I-123-labeled fatty acids were similar to one another, with IPPA being the lowest (gonads 15 Gy/MBq, heart wall 18 Gy/MBq). Doses for Tc-99m PYP were also low (gonads 4-7 Gy/MBq, heart wall 4 Gy/MBq, skeleton 15 Gy/MBq). The desirability of these compounds is discussed briefly, considering half-life, imaging mode and energy, and dosimetry, including a comparison of the effective whole body dose equivalents. 37 references, 11 tables

  12. Nicotinic {alpha}4{beta}2 receptor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Pichika, Rama [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Easwaramoorthy, Balasubramaniam [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Collins, Daphne [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Christian, Bradley T. [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Shi, Bingzhi [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Narayanan, Tanjore K. [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Potkin, Steven G. [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Mukherjee, Jogeshwar [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States)]. E-mail: j.mukherjee@uci.edu

    2006-04-15

    The {alpha}4{beta}2 nicotinic acetylcholine receptor (nAChR) has been implicated in various neurodegenerative diseases. Optimal positron emission tomography (PET) imaging agents are therefore highly desired for this receptor. We report here the development and initial evaluation of 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (nifene). In vitro binding affinity of nifene in rat brain homogenate using {sup 3}H-cytisine exhibited a K {sub i}=0.50 nM for the {alpha}4{beta}2 sites. The radiosynthesis of 2-{sup 18}F-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ({sup 18}F-nifene) was accomplished in 2.5 h with an overall radiochemical yield of 40-50%, decay corrected. The specific activity was estimated to be approx. 37-185 GBq/{mu}mol. In vitro autoradiography in rat brain slices indicated selective binding of {sup 18}F-nifene to anteroventral thalamic (AVT) nucleus, thalamus, subiculum, striata, cortex and other regions consistent with {alpha}4{beta}2 receptor distribution. Rat cerebellum showed some binding, whereas regions in the hippocampus had the lowest binding. The highest ratio of >13 between AVT and cerebellum was measured for {sup 18}F-nifene in rat brain slices. The specific binding was reduced (>95%) by 300 {mu}M nicotine in these brain regions. Positron emission tomography imaging study of {sup 18}F-nifene (130 MBq) in anesthetized rhesus monkey was carried out using an ECAT EXACT HR+ scanner. PET study showed selective maximal uptake in the regions of the anterior medial thalamus, ventro-lateral thalamus, lateral geniculate, cingulate gyrus, temporal cortex including the subiculum. The cerebellum in the monkeys showed lower binding than the other regions. Thalamus-to-cerebellum ratio peaked at 30-35 min postinjection to a value of 2.2 and subsequently reduced. The faster binding profile of {sup 18}F-nifene indicates promise as a PET imaging agent and thus needs further evaluation.

  13. Tc-99m labeled Sparfloxacin: A specific infection imaging agent

    International Nuclear Information System (INIS)

    Singh, A.K.; Verma, J.; Bhatnagar, A.; Ali, A.

    2003-01-01

    lesions as well as lesions with infection because of hypervascularity. However, rapid wash out of tracer was noted from sterile inflammatory lesions, while progressive concentration of radiotracer was seen in the lesions with infection. Delayed scans done at two hours post-injection revealed a four fold increase radio tracer concentration at the sites of infection as compared to the sites of sterile inflammation. Based on the results of this preliminary study it was concluded that Tc- 99m Sparfloxacin specifically concentrates in infection in animal models and could potentially be a specific bacterial infection-imaging agent. (author)

  14. 18F-Labelled metomidate analogues as adrenocortical imaging agents

    International Nuclear Information System (INIS)

    Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Langstroem, Bengt

    2009-01-01

    Introduction: Two- and one-step syntheses of 18 F-labelled analogues of metomidate, such as 2-[ 18 F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[ 18 F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[ 18 F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Methods: Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[ 18 F]fluoroethyl 4-methylbenzenesulfonate or 3-[ 18 F]fluoropropyl 4-methylbenzenesulfonate. These were used as 18 F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. Results: The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46±3% and 79±30%, respectively. Conclusion: Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

  15. Hypoxic sensitizers (A review)

    International Nuclear Information System (INIS)

    Ohno, Tadao; Shikita, Mikio

    1976-01-01

    Since the early works of Bridges (1960) and Adams (1963), electron-affinic compounds have long been the subject of a number of studies in the search for a drug which sensitizes radio-resistant hypoxic tumor cells for improvement of radiotherapy of cancer. However, clinical application of this kind of drugs has been hampered by the fact that most of the compounds which exhibited radiosensitizing action in vitro exerted no such action against hypoxic tumor cells in vivo, because of rapid metabolical decomposition or because of great toxicity in vivo. Low solubility of these compounds in aqueous solution was another problem which made it difficult to use the compounds in proper concentrations. The authors have found that furylfuramide (AF-2), possesses a typical radiosensitizing potency. The radiosensitizing action of AF-2 was demonstrated in hypoxic yeasts as well as in mouse leukemic cells (L-5178 Y). Injection of 4.7 μg of AF-2 into a mouse mammary carcinoma 5 min before a single dose (3500 rad) of x-irradiation reduced regrowth of the tumors to a greater extent than irradiation alone, giving an enhancing ratio of 1.6. The effect of AF-2 was insignificant when radiation was given in divided doses (800 rad for 5 times) with the drug injected each time prior to irradiation. (auth.)

  16. Radioresistance and hypoxic cells

    International Nuclear Information System (INIS)

    Ando, Koichi

    1989-01-01

    Current progress to explore further understanding of tumor hypoxia was reviewed. At subcellular level, hypoxia induces specific proteins, inhibits DNA synthesis as well as initiation of DNA replicon. Radioresistant characteristics of hypoxic cells is questioned in condition where irradiated cells were kept hypoxia during colony formation. Chronically hypoxic cells recovered from the inner layer of V79 multicellular spheroids are more sensitive to radiation than those from the oxic, outer layer. A novel sandwich culture method, which enables to reoxygenate chronic hypoxia, implies that chronically hypoxic cells are less sensitive to radiation after reoxygenation than oxic cells. For in vivo tumor, two types of tumor hypoxia are reported: diffusion-limited, chronic hypoxia and perfusion-limited, acute hypoxia. Evidence supporting the existence of perfusion-limited hypoxia is provided by an elegant method using vital staining and cell sorter. Data of our own laboratory also implies 2 types of tumor hypoxia; fractional hypoxia and incomplete hypoxia. Fractional hypoxia corresponds to a radioresistant tail on a biphasic tumor cell survival curves while tumors with incomplete hypoxia demonstrate only single component with radioresistant characteristics, instead. (author)

  17. Hypoxic-cell sensitizers

    International Nuclear Information System (INIS)

    Dische, S.

    1983-01-01

    There is now 6 years of clinical experience with misonidazole as a hypoxic-cell sensitizer. Neurotoxicity limits the total dose which may be given, and so relatively low concentrations of radiosensitizing drugs are likely to be achieved in hypoxic cells in man as compared with those in animal tumors. It is likely that benefit will only be shown in those situations where radioresistant hypoxic cells strongly dominate as a cause of radiation failure. Many clinical trials are underway, and thus far some show no benefit while in others there is a definite advantage to the patients given the drug. These trials must be continued to their conclusion, but misonidazole must be regarded as the first of a series of radiosensitizers to reach the clinic for trial. There is a promise of more effective drugs becoming available within the next few years. Those showing a lower lipophilicity than misonidazole have been found to have a shorter half-life and a lower uptake in neural tissue in animal studies. One such drug, desmethylmisonidazole, is presently undergoing clinical trial

  18. Semi-quantitative Assessment of Brain Maturation by Conventional Magnetic Resonance Imaging in Neonates with Clinically Mild Hypoxic-ischemic Encephalopathy

    Science.gov (United States)

    Gao, Jie; Sun, Qin-Li; Zhang, Yu-Miao; Li, Yan-Yan; Li, Huan; Hou, Xin; Yu, Bo-Lang; Zhou, Xi-Hui; Yang, Jian

    2015-01-01

    Background: Mild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI). Methods: Totally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups. Results: The mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased. Conclusions: The TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes

  19. Adapting radiotherapy to hypoxic tumours

    Science.gov (United States)

    Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag

    2006-10-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields

  20. Adapting radiotherapy to hypoxic tumours

    International Nuclear Information System (INIS)

    Malinen, Eirik; Soevik, Aste; Hristov, Dimitre; Bruland, Oeyvind S; Olsen, Dag Rune

    2006-01-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO 2 -related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO 2 -related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO 2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO 2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure

  1. A review of 99mTc labeled myocardial imaging agents for tumor-positive imaging

    International Nuclear Information System (INIS)

    Xing Shian; Zhang Yongxue; An Rui

    2002-01-01

    The tumor-positive imaging with high sensitivity and specificity was useful in primary tumor and recurrences and metastases. The 99m Tc labeled myocardial imaging agents are easily available and stable and the radiochemical purity is high. 99m Tc is the preferred choice in routine works because its physical properties. The preparation, quality control, mechanism of accumulation and the clinical use of 99m Tc-sestamibi, 99m Tc-tetrofosmin, 99m Tc-furifosmin, and 99m Tc-N-NOET were reviewed

  2. Gold nanoparticle cellular uptake, toxicity and radiosensitisation in hypoxic conditions

    International Nuclear Information System (INIS)

    Jain, Suneil; Coulter, Jonathan A.; Butterworth, Karl T.; Hounsell, Alan R.; McMahon, Stephen J.; Hyland, Wendy B.; Muir, Mark F.; Dickson, Glenn R.; Prise, Kevin M.; Currell, Fred J.; Hirst, David G.; O’Sullivan, Joe M.

    2014-01-01

    Background and purpose: Gold nanoparticles (GNPs) are novel agents that have been shown to cause radiosensitisation in vitro and in vivo. Tumour hypoxia is associated with radiation resistance and reduced survival in cancer patients. The interaction of GNPs with cells in hypoxia is explored. Materials and methods: GNP uptake, localization, toxicity and radiosensitisation were assessed in vitro under oxic and hypoxic conditions. Results: GNP cellular uptake was significantly lower under hypoxic than oxic conditions. A significant reduction in cell proliferation in hypoxic MDA-MB-231 breast cancer cells exposed to GNPs was observed. In these cells significant radiosensitisation occurred in normoxia and moderate hypoxia. However, in near anoxia no significant sensitisation occurred. Conclusions: GNP uptake occurred in hypoxic conditions, causing radiosensitisation in moderate, but not extreme hypoxia in a breast cancer cell line. These findings may be important for the development of GNPs for cancer therapy

  3. Radioiodinated carnitine and acylcarnitine analogs as potential myocardial imaging agents

    International Nuclear Information System (INIS)

    McConnell, D.S.

    1991-01-01

    R-carnitine is extremely important in mammalian energy metabolism. Gamma-butyrobetaine, the immediate biosynthetic precursor to R-carnitine, is synthesized in many organs. However, only liver can hydroxylate gamma-butyrobetaine to carnitine. Thus the transport of carnitine from its site of synthesis to the site of utilization is of utmost importance. Carnitine is found in highest concentration in cardiac and skeletal muscle, where it is required for the transport of fatty acids into the mitochondria. Before fatty acids are utilized as fuel for the myocyte by beta-oxidation, they are bound to carnitine as an acylcarnitine ester at the 3-hydroxyl, and transported across the micochondrial membranes. R,S-Carnitine has been shown to be taken up by myocytes. The author has begun a study on the use of carnitine derivatives as potential carriers for the site-specific delivery of radioiodine to bidning sites in the myocardium. Such agents labeled with a gamma-emitting nuclide such as iodine-123 would be useful for the noninvasive imaging of these tissues. The aim was to synthesize a variety of radiolabeled analogs of carnitine and acylcarnitine to address questions of transport, binding and availability for myocardial metabolism. These analogs consist of N-alkylated derivatives of carnitine, acylcarnitine esters as well as carnitine amides and ethers. One C-alkylated derivative showed interesting biodistribution, elevated myocardial uptake and competition with carnitine for binding in the myocardium

  4. Development of Iron Doped Silicon Nanoparticles as Bimodal Imaging Agents

    Science.gov (United States)

    Singh, Mani P.; Atkins, Tonya M.; Muthuswamy, Elayaraja; Kamali, Saeed; Tu, Chuqiao; Louie, Angelique Y.; Kauzlarich, Susan M.

    2012-01-01

    We demonstrate the synthesis of water-soluble allylamine terminated Fe doped Si (SixFe) nanoparticles as bimodal agents for optical and magnetic imaging. The preparation involves the synthesis of a single source iron containing precursor, Na4Si4 with x% Fe (x = 1, 5, 10), and its subsequent reaction with NH4Br to produce hydrogen terminated SixFe nanoparticles. The hydrogen-capped nanoparticles are further terminated with allylamine via thermal hydrosilylation. Transmission electron microscopy (TEM) indicates that the average particle diameter is ~3.0±1.0 nm. The Si5Fe nanoparticles show strong photoluminescence quantum yield in water (~ 10 %) with significant T2 contrast (r2/r1value of 4.31). Electron paramagnetic resonance (EPR) and Mössbauer spectroscopies indicate that iron in the nanoparticles is in the +3 oxidation state. Analysis of cytotoxicity using the resazurin assay on HepG2 liver cells indicates that the particles have minimal toxicity. PMID:22616623

  5. DTPA: Bis benzimidazole as multi model imaging agent

    International Nuclear Information System (INIS)

    Srivastava, Vikas; Tiwari, A.K.; Sharma, H.; Sharma, R.; Mishra, A.K.

    2010-01-01

    Full text: The DTPA bis benzimidazole analogue has been tested for radiopharmaceutical efficacy. The radiolabelling was found more then 98% after 8 hrs and blood kinetics was fast. The compound was also tested for optical imaging agent. The Eu 3+ ion has an absorption band in the visible spectrum (578-582 nm) whose wavelength is very sensitive to even small changes in the coordination environment. Although the intensity of this 7F0 → 5D0 transition is low, the bands are relatively narrow, which allows distinguishing different coordination states of the metal. For Eu 3+ complexes which have two differently hydrated forms in aqueous solution, one observes two absorption bands belonging to the two species. High-resolution UV-visible spectra were recorded in aqueous solutions which show a temperature invariant absorption with two distinct, temperature-dependent absorption bands. The intensity ratio of these two bands changes with temperature: the band at shorter wavelengths is decreasing very slightly, while that at longer wavelengths is increasing with the temperature. The ratio of the integrals of the two bands is related to the equilibrium constant, and its temperature dependence yields the reaction enthalpy and entropy

  6. Meeting Report: High-Throughput Technologies for In Vivo Imaging Agents

    Directory of Open Access Journals (Sweden)

    Robert J. Gillies

    2005-04-01

    Full Text Available Combinatorial chemistry and high-throughput screening have become standard tools for discovering new drug candidates with suitable pharmacological properties. Now, those same technologies are starting to be applied to the problem of discovering novel in vivo imaging agents. Important differences in the biological and pharmacological properties needed for imaging agents, compared to those for a therapeutic agent, require new screening methods that emphasize those characteristics, such as optimized residence time and tissue specificity, that make for a good imaging agent candidate.

  7. Ultrasound contrast-agent improves imaging of lower limb occlusive disease

    DEFF Research Database (Denmark)

    Eiberg, J P; Hansen, M A; Jensen, F

    2003-01-01

    to evaluate if ultrasound contrast-agent infusion could improve duplex-ultrasound imaging of peripheral arterial disease (PAD) and increase the agreement with digital subtraction arteriography (DSA).......to evaluate if ultrasound contrast-agent infusion could improve duplex-ultrasound imaging of peripheral arterial disease (PAD) and increase the agreement with digital subtraction arteriography (DSA)....

  8. In vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent

    Science.gov (United States)

    2016-11-01

    AD______________ AWARD NUMBER: W81XWH-14-1-0242 TITLE: In Vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent PRINCIPAL...TITLE AND SUBTITLE In vivo Photoacoustic Imaging of Prostate Cancer Using T argeted Contrast Agent 5a. CONTRACT NUMBER W81XWH-14-1-0242 5b. GRANT...diagnose prostate cancer based on the near-infrared optical absorption of either endogenous tissue constituents or exogenous contrast agents . Although

  9. Radioiodinated fenetylline (captagon): A new potential brain imaging agent

    International Nuclear Information System (INIS)

    Biersack, H.J.; Klunenberg, H.; Breuel, H.P.; Reske, S.N.; Reichmann, K.; Winkler, C.

    1984-01-01

    Since about 2 years /sup 123/I-labeled iodamphetamines (IMP) and diamines (HIPDM) have been used for scintigraphic brain investigations. As another possibly useful brain imaging agent we studied radioiodine labeled Fenetylline which is metabolized into amphetamine. Thirty wistar rats were injected 5 μCi /sup 125/I-IMP and 2 μCi /sup 131/I-Fenetylline each simultaneously. The animals were sacrificed 5,10,15,30,60, and 120 min. p.i. The radioactivity content of tissue specimens (brain, cerebellum, liver, kidney, lung, myocardium, muscle) was measured in a well-counter (% dose/g tissue). In 2 dogs sequential cerebral scintigraphy was performed following the injection of 0.5 mCi /sup 131/I-Fenetylline. Three patients underwent brain SPECT after injection of 6.5 mCi /sup 123/I-Fenetylline. The results can be summarized as follows: after 5/10 min. p.i. Fenetylline-uptake in the brain of rats was 1.0/1.3% compared to 1.3/1.9% (IMP). A fast decrease of cerebral Fenetylline concentration was established after 30 (0.2%) and 60 (0.5%) min. The canine and human sequential scintigraphy revealed a rapid cerebral uptake (maximum after 2-10 min.) suggesting that Fenetylline is concentrated in the brain as a function of cerebral blood flow. From the first clinical findings it appears to be likely that the combined use of /sup 123/I labelled IMP and Fenetylline for SPECT may lead to a more differentiated evaluation of cerebral blood flow and metabolism

  10. Prospective of 68Ga Radionuclide Contribution to the Development of Imaging Agents for Infection and Inflammation

    Science.gov (United States)

    2018-01-01

    During the last decade, the utilization of 68Ga for the development of imaging agents has increased considerably with the leading position in the oncology. The imaging of infection and inflammation is lagging despite strong unmet medical needs. This review presents the potential routes for the development of 68Ga-based agents for the imaging and quantification of infection and inflammation in various diseases and connection of the diagnosis to the treatment for the individualized patient management. PMID:29531507

  11. Understanding Hypoxic Drive and the Release of Hypoxic Vasoconstriction.

    Science.gov (United States)

    Inkrott, Jon C

    2016-01-01

    Understanding the hypoxic drive and release of hypoxic vasoconstriction in the chronic obstructive pulmonary disease population can be somewhat confusing and misunderstood. Furthermore, the hypoxic drive theory is one in which there really is no scientific evidence to support and yet continues to prosper in every aspect of care in regard to the chronic lung patient, from prehospital all the way to intensive care unit and home care therapy. This subject review will hopefully enhance some understanding of what exactly goes on with these patients and the importance of providing oxygen when it is desperately needed. Copyright © 2016 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.

  12. Ultrasound contrast agent imaging: Real-time imaging of the superharmonics

    Energy Technology Data Exchange (ETDEWEB)

    Peruzzini, D.; Viti, J. [MSD lab, Department of Information Engineering, Univ of Florence, Via S.Marta, 3, 50139 Firenze (Italy); Erasmus MC, ’s-Gravendijkwal 230, Faculty Building, Ee 2302, 3015 CE Rotterdam (Netherlands); Tortoli, P. [MSD lab, Department of Information Engineering, Univ of Florence, Via S.Marta, 3, 50139 Firenze (Italy); Verweij, M. D. [Acoustical Wavefield Imaging, ImPhys, Delft Univ Technology, van der Waalsweg 8, 2628 CH Delft (Netherlands); Jong, N. de; Vos, H. J., E-mail: h.vos@erasmusmc.nl [Erasmus MC, ’s-Gravendijkwal 230, Faculty Building, Ee 2302, 3015 CE Rotterdam (Netherlands); Acoustical Wavefield Imaging, ImPhys, Delft Univ Technology, van der Waalsweg 8, 2628 CH Delft (Netherlands)

    2015-10-28

    Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher harmonics, i.e. “superharmonic” imaging, shows better contrast. However, the superharmonic scattering has a lower signal level compared to e.g. second harmonic signals. This study investigates the contrast-to-tissue ratio (CTR) and signal to noise ratio (SNR) of superharmonic UCA scattering in a tissue/vessel mimicking phantom using a real-time clinical scanner. Numerical simulations were performed to estimate the level of harmonics generated by the microbubbles. Data were acquired with a custom built dual-frequency cardiac phased array probe. Fundamental real-time images were produced while beam formed radiofrequency (RF) data was stored for further offline processing. The phantom consisted of a cavity filled with UCA surrounded by tissue mimicking material. The acoustic pressure in the cavity of the phantom was 110 kPa (MI = 0.11) ensuring non-destructivity of UCA. After processing of the acquired data from the phantom, the UCA-filled cavity could be clearly observed in the images, while tissue signals were suppressed at or below the noise floor. The measured CTR values were 36 dB, >38 dB, and >32 dB, for the second, third, and fourth harmonic respectively, which were in agreement with those reported earlier for preliminary contrast superharmonic imaging. The single frame SNR values (in which ‘signal’ denotes the signal level from the UCA area) were 23 dB, 18 dB, and 11 dB, respectively. This indicates that noise, and not the tissue signal, is the limiting factor for the UCA detection when using the superharmonics in nondestructive mode.

  13. Design and Optimization of Gadolinium Based Contrast Agents for Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Pereira, G.A.; Geraldes, C.F.G.C.; University of Coimbra

    2007-01-01

    The role of Gd 3+ chelates as contrast agents in Magnetic Resonance Imaging is discussed. The theory describing the different contributions to paramagnetic relaxation relevant to the understanding of the molecular parameters determining the relativity of those Gd 3+ chelates, is presented. The experimental techniques used to obtain those parameters are also described. Then, the various approaches taken to optimize those parameters, leading to maximum relativity (efficiency) of the contrast agents, are also illustrated with relevant examples taken from the literature. The various types of Gd 3+ -based agents, besides non-specific and hepatobiliary agents, are also discussed, namely blood pool, targeting, responsive and paramagnetic chemical shift saturation transfer (PARACEST) agents. Finally, a perspective is presented of some of the challenges lying ahead in the optimization of MRI contrast agents to be useful in Molecular Imaging. (author)

  14. Microbubble embedded with upconversion nanoparticles as a bimodal contrast agent for fluorescence and ultrasound imaging

    International Nuclear Information System (INIS)

    Jin, Birui; Lin, Min; You, Minli; Xu, Feng; Lu, Tianjian; Zong, Yujin; Wan, Mingxi; Duan, Zhenfeng

    2015-01-01

    Bimodal imaging offers additional imaging signal thus finds wide spread application in clinical diagnostic imaging. Fluorescence/ultrasound bimodal imaging contrast agent using fluorescent dyes or quantum dots for fluorescence signal has emerged as a promising method, which however requires visible light or UV irradiation resulting in photobleaching, photoblinking, auto-fluorescence and limited tissue penetration depth. To surmount these problems, we developed a novel bimodal contrast agent using layer-by-layer assembly of upconversion nanoparticles onto the surface of microbubbles. The resulting microbubbles with average size of 2 μm provide enhanced ultrasound echo for ultrasound imaging and upconversion emission upon near infrared irradiation for fluorescence imaging. The developed bimodal contrast agent holds great potential to be applied in ultrasound target technique for targeted diseases diagnostics and therapy. (paper)

  15. Spectral Imaging Technology-Based Evaluation of Radiation Treatment Planning to Remove Contrast Agent Artifacts.

    Science.gov (United States)

    Yi-Qun, Xu; Wei, Liu; Xin-Ye, Ni

    2016-10-01

    This study employs dual-source computed tomography single-spectrum imaging to evaluate the effects of contrast agent artifact removal and the computational accuracy of radiotherapy treatment planning improvement. The phantom, including the contrast agent, was used in all experiments. The amounts of iodine in the contrast agent were 30, 15, 7.5, and 0.75 g/100 mL. Two images with different energy values were scanned and captured using dual-source computed tomography (80 and 140 kV). To obtain a fused image, 2 groups of images were processed using single-energy spectrum imaging technology. The Pinnacle planning system was used to measure the computed tomography values of the contrast agent and the surrounding phantom tissue. The difference between radiotherapy treatment planning based on 80 kV, 140 kV, and energy spectrum image was analyzed. For the image with high iodine concentration, the quality of the energy spectrum-fused image was the highest, followed by that of the 140-kV image. That of the 80-kV image was the worst. The difference in the radiotherapy treatment results among the 3 models was significant. When the concentration of iodine was 30 g/100 mL and the distance from the contrast agent at the dose measurement point was 1 cm, the deviation values (P) were 5.95% and 2.20% when image treatment planning was based on 80 and 140 kV, respectively. When the concentration of iodine was 15 g/100 mL, deviation values (P) were -2.64% and -1.69%. Dual-source computed tomography single-energy spectral imaging technology can remove contrast agent artifacts to improve the calculated dose accuracy in radiotherapy treatment planning. © The Author(s) 2015.

  16. Microscopic validation of whole mouse micro-metastatic tumor imaging agents using cryo-imaging and sliding organ image registration

    Science.gov (United States)

    Liu, Yiqiao; Zhou, Bo; Qutaish, Mohammed; Wilson, David L.

    2016-03-01

    We created a metastasis imaging, analysis platform consisting of software and multi-spectral cryo-imaging system suitable for evaluating emerging imaging agents targeting micro-metastatic tumor. We analyzed CREKA-Gd in MRI, followed by cryo-imaging which repeatedly sectioned and tiled microscope images of the tissue block face, providing anatomical bright field and molecular fluorescence, enabling 3D microscopic imaging of the entire mouse with single metastatic cell sensitivity. To register MRI volumes to the cryo bright field reference, we used our standard mutual information, non-rigid registration which proceeded: preprocess --> affine --> B-spline non-rigid 3D registration. In this report, we created two modified approaches: mask where we registered locally over a smaller rectangular solid, and sliding organ. Briefly, in sliding organ, we segmented the organ, registered the organ and body volumes separately and combined results. Though sliding organ required manual annotation, it provided the best result as a standard to measure other registration methods. Regularization parameters for standard and mask methods were optimized in a grid search. Evaluations consisted of DICE, and visual scoring of a checkerboard display. Standard had accuracy of 2 voxels in all regions except near the kidney, where there were 5 voxels sliding. After mask and sliding organ correction, kidneys sliding were within 2 voxels, and Dice overlap increased 4%-10% in mask compared to standard. Mask generated comparable results with sliding organ and allowed a semi-automatic process.

  17. [Utilization of polymeric micelle magnetic resonance imaging (MRI) contrast agent for theranostic system].

    Science.gov (United States)

    Shiraishi, Kouichi

    2013-01-01

    We applied a polymeric micelle carrier system for the targeting of a magnetic resonance imaging (MRI) contrast agent. Prepared polymeric micelle MRI contrast agent exhibited a long circulation characteristic in blood, and considerable amount of the contrast agent was found to accumulate in colon 26 solid tumor by the EPR effect. The signal intensities of tumor area showed 2-folds increase in T1-weighted images at 24 h after i.v. injection. To observe enhancement of the EPR effect by Cderiv pretreatment on tumor targeting, we used the contrast agent for the evaluation by means of MRI. Cderiv pretreatment significantly enhanced tumor accumulation of the contrast agent. Interestingly, very high signal intensity in tumor region was found at 24 h after the contrast agent injection in Cderiv pretreated mice. The contrast agent visualized a microenvironmental change in tumor. These results indicate that the contrast agent exhibits potential use for tumor diagnostic agent. To combine with a polymeric micelle carrier system for therapeutic agent, the usage of the combination makes a new concept of "theranostic" for a better cancer treatment.

  18. Cranial nerve contrast using nerve-specific fluorophores improved by paired-agent imaging with indocyanine green as a control agent

    Science.gov (United States)

    Torres, Veronica C.; Vuong, Victoria D.; Wilson, Todd; Wewel, Joshua; Byrne, Richard W.; Tichauer, Kenneth M.

    2017-09-01

    Nerve preservation during surgery is critical because damage can result in significant morbidity. This remains a challenge especially for skull base surgeries where cranial nerves (CNs) are involved because visualization and access are particularly poor in that location. We present a paired-agent imaging method to enhance identification of CNs using nerve-specific fluorophores. Two myelin-targeting imaging agents were evaluated, Oxazine 4 and Rhodamine 800, and coadministered with a control agent, indocyanine green, either intravenously or topically in rats. Fluorescence imaging was performed on excised brains ex vivo, and nerve contrast was evaluated via paired-agent ratiometric data analysis. Although contrast was improved among all experimental groups using paired-agent imaging compared to conventional, solely targeted imaging, Oxazine 4 applied directly exhibited the greatest enhancement, with a minimum 3 times improvement in CNs delineation. This work highlights the importance of accounting for nonspecific signal of targeted agents, and demonstrates that paired-agent imaging is one method capable of doing so. Although staining, rinsing, and imaging protocols need to be optimized, these findings serve as a demonstration for the potential use of paired-agent imaging to improve contrast of CNs, and consequently, surgical outcome.

  19. Development of a Multifaceted Ovarian Cancer Therapeutic and Imaging Agent

    Science.gov (United States)

    2011-04-01

    by 1-ethyl-3- [3-(dimethylamino) propyl ]carbodiimide (EDC) and N-hydroxysulfonosuccinimide (SNHS) at pH 5.5 for 30 min with a molar ratio of...particle-coated migratory substrate that can act as a permanent record of cellular movement. The gold chloride solution was prepared using 0.342 g... Synthesis and clinical Evaluation. Anticancer Agents Med. Chem. McLane, M.A., Joerger, T., Mahmoud, A., 2008. Disintegrins in health and disease. Front

  20. High-Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Werner, Eric J.; Datta, Ankona; Jocher, Christoph J.; Raymond, Kenneth N.

    2008-01-15

    The desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues such as solubility and in vivo toxicity must also be addressed, making the attainment of safe, high-relaxivity agents a challenging goal. Here we present recent advances in the field, with an emphasis on the hydroxypyridinone family of Gd{sup III} chelates.

  1. Metal complex-based templates and nanostructures for magnetic resonance/optical multimodal imaging agents

    NARCIS (Netherlands)

    Galindo Millan, Jealemy

    2012-01-01

    In this thesis, new approaches directed towards simple and functional imaging agents (IAs) for magnetic resonance (MR) and fluorescence multimodal imaging are proposed. In Chapter 3, hybrid silver nanostructures (hAgNSs), grown using a polyamino carboxylic acid scaffold, namely

  2. EPR and DNP Properties of Certain Novel Single Electron Contrast Agents Intended for Oximetric Imaging

    DEFF Research Database (Denmark)

    Ardenkjær-Larsen, J. H.; Laursen, I; Leunbach, I.

    1998-01-01

    Parameters of relevance to oximetry with Overhauser magnetic resonance imaging (OMRI) have been measured for three single electron contrast agents of the triphenylmethyl type. The single electron contrast agents are stable and water soluble. Magnetic resonance properties of the agents have been...... examined with electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), and dynamic nuclear polarization (DNP) at 9.5 mT in water, isotonic saline, plasma, and blood at 23 and 37°C. The relaxivities of the agents are about 0.2–0.4 mM−1s−1and the DNP enhancements extrapolate close...... to the dipolar limit. The agents have a single, narrow EPR line, which is analyzed as a Voigt function. The linewidth is measured as a function of the agent concentration and the oxygen concentration. The concentration broadenings are about 1–3 μT/mM and the Lorentzian linewidths at infinite dilution are less...

  3. Biochemical Stability Analysis of Nano Scaled Contrast Agents Used in Biomolecular Imaging Detection of Tumor Cells

    Science.gov (United States)

    Kim, Jennifer; Kyung, Richard

    Imaging contrast agents are materials used to improve the visibility of internal body structures in the imaging process. Many agents that are used for contrast enhancement are now studied empirically and computationally by researchers. Among various imaging techniques, magnetic resonance imaging (MRI) has become a major diagnostic tool in many clinical specialties due to its non-invasive characteristic and its safeness in regards to ionizing radiation exposure. Recently, researchers have prepared aqueous fullerene nanoparticles using electrochemical methods. In this paper, computational simulations of thermodynamic stabilities of nano scaled contrast agents that can be used in biomolecular imaging detection of tumor cells are presented using nanomaterials such as fluorescent functionalized fullerenes. In addition, the stability and safety of different types of contrast agents composed of metal oxide a, b, and c are tested in the imaging process. Through analysis of the computational simulations, the stabilities of the contrast agents, determined by optimized energies of the conformations, are presented. The resulting numerical data are compared. In addition, Density Functional Theory (DFT) is used in order to model the electron properties of the compound.

  4. Use of radiolabeled antibodies as diagnostic imaging agents

    International Nuclear Information System (INIS)

    Wang, T.S.T.; Seldin, D.; Fawwaz, R.A.; Srivastava, S.; Olvwole, S.

    1989-01-01

    Recent advances in hybridoma technology have led to the development of monoclonal antibodies to a variety of antigens. The high degree of specificity of such reagents coupled with refinements in instrumentation and production of new radionuclides has rekindled interest in the application of radioimmunoscintigraphy in the diagnosis of various diseases. Although much of the work with monoclonal antibodies has been devoted to the diagnosis and treatment of tumors, increasing use is being made of these agents for the study of nontumor related disorders. This chapter focuses on the application of radioimmunoscintigraphy in the diagnosis of malignancies with a discussion on the other uses, notably those related to the vascular system

  5. Molecular imaging agents for SPECT (and SPECT/CT)

    International Nuclear Information System (INIS)

    Gnanasegaran, Gopinath; Ballinger, James R.

    2014-01-01

    The development of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) cameras has increased the diagnostic value of many existing single photon radiopharmaceuticals. Precise anatomical localization of lesions greatly increases diagnostic confidence in bone imaging of the extremities, infection imaging, sentinel lymph node localization, and imaging in other areas. Accurate anatomical localization is particularly important prior to surgery, especially involving the parathyroid glands and sentinel lymph node procedures. SPECT/CT plays a role in characterization of lesions, particularly in bone scintigraphy and radioiodine imaging of metastatic thyroid cancer. In the development of novel tracers, SPECT/CT is particularly important in monitoring response to therapies that do not result in an early change in lesion size. Preclinical SPECT/CT devices, which actually have spatial resolution superior to PET/CT devices, have become essential in characterization of the biodistribution and tissue kinetics of novel tracers, allowing coregistration of serial studies within the same animals, which serves both to reduce biological variability and reduce the number of animals required. In conclusion, SPECT/CT increases the utility of existing radiopharmaceuticals and plays a pivotal role in the evaluation of novel tracers. (orig.)

  6. Molecular imaging agents for SPECT (and SPECT/CT)

    Energy Technology Data Exchange (ETDEWEB)

    Gnanasegaran, Gopinath [Guy' s and St Thomas' NHS Foundation Trust, Department of Nuclear Medicine, London (United Kingdom); Ballinger, James R. [Guy' s and St Thomas' NHS Foundation Trust, Department of Nuclear Medicine, London (United Kingdom); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

    2014-05-15

    The development of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) cameras has increased the diagnostic value of many existing single photon radiopharmaceuticals. Precise anatomical localization of lesions greatly increases diagnostic confidence in bone imaging of the extremities, infection imaging, sentinel lymph node localization, and imaging in other areas. Accurate anatomical localization is particularly important prior to surgery, especially involving the parathyroid glands and sentinel lymph node procedures. SPECT/CT plays a role in characterization of lesions, particularly in bone scintigraphy and radioiodine imaging of metastatic thyroid cancer. In the development of novel tracers, SPECT/CT is particularly important in monitoring response to therapies that do not result in an early change in lesion size. Preclinical SPECT/CT devices, which actually have spatial resolution superior to PET/CT devices, have become essential in characterization of the biodistribution and tissue kinetics of novel tracers, allowing coregistration of serial studies within the same animals, which serves both to reduce biological variability and reduce the number of animals required. In conclusion, SPECT/CT increases the utility of existing radiopharmaceuticals and plays a pivotal role in the evaluation of novel tracers. (orig.)

  7. Fluorescence lifetime imaging microscopy using near-infrared contrast agents.

    Science.gov (United States)

    Nothdurft, R; Sarder, P; Bloch, S; Culver, J; Achilefu, S

    2012-08-01

    Although single-photon fluorescence lifetime imaging microscopy (FLIM) is widely used to image molecular processes using a wide range of excitation wavelengths, the captured emission of this technique is confined to the visible spectrum. Here, we explore the feasibility of utilizing near-infrared (NIR) fluorescent molecular probes with emission >700 nm for FLIM of live cells. The confocal microscope is equipped with a 785 nm laser diode, a red-enhanced photomultiplier tube, and a time-correlated single photon counting card. We demonstrate that our system reports the lifetime distributions of NIR fluorescent dyes, cypate and DTTCI, in cells. In cells labelled separately or jointly with these dyes, NIR FLIM successfully distinguishes their lifetimes, providing a method to sort different cell populations. In addition, lifetime distributions of cells co-incubated with these dyes allow estimate of the dyes' relative concentrations in complex cellular microenvironments. With the heightened interest in fluorescence lifetime-based small animal imaging using NIR fluorophores, this technique further serves as a bridge between in vitro spectroscopic characterization of new fluorophore lifetimes and in vivo tissue imaging. © 2012 The Author Journal of Microscopy © 2012 Royal Microscopical Society.

  8. Combined blood pool and extracellular contrast agents for pediatric and young adult cardiovascular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Joyce T. [Ann and Robert Lurie Children' s Hospital of Chicago, Division of Pediatric Cardiology, 225 E. Chicago Ave., Box 21, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Robinson, Joshua D. [Ann and Robert Lurie Children' s Hospital of Chicago, Division of Pediatric Cardiology, 225 E. Chicago Ave., Box 21, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Deng, Jie [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Rigsby, Cynthia K. [Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States)

    2016-12-15

    A comprehensive cardiac magnetic resonance (cardiac MR) study including both late gadolinium enhancement (LGE) and MR angiography may be indicated for patients with a history of acquired or congenital heart disease. To study the novel use of an extracellular agent for assessment of LGE combined with a blood pool contrast agent for detailed MR angiography evaluation to yield a comprehensive cardiac MR study in these patients. We reviewed clinical cardiac MR studies utilizing extracellular and blood pool contrast agents and noted demographics, clinical data and adverse events. We rated LGE image quality and MR angiography image quality for each vascular segment and calculated inter-rater variability. We also quantified contrast-to-noise ratio (CNR). Thirty-three patients (mean age 13.9 ± 3 years) received an extracellular contrast agent (10 gadobenate dimeglumine, 23 gadopentetate dimeglumine) and blood pool contrast agent (33 gadofosveset trisodium). No adverse events were reported. MRI indications included Kawasaki disease (8), cardiomyopathy and coronary anatomy (15), repaired congenital heart disease (8), and other (2). Mean LGE quality was 2.6 ± 0.6 with 97% diagnostic imaging. LGE quality did not vary by type of contrast agent given (P = 0.07). Mean MR angiography quality score was 4.7 ± 0.6, with high inter-rater agreement (k = 0.6-0.8, P < 0.002). MR angiography quality did not vary by type of contrast agent used (P = 0.6). Cardiac MR studies utilizing both extracellular and blood pool contrast agents are feasible and safe and provide excellent-quality LGE and MR angiography images. The use of two contrast agents allows for a comprehensive assessment of both myocardial viability and vascular anatomy during the same exam. (orig.)

  9. Combined blood pool and extracellular contrast agents for pediatric and young adult cardiovascular magnetic resonance imaging

    International Nuclear Information System (INIS)

    Johnson, Joyce T.; Robinson, Joshua D.; Deng, Jie; Rigsby, Cynthia K.

    2016-01-01

    A comprehensive cardiac magnetic resonance (cardiac MR) study including both late gadolinium enhancement (LGE) and MR angiography may be indicated for patients with a history of acquired or congenital heart disease. To study the novel use of an extracellular agent for assessment of LGE combined with a blood pool contrast agent for detailed MR angiography evaluation to yield a comprehensive cardiac MR study in these patients. We reviewed clinical cardiac MR studies utilizing extracellular and blood pool contrast agents and noted demographics, clinical data and adverse events. We rated LGE image quality and MR angiography image quality for each vascular segment and calculated inter-rater variability. We also quantified contrast-to-noise ratio (CNR). Thirty-three patients (mean age 13.9 ± 3 years) received an extracellular contrast agent (10 gadobenate dimeglumine, 23 gadopentetate dimeglumine) and blood pool contrast agent (33 gadofosveset trisodium). No adverse events were reported. MRI indications included Kawasaki disease (8), cardiomyopathy and coronary anatomy (15), repaired congenital heart disease (8), and other (2). Mean LGE quality was 2.6 ± 0.6 with 97% diagnostic imaging. LGE quality did not vary by type of contrast agent given (P = 0.07). Mean MR angiography quality score was 4.7 ± 0.6, with high inter-rater agreement (k = 0.6-0.8, P < 0.002). MR angiography quality did not vary by type of contrast agent used (P = 0.6). Cardiac MR studies utilizing both extracellular and blood pool contrast agents are feasible and safe and provide excellent-quality LGE and MR angiography images. The use of two contrast agents allows for a comprehensive assessment of both myocardial viability and vascular anatomy during the same exam. (orig.)

  10. Amphetamines and pH-shift agents for brain imaging

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Winkler, C.

    1986-01-01

    This book gives a review of the results of experimental and clinical research on both I-amphetamine derivatives and pH-shift agents. Virtually all relevant working groups from the USA and Europe have contributed to this volume. The pharmacology of amphetamine and the corresponding receptor theories are described in detail, whereas other chapters deal with the labeling as well as the metabolic process of this drug. In addition to this, new amphetamine derivatives are presented together with other essential products which play a significant role in scintigraphy of the brain function. Finally, there are two chapters on instrumentation problems followed by eight contributions on the clinical results of amphetamine scintigraphy in cerebral vascular diseases, epilepsy, migraine and brain tumors.

  11. Towards a framework for agent-based image analysis of remote-sensing data.

    Science.gov (United States)

    Hofmann, Peter; Lettmayer, Paul; Blaschke, Thomas; Belgiu, Mariana; Wegenkittl, Stefan; Graf, Roland; Lampoltshammer, Thomas Josef; Andrejchenko, Vera

    2015-04-03

    Object-based image analysis (OBIA) as a paradigm for analysing remotely sensed image data has in many cases led to spatially and thematically improved classification results in comparison to pixel-based approaches. Nevertheless, robust and transferable object-based solutions for automated image analysis capable of analysing sets of images or even large image archives without any human interaction are still rare. A major reason for this lack of robustness and transferability is the high complexity of image contents: Especially in very high resolution (VHR) remote-sensing data with varying imaging conditions or sensor characteristics, the variability of the objects' properties in these varying images is hardly predictable. The work described in this article builds on so-called rule sets. While earlier work has demonstrated that OBIA rule sets bear a high potential of transferability, they need to be adapted manually, or classification results need to be adjusted manually in a post-processing step. In order to automate these adaptation and adjustment procedures, we investigate the coupling, extension and integration of OBIA with the agent-based paradigm, which is exhaustively investigated in software engineering. The aims of such integration are (a) autonomously adapting rule sets and (b) image objects that can adopt and adjust themselves according to different imaging conditions and sensor characteristics. This article focuses on self-adapting image objects and therefore introduces a framework for agent-based image analysis (ABIA).

  12. Fluorine-18 nuclide and its PET imaging agent

    International Nuclear Information System (INIS)

    Wang Mingfang

    2003-01-01

    Fluorine-18 has predominant physical features with long half-life and the enough time for preparation of radiopharmaceuticals and PET imaging. Also, the chemical nature of fluorine-18 is similar to that of hydrogen, and the fluorine-18 labelled organic molecules can not change the non-labelled molecular character. Therefore, fluorine-18 is widely applied in the labelled glucose, amino acids, fatty acids, nucleotide, receptor-ligand and neurotransmitter molecular etc., with the propose of detecting the blood flow, metabolism, synthesis of the protein and the neurotransmitter function in brain by PET imaging. It is very important in the basic science and clinical research to understand and master the preparation of the fluorine-18 and its labelled compounds

  13. Elemental imaging of MRI contrast agents: benchmarking of LA-ICP-MS to MRI

    Energy Technology Data Exchange (ETDEWEB)

    Pugh, J.A.T. [University of Sheffield, Centre for Analytical Sciences, Sheffield (United Kingdom); University of Sheffield, Department of Chemical and Biological Engineering, Sheffield (United Kingdom); Cox, A.G.; McLeod, C.W. [University of Sheffield, Centre for Analytical Sciences, Sheffield (United Kingdom); Bunch, J. [University of Birmingham, School of Chemistry, Birmingham (United Kingdom); Writer, M.J.; Hart, S.L. [UCL Institute of Child Health, Wolfson Centre for Gene Therapy of Childhood Disease, London (United Kingdom); Bienemann, A.; White, E. [University of Bristol, School of Clinical Sciences, Southmead Hospital, Bristol (United Kingdom); Bell, J. [Hammersmith Hospital, Metabolic and Molecular Imaging Group, MRC Clinical Sciences Centre, Imperial College London, London (United Kingdom)

    2012-06-15

    Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been used to map the spatial distribution of magnetic resonance imaging (MRI) contrast agents (Gd-based) in histological sections in order to explore synergies with in vivo MRI. Images from respective techniques are presented for two separate studies namely (1) convection enhanced delivery of a Gd nanocomplex (developmental therapeutic) into rat brain and (2) convection enhanced delivery, with co-infusion of Magnevist (commercial Gd contrast agent) and Carboplatin (chemotherapy drug), into pig brain. The LA technique was shown to be a powerful compliment to MRI not only in offering improved sensitivity, spatial resolution and signal quantitation but also in giving added value regarding the fate of administered agents (Gd and Pt agents). Furthermore simultaneous measurement of Fe enabled assignment of an anomalous contrast enhancement region in rat brain to haemorrhage at the infusion site. (orig.)

  14. Patterns of neonatal hypoxic-ischaemic brain injury

    International Nuclear Information System (INIS)

    Vries, Linda S. de; Groenendaal, Floris

    2010-01-01

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  15. Patterns of neonatal hypoxic-ischaemic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Linda S. de [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands); Wilhelmina Children' s Hospital, University Medical Centre, Department of Neonatology, KE 04.123.1, P.O. Box 85090, Utrecht (Netherlands); Groenendaal, Floris [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands)

    2010-06-15

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  16. Diagnosis of Popliteal Venous Entrapment Syndrome by Magnetic Resonance Imaging Using Blood-Pool Contrast Agents

    International Nuclear Information System (INIS)

    Beitzke, Dietrich; Wolf, Florian; Juelg, Gregor; Lammer, Johannes; Loewe, Christian

    2011-01-01

    Popliteal vascular entrapment syndrome is caused by aberrations or hypertrophy of the gastrocnemius muscles, which compress the neurovascular structures of the popliteal fossa, leading to symptoms of vascular and degeneration as well as aneurysm formation. Imaging of popliteal vascular entrapment may be performed with ultrasound, magnetic resonance imaging (MRI), computed tomography angiography, and conventional angiography. The use of blood-pool contrast agents in MRI when popliteal vascular entrapment is suspected offers the possibility to perform vascular imaging with first-pass magnetic resonance angiographic, high-resolution, steady-state imaging and allows functional tests all within one examination with a single dose of contrast agent. We present imaging findings in a case of symptomatic popliteal vein entrapment diagnosed by the use of blood pool contrast-enhanced MRI.

  17. Progress of study on the dopamine D4 receptor imaging agent

    International Nuclear Information System (INIS)

    Tian Haibin; Zhang Lan; Zhang Chunfu; Li Junling; Yin Duanzhi

    2001-01-01

    Dopamine receptors were originally classified into five receptors subtypes, the dopamine D 4 receptor was included. Schizophrenic pathophysiology may be associated with expression and function of the dopamine D 4 receptor; it is of great importance to study the imaging agent of dopamine D 4 receptor. The study on radioactivity distribution and metabolize of radioligand remains hampered by the lack radioligand for the D 4 receptor which can be labeled using suitable nuclei. This paper reviews the progress of study on the dopamine D 4 receptor imaging agent, with particular emphasis vary nuclei, for example 11 C, 18 F, 123 I, labeled D 4 receptor ligands, antagonists and analogs as PET or SPECT imaging agents. Authors estimated affinity and selectivity of radioligands for the dopamine D 4 receptor in laboratory animal tests

  18. Gd-DTPA as a paramagnetic contrast agent in MR imaging of focal liver lesions

    International Nuclear Information System (INIS)

    Hamm, B.; Roemer, T.; Wolf, K.J.; Felix, R.; Weinmann, H.J.

    1986-01-01

    Gd-DTPA enhances signal intensity in healthy liver and in intrahepatic tumors. However, after contrast agent administration, tumor enhances significantly more than liver parenchyma (2α≤ 0.05). Doubling the dose of Gd-DTPA from 0.1 to 0.2 mmol/kg of body weight increases the enhancement of intrahepatic tumors (2α≤ 0.05) and optimizes the contrast between tumor and liver in T1-weighted spin-echo sequences. However, the contrast between tumor and liver on inversion-recovery and T2-weighted images obtained before contrast agent administration is much greater than the difference on T1-weighted images obtained after contrast agent administration (2α≤ 0.05). In fast images the contrast between liver and tumor can be markedly improved by administering Gd-DTPA

  19. Microbubbles as contrast agent for in-line x-ray phase-contrast imaging

    International Nuclear Information System (INIS)

    Xi Yan; Zhao Jun; Tang Rongbiao; Wang Yujie

    2011-01-01

    In the present study, we investigated the potential of gas-filled microbubbles as contrast agents for in-line x-ray phase-contrast imaging (PCI) in biomedical applications. When imaging parameters are optimized, the microbubbles function as microlenses that focus the incoming x-rays to form bright spots, which can significantly enhance the image contrast. Since microbubbles have been shown to be safe contrast agents in clinical ultrasonography, this contrast-enhancement procedure for PCI may have promising utility in biomedical applications, especially when the dose of radiation is a serious concern. In this study, we performed both numerical simulations and ex vivo experiments to investigate the formation of the contrast and the effectiveness of microbubbles as contrast agents in PCI.

  20. Diethylenetriaminepentaacetic acid-gadolinium (DTPA-Gd)-conjugated polysuccinimide derivatives as magnetic resonance imaging contrast agents.

    Science.gov (United States)

    Lee, Ha Young; Jee, Hye Won; Seo, Sung Mi; Kwak, Byung Kook; Khang, Gilson; Cho, Sun Hang

    2006-01-01

    Biocompatible polysuccinimide (PSI) derivatives conjugated with diethylenetriaminepentaacetic acid gadolinium (DTPA-Gd) were prepared as magnetic resonance imaging (MRI) contrast agents. In this study, we synthesized PSI derivatives incorporating methoxy-poly(ethylene glycol) (mPEG) as hydrophilic ligand, hexadecylamine as hydrophobic ligand, and DTPA-Gd as contrast agent. PSI was synthesized by the polycondensation polymerization of aspartic acid. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Critical micellization concentrations were determined using fluorescent probes (pyrene). Micelle size and shape were measured by electro-photometer light scattering (ELS) and atomic force microscopy (AFM). The formed micelle size ranged from 100 to 300 nm. The T1-weighted MR images of the phantom prepared with PSI-mPEG-C16-(DTPA-Gd) were obtained in a 3.0 T clinical MR imager, and the conjugates showed a great potential as MRI contrast agents.

  1. Evaluation of nitrobenzimidazoles as hypoxic cell radiosensitizers

    International Nuclear Information System (INIS)

    Wright, J.; Frank, L.R.; Bush, D.; Harrison, G.H.

    1983-01-01

    Radiobiological and pharmacokinetic assays were performed to determine the potential of 2-nitrobenzimidazole (NBI) as a hypoxic cell radiosensitizing agent. As judged by comparing survival curve slopes of Serratia marcescens irradiated under aerated and hypoxic conditions, the NBI enhancement ratio (ER) at 2 mM concentration was 2.4 +- 0.2, compared with an oxygen enhancement ratio of 3.3 +- 0.3. 2,5-Dinitrobenzimidazole (DNBI) was investigated in vitro; its ER was 3.0 +- 0.3 at 4 mM concentration. Very poor tissue penetration of DNBI precluded further testing in vivo. Acute toxic signs appeared in C3H/HeJ mice following ip injection of NBI at 100 mg/kg. These would be partly attributable to the stress caused by the high pH of the injection vehicle. The LD 50 was estimated to be 125 to 150 mg/kg. Mammary adenocarcinoma tumors grown in the flanks of these mice exhibited maximum NBI levels at 5 min postinjection (ip). Peak tumor radiosensitization occurred in the interval between 5 and 10 min postinjection. The ER for tumor regrowth delay was 2.1 +- 0.3 following 50 mg/kg injected into mice 5 min before irradiation. Functional evaluation up to 40 days after treatment revealed no evidence of neurological deficit

  2. Evaluation of nitrobenzimidazoles as hypoxic cell radiosensitizers

    International Nuclear Information System (INIS)

    Wright, J.; Frank, L.R.; Bush, D.; Harrison, G.H.

    1983-01-01

    Radiobiological and pharmacokinetic assays were performed to determine the potential of 2-nitrobenzimidazole (NBI) as a hypoxic cell radiosensitizing agent. As judged by comparing survival curve slopes of Serratia marcescens irradiated under aerated and hypoxic conditions, the NBI enhancement ratio (ER) at 2 mM concentration was 2.4 +/- 0.2, compared with an oxygen enhancement ratio of 3.3 +/- 0.3. 2,5-Dinitrobenzimidazole (DNBI) was investigated in vitro; its ER was 3.0 +/- 0.3 at 4 mM concentration. Very poor tissue penetration of DNBI precluded further testing in vivo. Acute toxic signs appeared in C3H/HeJ mice following ip injection of NBI at 100 mg/kg. These would be partly attributable to the stress caused by the high pH of the injection vehicle. The LD50 was estimated to be 125-150 mg/kg. Mammary adenocarcinoma tumors grown in the flanks of these mice exhibited maximum NBI levels at 5 min postinjection (ip). Peak tumor radiosensitization occurred in the interval between 5 and 10 min postinjection. The ER for tumor regrowth delay was 2.1 +/- 0.3 following 50 mg/kg injected into mice 5 min before irradiation. Functional evaluation up to 40 days after treatment revealed no evidence of neurological deficit

  3. Bimodal MR-PET agent for quantitative pH imaging

    Science.gov (United States)

    Frullano, Luca; Catana, Ciprian; Benner, Thomas; Sherry, A. Dean; Caravan, Peter

    2010-01-01

    Activatable or “smart” magnetic resonance contrast agents have relaxivities that depend on environmental factors such as pH or enzymatic activity, but the MR signal depends on relaxivity and agent concentration – two unknowns. A bimodal approach, incorporating a positron emitter, solves this problem. Simultaneous positron emission tomography (PET) and MR imaging with the biomodal, pH-responsive MR-PET agent GdDOTA-4AMP-F allows direct determination of both concentration (PET) and T1 (MRI), and hence pH. PMID:20191650

  4. Submicron polycaprolactone particles as a carrier for imaging contrast agent for in vitro applications.

    Science.gov (United States)

    Iqbal, Muhammad; Robin, Sophie; Humbert, Philippe; Viennet, Céline; Agusti, Geraldine; Fessi, Hatem; Elaissari, Abdelhamid

    2015-12-01

    Fluorescent materials have recently attracted considerable attention due to their unique properties and high performance as imaging agent in biomedical fields. Different imaging agents have been encapsulated in order to restrict its delivery to a specific area. In this study, a fluorescent contrast agent was encapsulated for in vitro application by polycaprolactone (PCL) polymer. The encapsulation was performed using modified double emulsion solvent evaporation technique with sonication. Fluorescent nanoparticles (20 nm) were incorporated in the inner aqueous phase of double emulsion. A number of samples were fabricated using different concentrations of fluorescent contrast agent. The contrast agent-containing submicron particle was characterized by a zetasizer for average particle size, SEM and TEM for morphology observations and fluorescence spectrophotometer for encapsulation efficiency. Moreover, contrast agent distribution in the PCL matrix was determined by confocal microscopy. The incorporation of contrast agent in different concentrations did not affect the physicochemical properties of PCL particles and the average size of encapsulated particles was found to be in the submicron range. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

    Science.gov (United States)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

    2016-05-05

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

  6. The use contrast agent for imaging biological samples

    Czech Academy of Sciences Publication Activity Database

    Dammer, J.; Weyda, František; Sopko, V.; Jakůbek, J.

    2011-01-01

    Roč. 6, C01096 (2011), s. 1-7 ISSN 1748-0221. [International Workshop on Radiation Imaging Detectors /12./. Cambridge, 11.07.2010-15.7.2010] R&D Projects: GA MŠk 2B06005 Grant - others:Research Program(CZ) 6840770029; Research Program(CZ) 6840770040; GA AV ČR(CZ) IAA600550614; GA MŠk(CZ) 2B06007; GA MŠk(CZ) 1PO4LA211; GA MŠk(CZ) LC06041 Program:IA; 2B; LC Institutional research plan: CEZ:AV0Z50070508 Keywords : x-ray radiography and digital radiography (DR) * x-ray detectors * inspections with x-rays Subject RIV: EA - Cell Biology Impact factor: 1.869, year: 2011

  7. Study of new 113mIn-BAT complexes for myocardial imaging agents

    International Nuclear Information System (INIS)

    Zhu Lin; Liu Boli; Kojima, M.

    1991-01-01

    Some new BAT derivatives are designed and synthesized in order to find some ideal myocardial imaging agents. These ligands form pentacoordinated complexes with indium cation. The structures of ligand BAT-TE and complexes In-BAT-TE and In-BAT-ETE are determined by X-ray crystallography at first. Biodistribution shows that the higher lipophilicity of complex induces apparently higher myocardial accumulation. Up to date, complex B is the best 113m In-labeled myocardial imaging agent. It is also suited to 111 In

  8. Iron-EHPG as an hepatobiliary MR contrast agent: initial imaging and biodistribution studies

    International Nuclear Information System (INIS)

    Lauffer, R.B.; Greif, W.L.; Stark, D.D.; Vincent, A.C.; Saini, S.; Wedeen, V.J.; Brady, T.J.

    1988-01-01

    A paramagnetic relaxation agent targeted to functioning hepatocytes of the liver and excreted into the bile would be useful in the enhancement of normal liver and biliary anatomy in MR imaging. We sought to demonstrate the feasibility of this approach using the prototype hepatobiliary MR contrast agent, iron(III) ethylenebis-(2-hydroxyphenylglycine) (Fe(EHPG) - ). The biodistribution, relaxation enhancement, and imaging characteristics of Fe(EHPG) - were compared to those of the non-specific iron chelate iron(III) diethylenetriaminepentaacetic acid (Fe(DTPA) 2- ), which has a comparable effect on water proton relaxation times. (author)

  9. Potentially three distinct roles for hypoxic cell sensitizers in the clinic

    International Nuclear Information System (INIS)

    Chapman, J.D.; Raleigh, J.A.; Pedersen, J.E.; Ngan, J.; Shum, F.Y.

    1979-01-01

    Nitroaromatic drugs have been applied to radiation therapy on the basis of their effectiveness to enhance radiation damages selectively in hypoxic mammalian cells at nontoxic concentration. Such sensitizers could improve the rate of local tumor control by conventional radiotherapy in such cases that the resistance due to hypoxia in a limiting factor. The selective cytotoxicity of the drug to hypoxic cells is the second distinct action. A third potential role for nitroaromatic drugs could involve their use for the diagnosis of the number and location of hypoxic cells within tumors. The gain in therapeutic ratio by a factor from 5 to 10 is necessary before the full clinical impact of hypoxic cell radiosensitizers can be evaluated. The drugs selected for the use as clinical radiosensitizers were originally developed as the antibacterial agents with selective activity against anaerobes. The hypoxic cells in tumors are usually resistant to chemotherapy as well as resistant to radiation, and this specific drug action of sensitizers combined with that of an agent effective against oxygenated and cycling cells could possibly produce improved tumor cures. Electron-affinitive chemicals become selectively bound to the macromolecules of hypoxic mammalian cells by radiation-induced chemical reaction. This technique was used to identify by autoradiographic procedures the location of the radioactive nitrofurazone bound to hypoxic cells within multicellular spheroids. (Yamashita, S.)

  10. Development of Tc-99m labeled myocardial imaging agent

    International Nuclear Information System (INIS)

    Jeong, J. M.; Jang, Y. S.; Kim, Y. J.; Lee, Y. S.; Kim, H. W.; Ray, G.; Lee, M. S.

    2006-02-01

    Lipophilic cations have been widely used for myocardial SPECT. We synthesized novel +1 charged lipophilic Tc-99m-labeled N,N'-disubstituted N2S2 derivatives and investigated their biodistribution. The N,N'-dimethyl-, N,N'-diethyl-, N,N'-bis(methoxyethyl)-, and N,N'-bis(ethoxyethyl)N2S2 derivatives were synthesized by alkylating disulfide form of N2S2 with corresponding alkyl halides and subsequently reduced with LAH in THF. To label with Tc-99m, 50% gluconic acid (0.1 ml), SnCl2·2H2O (10 μg), Tc-99m-pertechnetate (370 MBq/2.5 ml) and 0.5 M Na2CO3 (0.3 ml) were added to the compounds. These mixtures were reacted in boiling water bath for 30∼60 min. Radiochemical purities were checked by Whatman No.1 chromatography (normal saline, Rf 0.3∼0.4). Biodistribution of each compound was investigated after injecting 74 kBq (0.1 ml) of each Tc-99m-labeled compound to ICR-mice through the tail vein. Chemical structures of synthesized compounds were confirmed by GC-MSD and 1H-NMR spectroscopy. All of the Tc-99m-labeled compound showed labeling efficiencies of higher than 93%. In biodistribution study, the myocardial uptake of Tc-99m-N,N'-dimethylN2S2, Tc-99m-N,N'-diethylN2S2, Tc-99m-N,N'-bis(methoxyethyl)N2S2 and Tc-99m-N,N'-bis(ethoxyethyl)N2S2 were 5.38 ±0.96, 2.98 ±0.16, 4.27 ±0.47, 7.24 ±1.01% ID/g at 10 min and 5.34 ±1.57, 2.05 ±0.40, 1.02 ±0.16, 1.69 ±0.04% ID/g at 2 hr, respectively. We successfully synthesized Tc-99m-labeled N,N-disubstituted N2S2 derivatives that are novel lipophilic +1 charged compounds. We thought our results prove the feasibility of these compounds to use for myocardial SPECT agent

  11. Comparison of positive and negative enteral contrast agents for MR imaging of the abdomen

    International Nuclear Information System (INIS)

    Kaminsky, S.; Langer, M.

    1994-01-01

    Following oral administration of a buffered gadopentetate-dimeglumine solution (Magnevist enteral R , 1 mmol/l, 6-17 ml/kg) T 1 -, proton-density- and T 2 -weighted spin-echo images of abdominal and retroperitoneal lesions were acquired (0.5 T). Gadopentetate is a signal-enhancing, positive MR contrast agent, intraluminar air served as a model of a signal-free, negative agent. In 21 patients contrast/noise ratios of gadopentetate and air versus lesions and fat were compared quantitatively (t-test). In T 1 - and T 2 -weighted images contrast/noise ratios of gadopentetate versus lesions were significantly higher than those of air. In proton-density images there was no significant difference. In T 1 - and proton-density images contrast/noise ratios of air versus abdominal fat were significantly higher than those of gadopentetate, in T 2 -weighted images gadopentetate had a significantly higher contrast/noise ratio than air. Signal-enhancing positive contrast agents seem advantageous over signal-free negative enteral MR contrast agents. (orig.) [de

  12. Gadolinium-porphyrins: new potential magnetic resonance imaging contrast agents for melanoma detection

    Directory of Open Access Journals (Sweden)

    Daryoush Shahbazi-Gahrouei

    2006-11-01

    Full Text Available BACKGROUND: Two new porphyrin-based magnetic resonance imaging (MRI contrast agents, Gd-hematoporphyrin (Gd-H and Gd-tetra-carboranylmethoxyphenyl-porphyrin (Gd-TCP were synthesized and tested in nude mice with human melanoma (MM-138 xenografts as new melanoma contrast agents. METHODS: Subcutaneous xenografts of human melanoma cells (MM-138 were studied in 30 (five groups of six nude mice. The effect of different contrast agents (Gd-TCP, Gd-H, GdCl3 and Gd-DTPA on proton relaxation times was measured in tumors and other organs. T1 values, signal enhancement and the Gd concentration for different contrast agent solutions were also investigated. RESULTS: The porphyrin agents showed higher relaxivity compared to the clincal agent, Gd-DTPA. A significant 16% and 21% modification in T1 relaxation time of the water in human melanoma tumors grafted in the nude mice was revealed 24 hours after injection of Gd-TCP and Gd-H, respectively. The percentage of injected Gd localized to the tumor measured by inductively coupled plasma atomic emission spectrometry (ICP-AES was approximately 21% for Gd-TCP and 28% for Gd-H which were higher than that of Gd-DTPA (10%. CONCLUSIONS: The high concentration of Gd in the tumor is indicative of a selective retention of the compounds and indicates that Gd-TCP and Gd-H are promising MR imaging contrast agents for melanoma detection. Gd-porphyrins have considerable promise for further diagnostic applications in magnetic resonance imaging. KEY WORDS: MRI, porphyrin-based contrast agent, hematoporphyrin, melanoma.

  13. Analogues of estradiol as potential breast tumor imaging agents

    International Nuclear Information System (INIS)

    Gibson, R.E.; Rzeszotarski, W.J.; Ferriera, N.L.; Jagoda, E.M.; Reba, R.C.; Eckelman, W.C.

    1984-01-01

    The radioiodinated analogue of estradiol, 11β-methoxy-17α-[/sup 125/I]iodovinylestradiol (MIVE/sub 2/), has been shown to be a good candidate for the imaging of estrogen dependent breast tumors. Although there has been no extensive study on the sensitivity of radiotracers of this type, the authors have not observed localization of the radiotracer in metastatic lesions containing less than 20 fmole estrogen receptor/mg protein or in bone metasteses. In order to improve the sensitivity, they have examined several structural analogues of moxestrol (the parent structure for MIVE/sub 2/) for affinity to the ER isolated from immature rat uterus. The 11β-ethyl analogue (EEE/sub 2/) of ethynyl estradiol (EE/sub 2/) exhibits the highest affinity with the 11β-methyl analogue second best. Although the lipophilicity is also very high this compound should not be much more lipophilic than 16-iodoestradiol or MIVE/sub 2/ since the introduction of iodine increases the log P by greater than 1. The distribution of the tritiated derivative of EEE/sub 2/ is under study

  14. Perinatal Hypoxic-Ischemic brain injury; MR findings

    International Nuclear Information System (INIS)

    Park, Dong Woo; Seo, Chang Hye

    1994-01-01

    To characterize the MR findings of hypoxic-ischemic brain injury and to assess the value of the MR imaging. SE T1-, T2-weighted, and IR brain MR images of 44 infants and children with the past history of perinatal hypoxic insults were reviewed. Abnormal brain MR findings of 8 patients with birth history of prematurity and 36 patients with birth history of full-term/posterm including 7 with severe anoxic insult history, were compared in regard to the location and the character of the lesions. MRI demonstrated the followings; (1)abnormal signal intensity lesions of subcortical and/or deep cerebral white matter, cortex, and deep gray matter, (2)atrophy of the cerebral white matter, cortex and corpus callosum, with/without ventriculomegaly, and (3)delay in myelination. Periventricular and deep white matter lesions were demonstrated in the prematurity, the deep white matter lesions and/ or subcortical white matter lesions in the term/post-term, and deep gray matter lesions in the 7 patients with severe anoxic insults history. MR imaging was useful in the diagnosis of the hypoxic-ischemic brain injury, and the white and gray matter lesions were correlated with the time of the injury and the severity of hypoxic insult

  15. Studies on polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents

    International Nuclear Information System (INIS)

    Yan Guoping; Liu Maili; Li Liyun

    2005-01-01

    Purpose: A series of polyaspartamide gadolinium complexes containing pyridoxamine groups were studied as the potential magnetic resonance imaging (MRI) contrast agents for liver enhancement. Methods: These polyaspartamide gadolinium complexes were prepared and evaluated by relaxivity, acute toxicity studies and magnetic resonance imaging of the liver in rats. Results: These polyaspartamide gadolinium complexes have higher relaxation effectiveness than that of the clinically used gadolinium diethylenetriaminepentaacetic acid and possess the low intravenous acute toxicities to Institute for Cancer Research (ICR) mice. Magnetic resonance imaging of the liver in rats indicated that they greatly enhance the contrast of magnetic resonance images and provide prolonged intravascular duration in the liver. Conclusion: These results indicated that the polyaspartamide gadolinium complexes containing pyridoxamine groups could be considered as the appropriate MRI contrast agents for liver enhancement

  16. Imaging efficiency of an X-ray contrast agent-incorporated polymeric microparticle.

    Science.gov (United States)

    Ahn, Sungsook; Jung, Sung Yong; Lee, Jin Pyung; Lee, Sang Joon

    2011-01-01

    Biocompatible polymeric encapsulants have been widely used as a delivery vehicle for a variety of drugs and imaging agents. In this study, X-ray contrast agent (iopamidol) is encapsulated into a polymeric microparticle (polyvinyl alcohol) as a particulate flow tracer in synchrotron X-ray imaging system. The physical properties of the designed microparticles are investigated and correlated with enhancement in the imaging efficiency by experimental observation and theoretical interpretation. The X-ray absorption ability of the designed microparticle is assessed by Beer-Lambert-Bouguer law. Particle size, either in dried state or in solvent, primarily dominates the X-ray absorption ability under the given condition, thus affecting imaging efficiency of the designed X-ray contrast flow tracers. Copyright © 2011 John Wiley & Sons, Ltd.

  17. Contrast agents and cardiac MR imaging of myocardial ischemia: from bench to bedside

    International Nuclear Information System (INIS)

    Croisille, Pierre; Revel, Didier; Saeed, Maythem

    2006-01-01

    This review paper presents, in the first part, the different classes of contrast media that are already used or are in development for cardiac magnetic resonance imaging. A classification of the different types of contrast media is proposed based on the distribution of the compounds in the body, their type of relaxivity and their potential affinity to particular molecules. In the second part, the different uses of the extracellular type of T1-enhancing contrast agent for myocardial imaging is covered from the detection of stable coronary artery disease to the detection and characterization of chronic infarction. A particular emphasis is placed on the clinical use of gadolinium-chelates, which are the universally used type of MRI contrast agent in the clinical routine. Both approaches, first-pass magnetic resonance imaging (FP-MRI) as well as delayed-enhanced magnetic resonance imaging (DE-MRI), are covered in the different situations of acute and chronic myocardial infarction. (orig.)

  18. Assessment of myocardial infarction by magnetic resonance imaging with the aid of contrast agents

    International Nuclear Information System (INIS)

    Roos, A. de; Doornbos, J.

    1991-01-01

    The potential of MR imaging in myocardial ischemia with low-temporal-resolution spin-echo techniques both with and without MR contrast agents has been explored. There are indications that early MR imaging after administration of Gd-DTPA is capable to differentiate reperfused from non-reperfused infarcts. Furthermore, MR infarct sizing using Gd-DTPA is feasible to demonstrate infarct size reduction in patients with successful reperfusion. (H.W.). 50 refs.; 9 figs

  19. Renal perfusion image using harmonic ultrasound with microbble contrast agent: preliminary study

    International Nuclear Information System (INIS)

    Kim, Jung Hoon; Choi, Jae Ho; Han, Dong Chul; Lee, Hi Bahl; Choi, Deuk Lin; Eun, Hyo Won; Lee, Hun Jae

    2003-01-01

    To compare, in terms of their feasibility and normal range, 99m Tc-DTPA renal perfusion imaging and renal perfusion imaging using harmonic ultrasound (US) with a microbubble contrast agent for the evaluation of renal perfusion after renal transplantation. During a six-month period, thirty patients who had received a renal transplant underwent both 99m Tc-DTPA renal perfusion imaging and renal perfusion imaging using harmonic US with a microbubble contrast agent. Sonographic renal perfusion images were obtained before and after a bolus injection of the microbubble contrast agent Levovist TM (SH U 5084; Schering AG, Berlin, Germany) every 3 seconds for 3 minutes. Sonographic renal perfusion images were converted into a renal perfusion curve by a computer program and T peak of the curve thus obtained was compared with that of the 99m Tc-DTPA curve. Average T peak of the 99m Tc-DTPA renal perfusion curve was 16.2 seconds in the normal group and 39.6 seconds in the delayed perfusion group, while average T peak of the sonographic renal perfusion curve was 23.7 seconds and 46.2 seconds, respectively. T peak of the sonographic renal perfusion curve showed a good correlation with that of the 99m Tc-DTPA curve (correlation coefficient=0.8209; p=0.0001). The cut-off value of T peak of the sonographic renal perfusion curve was 35 seconds (sensitivity=90%, specificity=95%). In patients who have received a renal transplant, the findings of renal perfusion imaging using harmonic US with a microbubble contrast agent show close correlation with those of 99m Tc-DTPA renal perfusion imaging. The optimal cut-off value of T peak of the sonographic renal perfusion curve was 35 seconds

  20. Examining multi-component DNA-templated nanostructures as imaging agents

    Science.gov (United States)

    Jaganathan, Hamsa

    2011-12-01

    Magnetic resonance imaging (MRI) is the leading non-invasive tool for disease imaging and diagnosis. Although MRI exhibits high spatial resolution for anatomical features, the contrast resolution is low. Imaging agents serve as an aid to distinguish different types of tissues within images. Gadolinium chelates, which are considered first generation designs, can be toxic to health, while ultra-small, superparamagnetic nanoparticles (NPs) have low tissue-targeting efficiency and rapid bio-distribution, resulting to an inadequate detection of the MRI signal and enhancement of image contrast. In order to improve the utility of MRI agents, the challenge in composition and structure needs to be addressed. One-dimensional (1D), superparamagnetic nanostructures have been reported to enhance magnetic and in vivo properties and therefore has a potential to improve contrast enhancement in MRI images. In this dissertation, the structure of 1D, multi-component NP chains, scaffolded on DNA, were pre-clinically examined as potential MRI agents. First, research was focused on characterizing and understanding the mechanism of proton relaxation for DNA-templated NP chains using nuclear magnetic resonance (NMR) spectrometry. Proton relaxation and transverse relaxivity were higher in multi-component NP chains compared to disperse NPs, indicating the arrangement of NPs on a 1D structure improved proton relaxation sensitivity. Second, in vitro evaluation for potential issues in toxicity and contrast efficiency in tissue environments using a 3 Tesla clinical MRI scanner was performed. Cell uptake of DNA-templated NP chains was enhanced after encapsulating the nanostructure with layers of polyelectrolytes and targeting ligands. Compared to dispersed NPs, DNA-templated NP chains improved MRI contrast in both the epithelial basement membrane and colon cancer tumors scaffolds. The last part of the project was focused on developing a novel MRI agent that detects changes in DNA methylation

  1. Synchrotron-based DEI for bio-imaging and DEI-CT to image phantoms with contrast agents

    International Nuclear Information System (INIS)

    Rao, Donepudi V.; Swapna, Medasani; Cesareo, Roberto; Brunetti, Antonio; Akatsuka, Tako; Yuasa, Tetsuya; Zhong, Zhong; Takeda, Tohoru; Gigante, Giovanni E.

    2012-01-01

    The introduction of water, physiological, or iodine as contrast agents is shown to enhance minute image features in synchrotron-based X-ray diffraction radiographic and tomographic imaging. Anatomical features of rat kidney, such as papillary ducts, ureter, renal artery and renal vein are clearly distinguishable. Olfactory bulb, olfactory tact, and descending bundles of the rat brain are visible with improved contrast. - Highlights: ► Distinguishable anatomical structures features of rat kidney and rat brain are acquired with Sy-DEI in planar mode. ► Images of a small brain phantom and cylindrical phantom are acquired in tomography mode (Sy-DEI-CT) with contrast agents. ► Sy-DEI and Sy-DEI-CT techniques provide new source of information related to biological microanatomy.

  2. The analytical of radiochemical purity of tumor receptor imaging agent 99Tcm-octreotide

    International Nuclear Information System (INIS)

    Wang Xufu; Zuo Shuyao; Shao Wenbo; Wang Guoming; Sun Jianwen; Zhang Qin

    2003-01-01

    The radiochemical purity of tumor receptor imaging agent 99 Tc m -octreotide is measured by High Pressure Liquid Chromatography (HPLC) and two systems of chromatography combining method of silver stain. The results show that the radiochemical purity of 98 Tc m -octreotide measured by both methods are effective and correct. It can separate 99 Tc m -octreotide from other radioactive compositions correctly and effectively

  3. Identification of a Common Binding Mode for Imaging Agents to Amyloid Fibrils from Molecular Dynamics Simulations

    DEFF Research Database (Denmark)

    Skeby, Katrine Kirkeby; Sørensen, Jesper; Schiøtt, Birgit

    2013-01-01

    experimentally due to the insoluble nature of amyloid fibrils. This study uses molecular dynamics simulations to investigate the interactions between 13 aromatic amyloid imaging agents, entailing 4 different organic scaffolds, and a model of an amyloid fibril. Clustering analysis combined with free energy...

  4. Zirconia-doped nanoparticles: organic coating, polymeric entrapment and application as dual-imaging agents

    OpenAIRE

    Rebuttini, Valentina; Pucci, Andrea; Arosio, Paolo; Bai, Xue; Locatelli, Erica; Pinna, Nicola; Lascialfari, Alessandro; Franchini, Mauro Comes

    2013-01-01

    Zirconia nanoparticles doped with Eu3+, Tb3+ and Gd3+ ions have been synthesized following the benzyl alcohol route. The nanoparticles were coated with N-hydroxydodecanamide and encapsulated in PLGA-b-PEG-COOH nanomicelles. The magnetic and fluorescent properties of these hybrid nanocarriers were investigated, proving them to be potential dual-imaging contrast agents.

  5. A theranostic agent to enhance osteogenic and magnetic resonance imaging properties of calcium phosphate cements

    NARCIS (Netherlands)

    Ventura, M.; Sun, Y.; Cremers, S.; Borm, P.; Tahmasebi Birgani, Zeinab; Habibovic, Pamela; Heerschap, A.; van der Kraan, P.M.; Jansen, J.A.; Walboomers, X.F.

    2014-01-01

    With biomimetic biomaterials, like calcium phosphate cements (CPCs), non-invasive assessment of tissue regeneration is challenging. This study describes a theranostic agent (TA) to simultaneously enhance both imaging and osteogenic properties of such a bone substitute material. For this purpose,

  6. Synthesis and evaluation of three iodinated haloperidol derivatives as potential dopamine receptor imaging agents

    International Nuclear Information System (INIS)

    Hunter, D.H.; Strickland, L.A.; Zabel, P.L.

    1990-01-01

    Haloperidol, a neuroleptic which shows D-2 receptor affinity and selectivity, has been labelled primarily with positron emitting isotopes. The authors have synthesized three iodinated analogues of Haloperidol to investigate the possibility of an iodine-123 labelled agent for SPECT imaging. These compounds were obtained from the substitution of halogenated butyrophenones by halogenated arylpiperidols. In vitro and in vivo experiments will be discussed

  7. Amphetamines and pH-shift agents for brain imaging: Basic research and clinical results

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Winkler, C.

    1986-01-01

    This book contains 18 selections. Some of the titles are: Labelling of amphetamines with /sup 123/I: Receptors for amphetamines; New amphetamine derivatives; Potential new approaches for the development of brain imaging agents for single-photon applications; and IM SPECT with the pinhole collimator.

  8. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

    NARCIS (Netherlands)

    Temming, K; Molema, G; Kok, RJ

    2005-01-01

    During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to a(v)beta(3)-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to

  9. NaGdF4:Nd3+/Yb3+ Nanoparticles as Multimodal Imaging Agents

    Science.gov (United States)

    Pedraza, Francisco; Rightsell, Chris; Kumar, Ga; Giuliani, Jason; Monton, Car; Sardar, Dhiraj

    Medical imaging is a fundamental tool used for the diagnosis of numerous ailments. Each imaging modality has unique advantages; however, they possess intrinsic limitations. Some of which include low spatial resolution, sensitivity, penetration depth, and radiation damage. To circumvent this problem, the combination of imaging modalities, or multimodal imaging, has been proposed, such as Near Infrared Fluorescence imaging (NIRF) and Magnetic Resonance Imaging (MRI). Combining individual advantages, specificity and selectivity of NIRF with the deep penetration and high spatial resolution of MRI, it is possible to circumvent their shortcomings for a more robust imaging technique. In addition, both imaging modalities are very safe and minimally invasive. Fluorescent nanoparticles, such as NaGdF4:Nd3 +/Yb3 +, are excellent candidates for NIRF/MRI multimodal imaging. The dopants, Nd and Yb, absorb and emit within the biological window; where near infrared light is less attenuated by soft tissue. This results in less tissue damage and deeper tissue penetration making it a viable candidate in biological imaging. In addition, the inclusion of Gd results in paramagnetic properties, allowing their use as contrast agents in multimodal imaging. The work presented will include crystallographic results, as well as full optical and magnetic characterization to determine the nanoparticle's viability in multimodal imaging.

  10. Element-specific spectral imaging of multiple contrast agents: a phantom study

    Science.gov (United States)

    Panta, R. K.; Bell, S. T.; Healy, J. L.; Aamir, R.; Bateman, C. J.; Moghiseh, M.; Butler, A. P. H.; Anderson, N. G.

    2018-02-01

    This work demonstrates the feasibility of simultaneous discrimination of multiple contrast agents based on their element-specific and energy-dependent X-ray attenuation properties using a pre-clinical photon-counting spectral CT. We used a photon-counting based pre-clinical spectral CT scanner with four energy thresholds to measure the X-ray attenuation properties of various concentrations of iodine (9, 18 and 36 mg/ml), gadolinium (2, 4 and 8 mg/ml) and gold (2, 4 and 8 mg/ml) based contrast agents, calcium chloride (140 and 280 mg/ml) and water. We evaluated the spectral imaging performances of different energy threshold schemes between 25 to 82 keV at 118 kVp, based on K-factor and signal-to-noise ratio and ranked them. K-factor was defined as the X-ray attenuation in the K-edge containing energy range divided by the X-ray attenuation in the preceding energy range, expressed as a percentage. We evaluated the effectiveness of the optimised energy selection to discriminate all three contrast agents in a phantom of 33 mm diameter. A photon-counting spectral CT using four energy thresholds of 27, 33, 49 and 81 keV at 118 kVp simultaneously discriminated three contrast agents based on iodine, gadolinium and gold at various concentrations using their K-edge and energy-dependent X-ray attenuation features in a single scan. A ranking method to evaluate spectral imaging performance enabled energy thresholds to be optimised to discriminate iodine, gadolinium and gold contrast agents in a single spectral CT scan. Simultaneous discrimination of multiple contrast agents in a single scan is likely to open up new possibilities of improving the accuracy of disease diagnosis by simultaneously imaging multiple bio-markers each labelled with a nano-contrast agent.

  11. Hypoxic tumor environments exhibit disrupted collagen I fibers and low macromolecular transport.

    Directory of Open Access Journals (Sweden)

    Samata M Kakkad

    Full Text Available Hypoxic tumor microenvironments result in an aggressive phenotype and resistance to therapy that lead to tumor progression, recurrence, and metastasis. While poor vascularization and the resultant inadequate drug delivery are known to contribute to drug resistance, the effect of hypoxia on molecular transport through the interstitium, and the role of the extracellular matrix (ECM in mediating this transport are unexplored. The dense mesh of fibers present in the ECM can especially influence the movement of macromolecules. Collagen 1 (Col1 fibers form a key component of the ECM in breast cancers. Here we characterized the influence of hypoxia on macromolecular transport in tumors, and the role of Col1 fibers in mediating this transport using an MDA-MB-231 breast cancer xenograft model engineered to express red fluorescent protein under hypoxia. Magnetic resonance imaging of macromolecular transport was combined with second harmonic generation microscopy of Col1 fibers. Hypoxic tumor regions displayed significantly decreased Col1 fiber density and volume, as well as significantly lower macromolecular draining and pooling rates, than normoxic regions. Regions adjacent to severely hypoxic areas revealed higher deposition of Col1 fibers and increased macromolecular transport. These data suggest that Col1 fibers may facilitate macromolecular transport in tumors, and their reduction in hypoxic regions may reduce this transport. Decreased macromolecular transport in hypoxic regions may also contribute to poor drug delivery and tumor recurrence in hypoxic regions. High Col1 fiber density observed around hypoxic regions may facilitate the escape of aggressive cancer cells from hypoxic regions.

  12. Biodistribution and micro PET imaging of 18F-FECNT as a dopamine transporter imaging agent

    International Nuclear Information System (INIS)

    Chen Zhengping; Wang Songpei; Li Xiaomin; Liu Chunyi; Tang Jie; Lu Chunxiong; Pan Donghui; Xu Yuping; Yang Ming; Jiang Quanfu; Huang Hongbo; Zhou Xingqing

    2009-01-01

    Objective: 2β-carbomethoxy-3β-(4-corophenyl)-8-(2- 18 F-fluoroethyl) nortropane ( 18 F-FECNT) is a recently developed dopamine transporter (DAT) imaging agent. The aim of this study was to evaluate its brain biodistribution and to assess its usefulness in quantitation of DAT density in normal and hemiparkinsonian rats. Methods: Six groups of mice (5 mice each group) received 18 F-FECNT were sacrificed at indicated time post injection. Different brain regions (cortex, hippocampus, striatum, cerebellum) were removed, weighed, and countered. DAT blocking effect was investigated in mice pretreated with 2β-Carbomethoxy-3β-(4-fluorphenyl)tropane (β-CFT) at before 18 F-FECNT injection. MicroPET scans were performed in beth normal and unilaterally 6-hydroxydopamine-lesioned rats. Results: The brain uptake of 18 F-FECNT was 2.22, 1.20, 1.02, 0.78, 0.71, and 0.67 percent injection dose (%ID) at 5, 15, 30, 60, 120, and 180 min post injection. Radioactivity concentration of the striatum, the target region, was the highest in the brain regions and decreased quickly from 5 to 60 min and reached to background at 120 min of post injection. The striatum/cerebellum ratio was 2.56, 3.47, 2.78, 1.63, 0.97, and 0.88 at 5, 15, 30, 60, 120, and 180 min, respectively, post injection. The selective striatum uptake of 1 '8F-FECNT decreased dramatically to the background when the DAT was blocked with β-CFT. The striatum of normal rats in micro-PET exhibited symmetrical (left/right = 1.00 ± 0.05) and the highest uptake of radioactivity (striatum/cerebellum =2.18 ± 0. 16 at 5- 125 min, n =3). As for the hemiparkinsonian rats, nonsymmetrical [unlesioned striatum/cerebellum vs lesioned striatum/cerebellum = 2.01 ± 0.23 (n = 3) vs 1.04 ± 0. 05] and the high-est uptake of radioactivity were also noted. Conclusions: The results suggest that 18 F-FECNT rapidly pas-ses through blood-brain barrier and locates in stiatal region with high affinity and selectivity to DAT. It is a potential

  13. RNA aptamer probes as optical imaging agents for the detection of amyloid plaques.

    Directory of Open Access Journals (Sweden)

    Christian T Farrar

    Full Text Available Optical imaging using multiphoton microscopy and whole body near infrared imaging has become a routine part of biomedical research. However, optical imaging methods rely on the availability of either small molecule reporters or genetically encoded fluorescent proteins, which are challenging and time consuming to develop. While directly labeled antibodies can also be used as imaging agents, antibodies are species specific, can typically not be tagged with multiple fluorescent reporters without interfering with target binding, and are bioactive, almost always eliciting a biological response and thereby influencing the process that is being studied. We examined the possibility of developing highly specific and sensitive optical imaging agents using aptamer technology. We developed a fluorescently tagged anti-Aβ RNA aptamer, β55, which binds amyloid plaques in both ex vivo human Alzheimer's disease brain tissue and in vivo APP/PS1 transgenic mice. Diffuse β55 positive halos, attributed to oligomeric Aβ, were observed surrounding the methoxy-XO4 positive plaque cores. Dot blots of synthetic Aβ aggregates provide further evidence that β55 binds both fibrillar and non-fibrillar Aβ. The high binding affinity, the ease of probe development, and the ability to incorporate multiple and multimodal imaging reporters suggest that RNA aptamers may have complementary and perhaps advantageous properties compared to conventional optical imaging probes and reporters.

  14. Molecular Imaging Agents Specific for the Annulus Fibrosus of the Intervertebral Disk

    Directory of Open Access Journals (Sweden)

    Summer L. Gibbs-Strauss

    2010-05-01

    Full Text Available Low back pain is a prevalent medical condition that is difficult to diagnose and treat. Current imaging methods are unable to correlate pain reliably with spinal structures, and surgical removal of painful damaged or degenerating disks is technically challenging. A contrast agent specific for the intervertebral disk could assist in the detection, diagnosis, and surgical treatment of low back pain. The styryl pyridinium (FM fluorophores were characterized and structure-activity relationships between chemical structure and in vivo uptake were established. Two novel FM fluorophores with improved optical properties for imaging the intervertebral disks were synthesized and evaluated in mice, rats, and pigs. After a single systemic injection, eight of eight FM fluorophores provided high-contrast imaging of the trigeminal ganglia, whereas six of eight provided high-contrast imaging of the dorsal root ganglia. Unexpectedly, three of eight FM fluorophores provided high-contrast imaging of annulus fibrosus tissue of the intervertebral disks, confirmed histologically. We present the first known contrast agent specific for the intervertebral disks and identify the chemical structural motif that mediates uptake. FM fluorophores could be used for image-guided surgery to assist in the removal of intervertebral disk and lay the foundation for derivatives for magnetic resonance imaging and positron emission tomography.

  15. Experimental studies of the physiologic properties of technetium-99m agents: Myocardial transport of perfusion imaging agents

    International Nuclear Information System (INIS)

    Meerdink, D.J.; Leppo, J.A.

    1990-01-01

    The physiologic properties of new technetium-99m-labeled myocardial imaging agents (Tc-99m sestamibi, an isonitrile; and Tc-99m teboroxime, a boronic acid adduct of technetium dioxime) are discussed and compared to thallium-201 (Tl-201). Studies with isolated hearts, subcellular fractions and cell cultures indicate that Tc-99m sestamibi, Tc-99m teboroxime and Tl-201 do not share common transport or sequestration mechanisms. Although peak Tc-99m sestamibi myocardial extraction over time is about half that of Tl-201 at equivalent coronary blood flows, the amount of Tc-99m sestamibi that remains in the heart is similar to that of Tl-201 because of its higher retention efficiency. The high retention efficiency for Tc-99m sestamibi also results in minimal redistribution. In contrast, Tc-99m teboroxime myocardial extraction is higher than that of Tl-201, but its retention is less efficient, resulting in relatively rapid washout characteristics which may quickly result in tracer redistribution. During reperfusion after a no-flow period, Tc-99m sestamibi extraction and retention increase, but for Tc-99m teboroxime and Tl-201 these values tend to decrease. All tracers show adequate transport characteristics for perfusion imaging, and differences in transport and retention should lead to the development of new clinical protocols.27 references

  16. 19F labelled dextrans and antibodies as NMR imaging and spectroscopy agents

    International Nuclear Information System (INIS)

    Antich, P.P.; Kulkarni, P.V.

    1993-01-01

    A method is described of NMR imaging or spectroscopy, comprising the steps of administering to a living subject a 19 F labelled NMR agent, the NMR agent comprising (a) a transport polymer selected from the group consisting of dextran polymers and amino dextrans, having a molecular weight between approximately 100 d and 500 kd, and antibodies and fragments thereof, and (b) a 19F-containing sensor moiety selected from the group consisting of fluorinated alkyls, fluorinated acetates, fluoroaniline, and fluoroalkyl phosphonates, in an amount effective to provide a detectable NMR signal; and then detecting the 19 F NMR signal produced

  17. Uptake of perfusion imaging agents by transplanted hearts: an experimental study in rats

    International Nuclear Information System (INIS)

    Bergsland, J.; Carr, E.A. Jr.; Carroll, M.; Feldman, M.J.; Kung, H.; Wright, J.R.

    1989-01-01

    There is a need for a reliable noninvasive marker of rejection in transplanted hearts. Endomyocardial biopsy is now the universally accepted diagnostic method of choice, but the invasiveness of the procedure and the limited size of the sample obtained makes this method far from ideal. As coronary blood flow may be expected to decrease during acute rejection, there has been interest in thallium-201 chloride (T1), a perfusion marker, as an imaging agent for diagnosing cardiac rejection. Hexakis(t-butylisonitrile)-technetium (Tc-TBI) is a representative of a new class of radiopharmaceuticals proposed as perfusion markers. We have compared the uptake of these imaging agents in a rat model of cardiac transplantation. Uptake of Tc-TBI as well as of T1 was significantly lower in rejecting than in nonrejecting hearts. This change was found in both left (LV) and right (RV) ventricles. Allografts in animals treated with cyclosporine (CyA) showed less severe rejection and higher uptakes of both imaging agents as compared to unmodified rejection. Our results suggest that perfusion imaging with these radionuclides is a potentially useful approach to the problem of detecting allograft rejection

  18. The synthesis of radioiodinated carbohydrates and butyrothenones as potential imaging agents for computed tomography

    International Nuclear Information System (INIS)

    Waterhouse, R.N.

    1993-01-01

    Positron Emission tomography (PET) and Single Photon Emission Computed Tomography (SPECT) are two relatively new imaging techniques which allow for the non-invasive evaluation of biochemical processes in living subjects. Currently, SPECT is more widely accessible than PET, however, only a limited number of radiotracers have been successfully developed for imaging by SPECT. Two classes of radioiodinated compounds were developed as potential imaging agents for SPECT: (1) Radioiodinated carbohydrates for the assessment of glucose metabolism and (2) Radioiodinated butyrothienones for the evaluation of dopamine D 2 receptors in the brain. In both classes of compounds, the radioiodine was attached to an sp 2 hybridized carbon atom to provide radiotracers that were chemically and metabolically stable. Radioiodine incorporation was easily accomplished by radioiododestannylation of vinyl- and aryl-trialkylstannanes in the presence of an oxidizing agent. The incorporation of radioiodine into small molecules can have a significant effect on the biological activity of the resulting radiotracer because of the relatively large size and lipophilicity of the iodine atom. Preliminary evaluations of the effectiveness of the radioiodinated carbohydrates and butyrothienones as imaging agents are presented

  19. A naturally occurring contrast agent for OCT imaging of smokers' lung

    International Nuclear Information System (INIS)

    Yang Ying; Bagnaninchi, Pierre O; Whiteman, Suzanne C; Pittius, Daniel Gey van; Haj, Alicia J El; Spiteri, Monica A; Wang, Ruikang K

    2005-01-01

    Optical coherence tomography (OCT) offers great potential for clinical applications in terms of its cost, safety and real-time imaging capability. Improvement of its resolution for revealing sub-layers or sub-cellular components within a tissue will further widen its application. In this study we report that carbon pigment, which is frequently present in the lungs of smokers, could be used as a contrast agent to improve the OCT imaging of lung tissue. Carbon produced an intense bright OCT image at a relatively deep location. The parallel histopathological section analysis confirmed the presence of carbon pigment in such tissues. The underlying mechanism of the OCT image formation has been discussed based on a model system in which carbon particles were dispersed in agar gel. Calculations and in-depth intensity profiles of OCT revealed that higher refractive index particles with a size close to or smaller than the wavelength would greatly increase backscattering and generate a sharp contrast, while a particle size several times larger than the wavelength would absorb or obstruct the light path. The naturally occurring contrast agent could provide a diagnostic biomarker of lung tissue in smokers. Furthermore, carbon under such circumstances, can be used as an effective exogenous contrast agent, with which specific components or tissues exhibiting early tumour formation can be optically labelled to delineate the location and boundary, providing potential for early cancer detection and its treatment

  20. X-ray Scatter Imaging of Hepatocellular Carcinoma in a Mouse Model Using Nanoparticle Contrast Agents

    Science.gov (United States)

    Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; Wands, Jack R.; Rose-Petruck, Christoph

    2015-10-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. The enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

  1. Experimental design and instability analysis of coaxial electrospray process for microencapsulation of drugs and imaging agents.

    Science.gov (United States)

    Si, Ting; Zhang, Leilei; Li, Guangbin; Roberts, Cynthia J; Yin, Xiezhen; Xu, Ronald

    2013-07-01

    Recent developments in multimodal imaging and image-guided therapy requires multilayered microparticles that encapsulate several imaging and therapeutic agents in the same carrier. However, commonly used microencapsulation processes have multiple limitations such as low encapsulation efficiency and loss of bioactivity for the encapsulated biological cargos. To overcome these limitations, we have carried out both experimental and theoretical studies on coaxial electrospray of multilayered microparticles. On the experimental side, an improved coaxial electrospray setup has been developed. A customized coaxial needle assembly combined with two ring electrodes has been used to enhance the stability of the cone and widen the process parameter range of the stable cone-jet mode. With this assembly, we have obtained poly(lactide-co-glycolide) microparticles with fine morphology and uniform size distribution. On the theoretical side, an instability analysis of the coaxial electrified jet has been performed based on the experimental parameters. The effects of process parameters on the formation of different unstable modes have been studied. The reported experimental and theoretical research represents a significant step toward quantitative control and optimization of the coaxial electrospray process for microencapsulation of multiple drugs and imaging agents in multimodal imaging and image-guided therapy.

  2. Introduction to altitude/hypoxic training symposium.

    Science.gov (United States)

    Wilber, Randall L

    2007-09-01

    Altitude/hypoxic training has traditionally been an intriguing and controversial area of research and sport performance. This controversial aspect was evident recently in the form of scholarly debates in highly regarded professional journals, as well as the World Anti-Doping Agency's (WADA) consideration of placing "artificially-induced hypoxic conditions" on the 2007 Prohibited List of Substances/Methods. In light of the ongoing controversy surrounding altitude/hypoxic training, this symposium was organized with the following objectives in mind: 1) to examine the primary physiological responses and underlying mechanisms associated with altitude/hypoxic training, including the influence of genetic predisposition; 2) to present evidence supporting the effect of altitude/hypoxic acclimatization on both hematological and nonhematological markers, including erythrocyte volume, skeletal muscle-buffering capacity, hypoxic ventilatory response, and physiological efficiency/economy; 3) to evaluate the efficacy of several contemporary simulated altitude modalities and training strategies, including hypoxic tents, nitrogen apartments, and intermittent hypoxic exposure (IHE) or training, and to address the legal and ethical issues associated with the use of simulated altitude; and 4) to describe different altitude/hypoxic training strategies used by elite-level athletes, including Olympians and military special forces. In addressing these objectives, papers will be presented on the topics of: 1) effect of hypoxic "dose" on physiological responses and sea-level performance (Drs. Benjamin Levine and James Stray-Gundersen), 2) nonhematological mechanisms of improved performance after hypoxic exposure (Dr. Christopher Gore), 3) application of altitude/hypoxic training by elite athletes (Dr. Randall Wilber), and 4) military applications of hypoxic training (Dr. Stephen Muza).

  3. Evaluation of potential practical oral contrast agents for pediatric magnetic resonance imaging

    International Nuclear Information System (INIS)

    Bisset, G.S. III; Cincinnati Univ., OH; Children's Hospital Medical Center, Cincinnati, OH

    1989-01-01

    Development of a practical oral contrast agent for magnetic resonance imaging is necessary to improve differentiation of bowel from adjacent structures. In order to find a readily available, inexpensive, non-toxic, palatable solution for use in the pediatric population, several formulas, milk products and a common oral sedative were evaluated in vitro. T1, T2 and signal intensity measurements were performed on a 1.5 T system. Similac with standard iron proved to be a useful high signal intensity agent on multiple pulse sequences. Early in vivo experience in four normal volunteers indicates that this agent provides excellent delineation of the stomach and duodenum from contiguous viscera. Distal small bowel visualization is less predictabel. Further clinical trials should confirm the utility of this solution, which contains a combination of iron salts and paramagnetic metallic ions. (orig.)

  4. Current status of superparamagnetic iron oxide contrast agents for liver magnetic resonance imaging.

    Science.gov (United States)

    Wang, Yi-Xiang J

    2015-12-21

    Five types of superparamagnetic iron oxide (SPIO), i.e. Ferumoxides (Feridex(®) IV, Berlex Laboratories), Ferucarbotran (Resovist(®), Bayer Healthcare), Ferumoxtran-10 (AMI-227 or Code-7227, Combidex(®), AMAG Pharma; Sinerem(®), Guerbet), NC100150 (Clariscan(®), Nycomed,) and (VSOP C184, Ferropharm) have been designed and clinically tested as magnetic resonance contrast agents. However, until now Resovist(®) is current available in only a few countries. The other four agents have been stopped for further development or withdrawn from the market. Another SPIO agent Ferumoxytol (Feraheme(®)) is approved for the treatment of iron deficiency in adult chronic kidney disease patients. Ferumoxytol is comprised of iron oxide particles surrounded by a carbohydrate coat, and it is being explored as a potential imaging approach for evaluating lymph nodes and certain liver tumors.

  5. Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

    Directory of Open Access Journals (Sweden)

    Estelrich J

    2015-03-01

    Full Text Available Joan Estelrich,1,2 María Jesús Sánchez-Martín,1 Maria Antònia Busquets1,2 1Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Catalonia, Spain; 2Institut de Nanociència I Nanotecnologia (IN2UB, Barcelona, Catalonia, SpainAbstract: Magnetic resonance imaging (MRI has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times (T1, spin–lattice relaxation and T2, spin–spin relaxation of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents are administered prior to the scanning. Shortening T1 and T2 increases the corresponding relaxation rates, 1/T1 and 1/T2, producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T2-weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions, providing positive contrast in T1-weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of

  6. Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy

    International Nuclear Information System (INIS)

    Daldrup-Link, Heike E.; Rudelius, Martina; Piontek, Guido; Schlegel, Juergen; Metz, Stephan; Settles, Marcus; Rummeny, Ernst J.; Pichler, Bernd; Heinzmann, Ulrich; Oostendorp, Robert A.J.

    2004-01-01

    The purpose of this study was to assess the feasibility of use of gadophrin-2 to trace intravenously injected human hematopoietic cells in athymic mice, employing magnetic resonance (MR) imaging, optical imaging (OI), and fluorescence microscopy. Mononuclear peripheral blood cells from GCSF-primed patients were labeled with gadophrin-2 (Schering AG, Berlin, Germany), a paramagnetic and fluorescent metalloporphyrin, using established transfection techniques with cationic liposomes. The labeled cells were evaluated in vitro with electron microscopy and inductively coupled plasma atomic emission spectrometry. Then, 1 x 10 6 -3 x 10 8 labeled cells were injected into 14 nude Balb/c mice and the in vivo cell distribution was evaluated with MR imaging and OI before and 4, 24, and 48 h after intravenous injection (p.i.). Five additional mice served as controls: three mice were untreated controls and two mice were investigated after injection of unlabeled cells. The contrast agent effect was determined quantitatively for MR imaging by calculating signal-to-noise-ratio (SNR) data. After completion of in vivo imaging studies, fluorescence microscopy of excised organs was performed. Intracellular cytoplasmatic uptake of gadophrin-2 was confirmed by electron microscopy. Spectrometry determined an uptake of 31.56 nmol Gd per 10 6 cells. After intravenous injection, the distribution of gadophrin-2 labeled cells in nude mice could be visualized by MR, OI, and fluorescence microscopy. At 4 h p.i., the transplanted cells mainly distributed to lung, liver, and spleen, and 24 h p.i. they also distributed to the bone marrow. Fluorescence microscopy confirmed the distribution of gadophrin-2 labeled cells to these target organs. Gadophrin-2 is suited as a bifunctional contrast agent for MR imaging, OI, and fluorescence microscopy and may be used to combine the advantages of each individual imaging modality for in vivo tracking of intravenously injected hematopoietic cells. (orig.)

  7. Automated synthesis of the estrogen receptors imaging agent 18F-FES

    International Nuclear Information System (INIS)

    Guo Shen; Chen Guobao; Dai Hongfeng; Lin Meifu; Chen Wenxin

    2011-01-01

    Objective: 18 F-16α-17β-fluoroestradiol ( 18 F-FES), an estrogen receptors imaging agent, is synthesized with Tracerlab FX FN system. Methods: 18 F-FES is obtained by two steps reactions, including the nucleophilic displacement reaction of no-carrier-added 18 F-fluoride with 3-O-methoxymethyl-16, 17-O-sulfuryl-16-epiesteriol, then the intermediate is evaporated and hydrolyzed with HCI and finally gives 18 F-FES. Results: The synthesis of 18 F-FES can be completed in about 80 min.The radiochemical yield and radio-chemical purity are about 10% and 95% respectively. Conclusion: The procedure of synthesis is simple and automatical. 18 F-FES has an extremely low toxicity, which suggests that 18 F-FES may be a safe, a nd effective estrogen receptors imaging agent. (authors)

  8. Semiconducting polymer dot as a highly effective contrast agent for photoacoustic imaging

    Science.gov (United States)

    Yuan, Zhen; Zhang, Jian

    2018-02-01

    In this study, we developed a novel PIID-DTBT based semiconducting polymer dots (Pdots) that have broad and strong optical absorption in the visible-light region (500 nm - 700 nm). Gold nanoparticles (GNPs) and gold nanorods (GNRs) that have been verified as an excellent photoacoustic contrast agent were compared with Pdots based on photoacoustic imaging method. Both ex vivo and in vivo experiment demonstrated Pdots have a better photoacoustic conversion efficiency at 532 nm than GNPs and similar photoacoustic performance with GNRs at 700 nm at the same mass concentration. Our work demonstrates the great potential of Pdots as a highly effective contrast agent for precise localization of lesions relative to the blood vessels based on photoacoustic tomography imaging.

  9. Automatic spectral imaging protocol selection and iterative reconstruction in abdominal CT with reduced contrast agent dose: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peijie; Liu, Jie; Chai, Yaru; Yan, Xiaopeng; Gao, Jianbo; Dong, Junqiang [The First Affiliated Hospital of Zhengzhou University, Department of Radiology, Zhengzhou, Henan Province (China)

    2017-01-15

    To evaluate the feasibility, image quality, and radiation dose of automatic spectral imaging protocol selection (ASIS) and adaptive statistical iterative reconstruction (ASIR) with reduced contrast agent dose in abdominal multiphase CT. One hundred and sixty patients were randomly divided into two scan protocols (n = 80) each; protocol A, 120 kVp/450 mgI/kg, filtered back projection algorithm (FBP); protocol B, spectral CT imaging with ASIS and 40 to 70 keV monochromatic images generated per 300 mgI/kg, ASIR algorithm. Quantitative parameters (image noise and contrast-to-noise ratios [CNRs]) and qualitative visual parameters (image noise, small structures, organ enhancement, and overall image quality) were compared. Monochromatic images at 50 keV and 60 keV provided similar or lower image noise, but higher contrast and overall image quality as compared with 120-kVp images. Despite the higher image noise, 40-keV images showed similar overall image quality compared to 120-kVp images. Radiation dose did not differ between the two protocols, while contrast agent dose in protocol B was reduced by 33 %. Application of ASIR and ASIS to monochromatic imaging from 40 to 60 keV allowed contrast agent dose reduction with adequate image quality and without increasing radiation dose compared to 120 kVp with FBP. (orig.)

  10. Automatic spectral imaging protocol selection and iterative reconstruction in abdominal CT with reduced contrast agent dose: initial experience

    International Nuclear Information System (INIS)

    Lv, Peijie; Liu, Jie; Chai, Yaru; Yan, Xiaopeng; Gao, Jianbo; Dong, Junqiang

    2017-01-01

    To evaluate the feasibility, image quality, and radiation dose of automatic spectral imaging protocol selection (ASIS) and adaptive statistical iterative reconstruction (ASIR) with reduced contrast agent dose in abdominal multiphase CT. One hundred and sixty patients were randomly divided into two scan protocols (n = 80) each; protocol A, 120 kVp/450 mgI/kg, filtered back projection algorithm (FBP); protocol B, spectral CT imaging with ASIS and 40 to 70 keV monochromatic images generated per 300 mgI/kg, ASIR algorithm. Quantitative parameters (image noise and contrast-to-noise ratios [CNRs]) and qualitative visual parameters (image noise, small structures, organ enhancement, and overall image quality) were compared. Monochromatic images at 50 keV and 60 keV provided similar or lower image noise, but higher contrast and overall image quality as compared with 120-kVp images. Despite the higher image noise, 40-keV images showed similar overall image quality compared to 120-kVp images. Radiation dose did not differ between the two protocols, while contrast agent dose in protocol B was reduced by 33 %. Application of ASIR and ASIS to monochromatic imaging from 40 to 60 keV allowed contrast agent dose reduction with adequate image quality and without increasing radiation dose compared to 120 kVp with FBP. (orig.)

  11. Highly stabilized gadolinium chelates functionalized on metal nanoparticles as magnetic resonance imaging contrast agent

    Science.gov (United States)

    Siddiqui, Talha S.

    Magnetic resonance imaging (MRI) is a non-invasive method for imaging and diagnosing tissue damage, organ function and the vascular system. Magnevist(TM) a complex of diethylenetriaminepentaacetic acid (DTPA) and Gd3+ is a clinically approved contrast agent for MRI. A derivative of DTPA was formed by the addition of two cysteine groups (DTPA-L-Cys) through amide linkage. The Gd complex of this ligand bonds with the silver surfaces through the cysteine thiols. GdDTPA-L-Cys was bound to ˜10nm diameter Ag nanoparticles for use as a multifunctional MRI contrast agent. The ligand and complex were characterized by 1H and 13C NMR, ESI-MS and IR spectroscopy. The silver construct was characterized by TEM, TGA and UV-Vis absorption spectra. The per metal complex r1 relaxivity of GdDTPA-L-Cys{Ag} greater than that of Magnavist(TM) with the same molarity for both compounds. The synthesis of a DTPA derivative is described that allows it to bind to silver or gold nanoparticles through a single thiol linkage (DTPASH). The resulting Gd complex, GdDTPASH, was bound to Ag nanoparticles to create a single monolayer on the surface. The construct was further stabilized in buffered solution with the addition of a thiolated PEG chain. The highly stabilized nanoparticle construct delivers a high payload of Gd compelex and is an effective T1 brightening agent. The production of this type of construct opens the way for engineered multimodal MRI contrast agents.

  12. Optical-based molecular imaging: contrast agents and potential medical applications

    International Nuclear Information System (INIS)

    Bremer, Christoph; Ntziachristos, Vasilis; Weissleder, Ralph

    2003-01-01

    Laser- and sensitive charge-coupled device technology together with advanced mathematical modelling of photon propagation in tissue has prompted the development of novel optical imaging technologies. Fast surface-weighted imaging modalities, such as fluorescence reflectance imaging (FRI) and 3D quantitative fluorescence-mediated tomography have now become available [1, 2]. These technical advances are paralleled by a rapid development of a whole range of new optical contrasting strategies, which are designed to generate molecular contrast within a living organism. The combination of both, technical advances of light detection and the refinement of optical contrast media, finally yields a new spectrum of tools for in vivo molecular diagnostics. Whereas the technical aspects of optical imaging are covered in more detail in a previous review article in ''European Radiology'' [3], this article focuses on new developments in optical contrasting strategies and design of optical contrast agents for in vivo diagnostics. (orig.)

  13. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    International Nuclear Information System (INIS)

    Ayyala, Rama S.; Teot, Lisa A.; Perez Rossello, Jeanette M.

    2017-01-01

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

  14. Evaluation of 18F-labeled icotinib derivatives as potential PET agents for tumor imaging

    International Nuclear Information System (INIS)

    Hongyu Ren; Hongyu Ning; Jin Chang; Mingxia Zhao; Yong He; Yan Chong; Chuanmin Qi

    2016-01-01

    In this study, three 18 F-labeled crown ether fused anilinoquinazoline derivatives ([ 18 F]11a-c) were synthesized and evaluated as potential tumor imaging probes. The biodistribution results of [ 18 F]11b were good. Compared with [ 18 F]-fludeoxyglucose and l-[ 18 F]-fluoroethyltyrosine in the same animal model, [ 18 F]11b had better tumor/brain, tumor/muscle, and tumor/blood uptake ratios. Overall, these results suggest that [ 18 F]11b is promising as a tumor imaging agent for positron emission tomography. (author)

  15. Evaluation of /sup 201/TlCl and delayed scan for thyroid imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Tatsuyoshi; Harada, Taneichi; Takahashi, Tatsuo; Senoo, Tsuneaki; Ohtsuka, Nobuaki; Ito, Yasuhiko [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    1982-11-01

    The results of 189 patients with nodular goiter by imaging with /sup 201/TlCl following with sup(99m)TcO/sub 4//sup -/ was presented. Accumulation of /sup 201/TlCl to the corresponding area was observed in 85.5% of cancer, 62.2% of adenoma, 42.5% of adenomatous goiter, and the usefulness of /sup 201/TlCl (early scan) for thyroid imaging agent was recognized. On the other hand, delayed scan for purpose of differentiation from benign to malignant was also performed. However, no significant differences were obtained.

  16. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ayyala, Rama S. [Morgan Stanley Children' s Hospital, Department of Radiology, Columbia University Medical Center, New York, NY (United States); Teot, Lisa A. [Boston Children' s Hospital, Department of Pathology, Harvard Medical School, Boston, MA (United States); Perez Rossello, Jeanette M. [Boston Children' s Hospital, Department of Radiology, Harvard Medical School, Boston, MA (United States)

    2017-04-15

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

  17. Radiolabeled adrenergic neuron-blocking agents: Adrenomedullary imaging with [131I]iodobenzylguanidine

    International Nuclear Information System (INIS)

    Wieland, D.M.; Wu, J.; Brown, L.E.; Mangner, T.J.; Swanson, D.P.; Beierwaltes, W.H.

    1980-01-01

    The tissue distributions of three radioiodinated neuron-blocking agents have been determined in dogs. Iodine-125-labeled meta- and para-iodobenzylguanidines show a striking affinity for, and retention in, the adrenal medulla. Peak concentrations of the two isomers exceed those of previously reported adrenophilic compounds. High myocardial concentrations were also observed at early time intervals. Images of the dog's adrenal medullae have been obtained with para[ 131 I]-iodobenzylguanidine

  18. Pharmacological studies of dopamine transporter imaging agent 125/131I-β-CIT

    International Nuclear Information System (INIS)

    Ding Shiyu; Zhou Xiang; Chen Zhengping; Wu Chunying; Lin Yansong; Ji Shuren; Lu Chunxiong; Fang Ping; Tang Jun; Wang Feng

    2001-01-01

    To prepare 125/131 I-β-CIT (2β-carbomethoxy-3β-(4-iodophenyl) tropane) as an imaging agent for dopamine transporter (DAT), the labelling method from tributylstannyl precursor with peracetic acid has been reported. The radiochemical purity (RCP) of the labelled compound was over 95% determined by HPLC and TLC. The stability, partition coefficients were also determined. The pharmacological studies of the imaging agent were performed in rats, mice, rabbits and normal monkey. The ligand showed preferable uptake in brain (1.9% ID/organ in rats and 4.5% ID/organ in mice at 5 min). The ratios of striatum/cerebellum, hippocampus/cerebellum and cortex/cerebellum were 28.9, 3.97 and 4.75 at 6 h in rats, and 8.52, 2.99 and 3.06 at 6 h in mice, respectively. In monkey brain imaging the ratios of striatum/frontal cortex (ST/FC) and striatum/occipital cortex (ST/OC) were 5.14 and 5.97 at 4h, respectively. All of above showed the high affinity of the ligand to DAT. The compound was primarily metabolized in liver because the hepatic uptake was much higher than other organs (75.4% ID/organ at 18h). The half-life of blood elimination was 5 min. The dose received by mice was 2500 times as high as that received by human in the test of undue toxicity, which evaluated the safety of the agent. All the results suggest that β-CIT can be used as a potential DAT imaging agent

  19. Transforming a Targeted Porphyrin Theranostic Agent into a PET Imaging Probe for Cancer

    Directory of Open Access Journals (Sweden)

    Jiyun Shi, Tracy W.B. Liu, Juan Chen, David Green, David Jaffray, Brian C. Wilson, Fan Wang, Gang Zheng

    2011-01-01

    Full Text Available Porphyrin based photosensitizers are useful agents for photodynamic therapy (PDT and fluorescence imaging of cancer. Porphyrins are also excellent metal chelators forming highly stable metallo-complexes making them efficient delivery vehicles for radioisotopes. Here we investigated the possibility of incorporating 64Cu into a porphyrin-peptide-folate (PPF probe developed previously as folate receptor (FR targeted fluorescent/PDT agent, and evaluated the potential of turning the resulting 64Cu-PPF into a positron emission tomography (PET probe for cancer imaging. Noninvasive PET imaging followed by radioassay evaluated the tumor accumulation, pharmacokinetics and biodistribution of 64Cu-PPF. 64Cu-PPF uptake in FR-positive tumors was visible on small-animal PET images with high tumor-to-muscle ratio (8.88 ± 3.60 observed after 24 h. Competitive blocking studies confirmed the FR-mediated tracer uptake by the tumor. The ease of efficient 64Cu-radiolabeling of PPF while retaining its favorable biodistribution, pharmacokinetics and selective tumor uptake, provides a robust strategy to transform tumor-targeted porphyrin-based photosensitizers into PET imaging probes.

  20. Evaluation of chirp reversal power modulation sequence for contrast agent imaging

    International Nuclear Information System (INIS)

    Novell, A; Sennoga, CA; Escoffre, JM; Chaline, J; Bouakaz, A

    2014-01-01

    Over the last decade, significant research effort has been focused on the use of chirp for contrast agent imaging because chirps are known to significantly increase imaging contrast-to-noise ratio (CNR). New imaging schemes, such as chirp reversal (CR), have been developed to improve contrast detection by increasing non-linear microbubble responses. In this study we evaluated the contrast enhancement efficiency of various chirped imaging sequences in combination with well-established imaging schemes such as power modulation (PM) and pulse inversion (PI). The imaging schemes tested were implemented on a fully programmable open scanner and evaluated by ultrasonically scanning (excitation frequency of 2.5 MHz; amplitude of 350 kPa) a tissue-mimicking flow phantom comprising a 4 mm diameter tube through which aqueous dispersions (dilution fraction of 1/2000) of the commercial ultrasound contrast agent, SonoVue ® were continuously circulated. The recovery of non-linear microbubble responses after chirp compression requires the development and the optimization of a specific filter. A compression filter was therefore designed and used to compress and extract several non-linear components from the received microbubble responses. The results showed that using chirps increased the image CNR by approximately 10 dB, as compared to conventional Gaussian apodized sine burst excitation but degraded the axial resolution by a factor of 1.4, at −3 dB. We demonstrated that the highest CNR and contrast-to-noise ratio (CTR) were achievable when CR was combined with PM as compared to other imaging schemes such as PI. (paper)

  1. Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery

    Directory of Open Access Journals (Sweden)

    Vera ePaefgen

    2015-09-01

    Full Text Available Ultrasound is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents. There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular contrast agents enable functional analyses, e.g. to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles’ shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by ultrasound pulses to locally release the entrapped agent. Recent studies show that ultrasound contrast agents are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of ultrasound contrast agents and introduces the current clinical applications of contrast-enhanced ultrasound. Additionally, an overview of the recent developments in ultrasound probe design for functional and molecular diagnosis as well as for drug delivery is given.

  2. The fabrication of novel nanobubble ultrasound contrast agent for potential tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Xing Zhanwen; Ke Hengte; Yue Xiuli; Dai Zhifei [Nanobiotechnology Division, State Key Laboratory of Urban Water Resources and Environment, School of Sciences, Harbin Institute of Technology, Harbin 150080 (China); Wang Jinrui; Zhao Bo [Department of Ultrasonography, Peking University Third Hospital, Beijing 100083 (China); Liu Jibin, E-mail: zhifei.dai@hit.edu.cn, E-mail: ji-bin.liu@jefferson.edu [Ultrasound Research and Education Institute, Thomas Jefferson University, Philadelphia, PA 19107 (United States)

    2010-04-09

    Novel biocompatible nanobubbles were fabricated by ultrasonication of a mixture of Span 60 and polyoxyethylene 40 stearate (PEG40S) followed by differential centrifugation to isolate the relevant subpopulation from the parent suspensions. Particle sizing analysis and optical microscopy inspection indicated that the freshly generated micro/nanobubble suspension was polydisperse and the size distribution was bimodal with large amounts of nanobubbles. To develop a nano-sized contrast agent that is small enough to leak through tumor pores, a fractionation to extract smaller bubbles by variation in the time of centrifugation at 20g (relative centrifuge field, RCF) was suggested. The results showed that the population of nanobubbles with a precisely controlled mean diameter could be sorted from the initial polydisperse suspensions to meet the specified requirements. The isolated bubbles were stable over two weeks under the protection of perfluoropropane gas. The acoustic behavior of the nano-sized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. Given the broad spectrum of potential clinical applications, the nano-sized contrast agent may provide a versatile adjunct for ultrasonic imaging enhancement and/or treatment of tumors.

  3. The fabrication of novel nanobubble ultrasound contrast agent for potential tumor imaging

    International Nuclear Information System (INIS)

    Xing Zhanwen; Ke Hengte; Yue Xiuli; Dai Zhifei; Wang Jinrui; Zhao Bo; Liu Jibin

    2010-01-01

    Novel biocompatible nanobubbles were fabricated by ultrasonication of a mixture of Span 60 and polyoxyethylene 40 stearate (PEG40S) followed by differential centrifugation to isolate the relevant subpopulation from the parent suspensions. Particle sizing analysis and optical microscopy inspection indicated that the freshly generated micro/nanobubble suspension was polydisperse and the size distribution was bimodal with large amounts of nanobubbles. To develop a nano-sized contrast agent that is small enough to leak through tumor pores, a fractionation to extract smaller bubbles by variation in the time of centrifugation at 20g (relative centrifuge field, RCF) was suggested. The results showed that the population of nanobubbles with a precisely controlled mean diameter could be sorted from the initial polydisperse suspensions to meet the specified requirements. The isolated bubbles were stable over two weeks under the protection of perfluoropropane gas. The acoustic behavior of the nano-sized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. Given the broad spectrum of potential clinical applications, the nano-sized contrast agent may provide a versatile adjunct for ultrasonic imaging enhancement and/or treatment of tumors.

  4. The fabrication of novel nanobubble ultrasound contrast agent for potential tumor imaging

    Science.gov (United States)

    Xing, Zhanwen; Wang, Jinrui; Ke, Hengte; Zhao, Bo; Yue, Xiuli; Dai, Zhifei; Liu, Jibin

    2010-04-01

    Novel biocompatible nanobubbles were fabricated by ultrasonication of a mixture of Span 60 and polyoxyethylene 40 stearate (PEG40S) followed by differential centrifugation to isolate the relevant subpopulation from the parent suspensions. Particle sizing analysis and optical microscopy inspection indicated that the freshly generated micro/nanobubble suspension was polydisperse and the size distribution was bimodal with large amounts of nanobubbles. To develop a nano-sized contrast agent that is small enough to leak through tumor pores, a fractionation to extract smaller bubbles by variation in the time of centrifugation at 20g (relative centrifuge field, RCF) was suggested. The results showed that the population of nanobubbles with a precisely controlled mean diameter could be sorted from the initial polydisperse suspensions to meet the specified requirements. The isolated bubbles were stable over two weeks under the protection of perfluoropropane gas. The acoustic behavior of the nano-sized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. Given the broad spectrum of potential clinical applications, the nano-sized contrast agent may provide a versatile adjunct for ultrasonic imaging enhancement and/or treatment of tumors.

  5. Experimental study of 99Tcm-tri-peptide as a novel tumor imaging agent

    International Nuclear Information System (INIS)

    Xie Wenhui; Cai Xiaojia; Liu Ciyi; Zeng Jun; Zhang Lihua; Lei Bei; Huang Gang

    2011-01-01

    Objective: To evaluate 99 Tc m -Arg-Glu-Ser ( 99 Tc m -RES) as a potential tumor imaging agent. Methods: RES was synthesized using solid phase peptide synthesis. The optimal labeling conditions of RES were determined under different reagents and reacting temperatures using SnC1 2 as reducing agent.The biodistribution of 99 Tc m -RES was studied in nude mice bearing human lung cancer A549. Results: The radiochemical purity of 99 Tc m -RES was up to 85% and the radiochemical purity was 75% ever after 6 h at room temperature. The tumor uptake of 99 Tc m -RES was obvious and the radioactivity ratios of tumor/blood, tumor/heart, tumor/liver, tumor/lung, tumor/spleen and tumor/muscle were 5.31, 1.88, 1.57, 3.58, 4.16 and 5.92, respectively at 6 h after 99 Tc m -RES injection. Gamma camera imaging showed that tumor uptake of 99 Tc m -RES was negative in rabbits with inflammatory mass but positive in those bearing tumor. The radioactivity ratio of tumor/inflammation was 3.12 at 6 h after injection. Conclusion: 99 Tc m -RES might possibly become a potential tumor imaging agent. (authors)

  6. MRI contrast agent for molecular imaging of the HER2/neu receptor using targeted magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira; Rajabi, Hossein, E-mail: hrajabi@modares.ac.ir [Tarbiat Modares University, Department of Medical Physics (Iran, Islamic Republic of); Babaei, Mohammad Hossein [Nuclear Science and Technology Research Institute, Department of Radioisotope (Iran, Islamic Republic of); Akhlaghpoor, Shahram [Sina Hospital, Tehran Medical University, Noor Medical Imaging Center (Iran, Islamic Republic of)

    2011-06-15

    In this study, Trastuzumab modified Magnetic Nanoparticles (TMNs) were prepared as a new contrast agent for detecting HER2 (Human epidermal growth factor receptor-2) expression tumors by magnetic resonance imaging (MRI). TMNs were prepared based on iron oxide nanoparticles core and Trastuzumab modified dextran coating. The TMNs core and hydrodynamic size were determined by transmission electron microscopy and dynamic light scattering. TMNs stability and cytotoxicity were investigated. The ability of TMNs for HER2 detection were evaluated in breast carcinoma cell lines (SKBr3 and MCF7 cells) and tumor-bearing mice by MRI and iron uptake determination. The particles core and hydrodynamic size were 9 {+-} 2.5 and 41 {+-} 15 nm (size range: 15-87 nm), respectively. The molar antibody/nanoparticle ratio was 3.1-3.5. TMNs were non-toxic to the cells below the 30 {mu}g (Fe)/mL concentration and good stable up to 8 weeks in PBS buffer. TMNs could detect HER2 oncogenes in the cells surface with imagable contrast by MRI. The invivo study in mice bearing tumors indicated that TMNs possessed a good diagnostic ability as HER2 specific contrast agent by MRI. TMNs were demonstrated to be able to selectively accumulate in the tumor cells, with a proper signal enhancement in MRI T2 images. So, the complex may be considered for further investigations as an MRI contrast agent for detection of HER2 expression tumors in human.

  7. Automatic spectral imaging protocol selection and iterative reconstruction in abdominal CT with reduced contrast agent dose: initial experience.

    Science.gov (United States)

    Lv, Peijie; Liu, Jie; Chai, Yaru; Yan, Xiaopeng; Gao, Jianbo; Dong, Junqiang

    2017-01-01

    To evaluate the feasibility, image quality, and radiation dose of automatic spectral imaging protocol selection (ASIS) and adaptive statistical iterative reconstruction (ASIR) with reduced contrast agent dose in abdominal multiphase CT. One hundred and sixty patients were randomly divided into two scan protocols (n = 80 each; protocol A, 120 kVp/450 mgI/kg, filtered back projection algorithm (FBP); protocol B, spectral CT imaging with ASIS and 40 to 70 keV monochromatic images generated per 300 mgI/kg, ASIR algorithm. Quantitative parameters (image noise and contrast-to-noise ratios [CNRs]) and qualitative visual parameters (image noise, small structures, organ enhancement, and overall image quality) were compared. Monochromatic images at 50 keV and 60 keV provided similar or lower image noise, but higher contrast and overall image quality as compared with 120-kVp images. Despite the higher image noise, 40-keV images showed similar overall image quality compared to 120-kVp images. Radiation dose did not differ between the two protocols, while contrast agent dose in protocol B was reduced by 33 %. Application of ASIR and ASIS to monochromatic imaging from 40 to 60 keV allowed contrast agent dose reduction with adequate image quality and without increasing radiation dose compared to 120 kVp with FBP. • Automatic spectral imaging protocol selection provides appropriate scan protocols. • Abdominal CT is feasible using spectral imaging and 300 mgI/kg contrast agent. • 50-keV monochromatic images with 50 % ASIR provide optimal image quality.

  8. OUTCOMES in CHILDHOOD FOLLOWING THERAPEUTIC HYPOTHERMIA for NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE)

    Science.gov (United States)

    Natarajan, Girija; Pappas, Athina; Shankaran, Seetha

    2017-01-01

    In this chapter we review the childhood outcomes of neonates with birth depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children prior to the era of hypothermia for neuroprotection will first be summarized, followed by discussion of results from randomized controlled trials of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy. The predictors of outcome in childhood following neonatal HIE using clinical and imaging biomarkers following hypothermia therapy will be described. PMID:27863707

  9. Outcomes in childhood following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE).

    Science.gov (United States)

    Natarajan, Girija; Pappas, Athina; Shankaran, Seetha

    2016-12-01

    In this article, we review the childhood outcomes of neonates with birth depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children prior to the era of hypothermia for neuroprotection will first be summarized, followed by discussion of results from randomized controlled trials of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy. The predictors of outcome in childhood following neonatal HIE using clinical and imaging biomarkers following hypothermia therapy will be described. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Biodegradable polymer based theranostic agents for photoacoustic imaging and cancer therapy

    Science.gov (United States)

    Wang, Yan J.; Strohm, Eric M.; Kolios, Michael C.

    2016-03-01

    In this study, multifunctional theranostic agents for photoacoustic (PA), ultrasound (US), fluorescent imaging, and for therapeutic drug delivery were developed and tested. These agents consisted of a shell made from a biodegradable Poly(lactide-co-glycolic acid) (PLGA) polymer, loaded with perfluorohexane (PFH) liquid and gold nanoparticles (GNPs) in the core, and lipophilic carbocyanines fluorescent dye DiD and therapeutic drug Paclitaxel (PAC) in the shell. Their multifunctional capacity was investigated in an in vitro study. The PLGA/PFH/DiD-GNPs particles were synthesized by a double emulsion technique. The average PLGA particle diameter was 560 nm, with 50 nm diameter silica-coated gold nano-spheres in the shell. MCF7 human breast cancer cells were incubated with PLGA/PFH/DiDGNPs for 24 hours. Fluorescent and PA images were recorded using a fluorescent/PA microscope using a 1000 MHz transducer and a 532 nm pulsed laser. For the particle vaporization and drug delivery test, MCF7 cells were incubated with the PLGA/PFH-GNPs-PAC or PLGA/PFH-GNPs particles for 6, 12 and 24 hours. The effects of particle vaporization and drug delivery inside the cells were examined by irradiating the cells with a laser fluence of 100 mJ/cm2, and cell viability quantified using the MTT assay. The PA images of MCF7 cells containing PLGA/PFH/DiD-GNPs were spatially coincident with the fluorescent images, and confirmed particle uptake. After exposure to the PLGA/PFHGNP- PAC for 6, 12 and 24 hours, the cell survival rate was 43%, 38%, and 36% respectively compared with the control group, confirming drug delivery and release inside the cells. Upon vaporization, cell viability decreased to 20%. The particles show potential as imaging agents and drug delivery vehicles.

  11. Colorectal liver metastases: contrast agent diffusion coefficient for quantification of contrast enhancement heterogeneity at MR imaging.

    Science.gov (United States)

    Jia, Guang; O'Dell, Craig; Heverhagen, Johannes T; Yang, Xiangyu; Liang, Jiachao; Jacko, Richard V; Sammet, Steffen; Pellas, Theodore; Cole, Patricia; Knopp, Michael V

    2008-09-01

    To describe and determine the reproducibility of a simplified model to quantitatively measure heterogeneous intralesion contrast agent diffusion in colorectal liver metastases. This HIPAA-compliant retrospective study received institutional review board approval, and written informed consent was obtained from 14 patients (mean age, 61 years +/- 9 [standard deviation]; range, 41-78 years), including 10 men (mean age, 65 years +/- 8; range, 47-78 years) and four women (mean age, 54 years +/- 9; range, 41-59 years), with colorectal liver metastases. Magnetic resonance (MR) imaging was performed twice (first baseline MR image [B(1)] and second baseline MR image [B(2)]) in a single target lesion prior to therapy. Dynamic contrast material-enhanced MR imaging was performed by using a saturation-recovery fast gradient-echo sequence. A simplified contrast agent diffusion model was proposed, and a contrast agent diffusion coefficient (CDC) was calculated. The reproducibility of the CDC measurement was evaluated by using the Bland-Altman plot and a linear regression model. The mean CDC was 0.22 mm(2)/sec (range, 0.01-0.73 mm(2)/sec) on B(1) and 0.24 mm(2)/sec (range, 0.01-0.71 mm(2)/sec) on B(2), with an intraclass correlation coefficient of 0.91 (P < .0001). Bland-Altman plot showed good agreement, with a mean difference in measurement pairs of 0.017 mm(2)/sec +/- 0.096. The slope from the linear regression model was 0.89 (95% confidence interval: 0.63, 1.15) and the intercept was 0.01 (95% confidence interval: -0.08, 0.09). The CDC enables a quantitative description of contrast enhancement heterogeneity in lesions. Given the high reproducibility of the CDC metric, CDC appears promising for further qualification as an imaging biomarker of change measurement in response assessment. http://radiology.rsnajnls.org/cgi/content/full/248/3/901/DC1. RSNA, 2008

  12. 99m Tc-tazobactam, a novel infection imaging agent: Radiosynthesis, quality control, biodistribution, and infection imaging studies.

    Science.gov (United States)

    Rasheed, Rashid; Naqvi, Syed Ali Raza; Gillani, Syed Jawad Hussain; Zahoor, Ameer Fawad; Jielani, Asif; Saeed, Nidda

    2017-05-15

    The radiolabeled drug 99m Tc-tazobactam ( 99m Tc-TZB) was developed and assessed as an infection imaging agent in Pseudomonas aeruginosa and Salmonella enterica infection-induced animal models by comparing with inflammation induced animal models. Radiosynthesis of 99m Tc-TZB was assessed while changing ligand concentration, reducing agent concentration, pH, and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography. The analysis of the 99m Tc-TZB complex indicated >95% labeling yield and electrophoresis revealed complex is neutral in nature. The biodistribution study also showed predominantly renal excretion; however liver, stomach, and intestine also showed slight tracer agent uptake. The agent significantly accumulated in Pseudomonas aeruginosa and Salmonella enterica infection induced tissues 3.58 ± 0.26% and 2.43 ± 0.42% respectively at 1 hour postinjection. The inflamed tissue failed to uptake noticeable activity at 1 hour time point. The scintigraphic study results were found in accordance with biodistribution pattern. On the basis of our preliminary results, the newly developed 99m Tc-TZB can be used to diagnose bacterial infection and to discriminate between infected and inflamed tissues. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Development of 99mTc agents for imaging central neural system receptors

    International Nuclear Information System (INIS)

    2004-01-01

    Radiopharmaceuticals that bind to central neural system (CNS) receptors in vivo are potentially useful for understanding the pathophysiology of anumber of neurological and psychiatric disorders, their diagnosis and treatment. Carbon-11 labelled compounds and positron emission tomography(PET) imaging have played a vital role in establishing the usefulness of imaging the dopaminergic, cholinergic, serotonergic and benzodiazapine receptors, and relating the receptor density to disease status. Since the use of 11C agents is constrained due to their 20 min half-life, various radiohalogenated analogues based on the structure of 11C compounds have been successfully developed, providing comparable information. Iodine- 123 is the most widely employed of these radioisotopes; it has a longer, 13 h, half-life. Through the use of 123I, there has been a steady growth in CNS receptor imaging studies employing single photon emission computerized tomography (SPECT). SPECT, as compared with PET, has slightly inferior image resolution but has the advantage of being readily available worldwide. However, the 123I radiopharmaceutical is expensive and the distribution system outside of the major markets is not well developed for its supply on a routine basis. The ideal radioisotope for SPECT imaging is 99mTc, due to its low cost per dose, availability through commercially available generator systems and physical decay characteristics. Over 80% of all diagnostic nuclear medicine imaging studies worldwide are conducted using this radioisotope. Development of 99mTc radiopharmaceuticals for imaging CNS receptors is therefore of considerable importance. On the basis of the recommendations of a consultants meeting, the International Atomic Energy Agency (IAEA) initiated in 1996 a Co-ordinated Research Project (CRP) on Development of Agents for Imaging CNS Receptors based on 99mTc. At that time there were no 99mTc CNS receptor imaging radiopharmaceuticals available even though work on

  14. In vivo 3D PIXE-micron-CT imaging of Drosophila melanogaster using a contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Shigeo; Hamada, Naoki; Ishii, Keizo; Nozawa, Yuichiro; Ohkura, Satoru; Terakawa, Atsuki; Hatori, Yoshinobu; Fujiki, Kota; Fujiwara, Mitsuhiro; Toyama, Sho

    2015-04-01

    In this study, we developed a three-dimensional (3D) computed tomography (CT) in vivo imaging system for imaging small insects with micrometer resolution. The 3D CT imaging system, referred to as 3D PIXE-micron-CT (PIXEμCT), uses characteristic X-rays produced by ion microbeam bombardment of a metal target. PIXEμCT was used to observe the body organs and internal structure of a living Drosophila melanogaster. Although the organs of the thorax were clearly imaged, the digestive organs in the abdominal cavity could not be clearly discerned initially, with the exception of the rectum and the Malpighian tubule. To enhance the abdominal images, a barium sulfate powder radiocontrast agent was added. For the first time, 3D images of the ventriculus of a living D. melanogaster were obtained. Our results showed that PIXEμCT can provide in vivo 3D-CT images that reflect correctly the structure of individual living organs, which is expected to be very useful in biological research.

  15. The benefits of paired-agent imaging in molecular-guided surgery: an update on methods and applications (Conference Presentation)

    Science.gov (United States)

    Tichauer, Kenneth M.

    2016-03-01

    One of the major complications with conventional imaging-agent-based molecular imaging, particularly for cancer imaging, is variability in agent delivery and nonspecific retention in biological tissue. Such factors can account to "swamp" the signal arising from specifically bound imaging agent, which is presumably indicative of the concentration of targeted biomolecule. In the 1950s, Pressman et al. proposed a method of accounting for these delivery and retention effects by normalizing targeted antibody retention to the retention of a co-administered "untargeted"/control imaging agent [1]. Our group resurrected the approach within the last 5 years, finding ways to utilize this so-called "paired-agent" imaging approach to directly quantify biomolecule concentration in tissue (in vitro, ex vivo, and in vivo) [2]. These novel paired-agent imaging approaches capable of quantifying biomolecule concentration provide enormous potential for being adapted to and optimizing molecular-guided surgery, which has a principle goal of identifying distinct biological tissues (tumor, nerves, etc…) based on their distinct molecular environment. This presentation will cover the principles and nuances of paired-agent imaging, as well as the current status of the field and future applications. [1] D. Pressman, E. D. Day, and M. Blau, "The use of paired labeling in the determination of tumor-localizing antibodies," Cancer Res, 17(9), 845-50 (1957). [2] K. M. Tichauer, Y. Wang, B. W. Pogue et al., "Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging," Phys Med Biol, 60(14), R239-69 (2015).

  16. Paired-agent fluorescent imaging to detect micrometastases in breast sentinel lymph node biopsy: experiment design and protocol development

    Science.gov (United States)

    Li, Chengyue; Xu, Xiaochun; Basheer, Yusairah; He, Yusheng; Sattar, Husain A.; Brankov, Jovan G.; Tichauer, Kenneth M.

    2018-02-01

    Sentinel lymph node status is a critical prognostic factor in breast cancer treatment and is essential to guide future adjuvant treatment. The estimation that 20-60% of micrometastases are missed by conventional pathology has created a demand for the development of more accurate approaches. Here, a paired-agent imaging approach is presented that employs a control imaging agent to allow rapid, quantitative mapping of microscopic populations of tumor cells in lymph nodes to guide pathology sectioning. To test the feasibility of this approach to identify micrometastases, healthy pig lymph nodes were stained with targeted and control imaging agent solution to evaluate the potential for the agents to diffuse into and out of intact nodes. Aby-029, an anti-EGFR affibody was labeled with IRDye 800CW (LICOR) as targeted agent and IRDye 700DX was hydrolyzed as a control agent. Lymph nodes were stained and rinsed by directly injecting the agents into the lymph nodes after immobilization in agarose gel. Subsequently, lymph nodes were frozen-sectioned and imaged under an 80-um resolution fluorescence imaging system (Pearl, LICOR) to confirm equivalence of spatial distribution of both agents in the entire node. The binding potentials were acquired by a pixel-by-pixel calculation and was found to be 0.02 +/- 0.06 along the lymph node in the absence of binding. The results demonstrate this approach's potential to enhance the sensitivity of lymph node pathology by detecting fewer than 1000 cell in a whole human lymph node.

  17. Hypoxic Episodes in Bronchopulmonary Dysplasia.

    Science.gov (United States)

    Martin, Richard J; Di Fiore, Juliann M; Walsh, Michele C

    2015-12-01

    Hypoxic episodes are troublesome components of bronchopulmonary dysplasia (BPD) in preterm infants. Immature respiratory control seems to be the major contributor, superimposed on abnormal respiratory function. Relatively short respiratory pauses may precipitate desaturation and bradycardia. This population is predisposed to pulmonary hypertension; it is likely that pulmonary vasoconstriction also plays a role. The natural history has been well-characterized in the preterm population at risk for BPD; however, the consequences are less clear. Proposed associations of intermittent hypoxia include retinopathy of prematurity, sleep disordered breathing, and neurodevelopmental delay. Future study should address whether these associations are causal relationships. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Synthesis, biological evaluation, and baboon PET imaging of the potential adrenal imaging agent cholesteryl-p-[18f]fluorobenzoate

    International Nuclear Information System (INIS)

    Jonson, Stephanie D.; Welch, Michael J.

    1999-01-01

    Cholesteryl-p-[ 18 F]fluorobenzoate ([ 18 F]CFB) was investigated as a potential adrenal positron emission tomography (PET) imaging agent for the diagnostic imaging of adrenal disorders. We describe the synthesis, biodistribution, adrenal autoradiography, and baboon PET imaging of [ 18 F]CFB. The synthesis of [ 18 F]CFB was facilitated by the use of a specially designed microwave cavity that was instrumental in effecting 70-83% incorporation of fluorine-18 in 60 s via [ 18 F]fluoro-for-nitro exchange. Tissue distribution studies in mature female Sprague-Dawley rats showed good accumulation of [ 18 F]CFB in the steroid-secreting tissues, adrenals and ovaries, at 1 h postinjection. The effectiveness of [ 18 F]CFB to accumulate in diseased adrenals was shown through biodistribution studies in hypolipidemic rats, which showed a greater than threefold increase in adrenal uptake at 1 h and increased adrenal/liver and adrenal/kidney ratios. Analysis of the metabolites at 1 h in the blood, adrenals, spleen, and ovaries of hypolipidemic and control rats showed the intact tracer representing greater than 86%, 93%, 92%, and 82% of the accumulated activity, respectively. [ 18 F]CFB was confirmed to selectively accumulate in the adrenal cortex versus the adrenal medulla by autoradiography. Normal baboon PET imaging with [ 18 F]CFB effectively showed adrenal localization as early as 15 min after injection of the tracer, with enhanced adrenal contrast seen at 60-70 min. These results suggest that [ 18 F]CFB may be useful as an adrenal PET imaging agent for assessing adrenal disorders

  19. Barium sulfate suspension as a negative oral contrast agent for MR imaging

    International Nuclear Information System (INIS)

    Li, K.C.P.; Tart, R.P.; Fitzsimmons, J.R.; Storm, B.; Mao, J.

    1989-01-01

    Proton spectroscopy with linewidth measurements and MR imaging were performed on various commercially available barium sulfate suspensions as well as inorganic sulfates and barium salts. Approximately 500 mL of 20%, 40%, 60%, and 70% wt/wt single-contrast oral barium sulfate suspensions were administered to four normal volunteers, and MR imaging was performed with both a 1.5-T and a 0.15-T MR imager. As much as 80% of the small bowel and the entire colon were well visualized with the 60% or 70% wt/wt single-contrast barium sulfate suspensions. The authors conclude that barium sulfate suspensions are useful as oral MR contrast agents

  20. Residualization Rates of Near Infrared Dyes for the Rational Design of Molecular Imaging Agents

    Science.gov (United States)

    Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M.

    2016-01-01

    Purpose Near infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. Procedures In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, BODIPY, and oxazine/thiazine/carbopyronin). Results We identify residualizing (half-life > 24 hrs) and non-residualizing dyes (half-life < 24 hrs) in both the far red (~650-680 nm) and near infrared (~740-800 nm) regions. Conclusions This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design. PMID:25869081

  1. The preparation and identification of peptide imaging agent of lung cancer

    International Nuclear Information System (INIS)

    Chu Liping; Wang Yan; Wang Yueying; Liu Jinjian; Wu Hongying; Liu Jianfeng

    2010-01-01

    Objective: To screen in vivo lung cancer specific binding 7-peptide from T7 phage display random peptide library and prepare peptide imaging agent in early in early diagnosis of lung cancer. Methods: Used phage display in vivo technology to get the 7-peptide phage that can bind the lung cancer specifically, then sequenced and synthesized 7-peptide. After being labeled by 125 I, this 7-peptide was injected into mice via vein and the distribution in the mice tumor mold was observed. Results: One 7-peptide was obtained after four rounds of screening, and the peptide could bind lung cancer tissue specifically. Metabolism of this peptide in mice was fast and imaging of lung cancer was best two hours later after injection. The distribution in vivo decreased and almost disappeared after six hours. Conclusion: This 7-peptide could be used to image and diagnose of lung cancer effectively. (authors)

  2. Development of I-123 labeled angiostatin as a novel cancer imaging agent

    International Nuclear Information System (INIS)

    Lee, Kyung Han; Lee, Sang Yoon; Choe, Yearn Seong; Paik, Jin Young; Kim, Sun A; Han, Yu Mi; Kim, Byung Tae

    2000-01-01

    Since angiostatin is a promising anticancer agent that target tumor endothelial cells, it may have advantages over many current tumor imaging agents by overcoming problems such as poor delivery or multi-drug resistance. We therefore synthesized radiolabeled agniostatin and tested it in vivo. 123 -angiostatin was synthesized using the Bolton Hunter method. 123 I labeled plasminogen lysin-binding-site (LBS) was also synthesized. Blood clearance of he radiotracer was measured in SD rats, while tissue distribution was assessed in ICR mice at 1,4, and 18 hr. Pinhole scintigraphy was performed in SD rats and in nude mice bearing RR 1022 tumors at various time points. Radiochemical yield of 123 I-angiostatin approximated 20%. In vivo distribution demonstrated stability of the label for at least 20 hr. 123 I-angiostatin was cleared from the circulation in a biexponential manner with rapid early clearance followed by a slower rate of elimination Tissue distribution in mice showed the highest uptake in the kidneys which was the major route of excretion. This was followed by the lung, liver, and myocardium whose uptake of 1.5∼2% ID/gm at 1 hrs gradually decreased over time (all p 123 I-angiostatin and 123 I-LBS images in SD rates showed a similar distribution. Blood pool activity gradually cleared while tumor uptake increased over time, resulting in a high tumor to non tumor ratio at 20 hr. 123 I-angiostatin has promising potential as a new tumor imaging agent. Further study is warranted to assess its mechanism of uptake and precise role in cancer imaging

  3. Magnetic resonance imaging of osteosarcoma using a bis(alendronate)-based bone-targeted contrast agent.

    Science.gov (United States)

    Ge, Pingju; Sheng, Fugeng; Jin, Yiguang; Tong, Li; Du, Lina; Zhang, Lei; Tian, Ning; Li, Gongjie

    2016-12-01

    Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd 2 -diethylenetriaminepentaacetate-bis(alendronate) (Gd 2 -DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pK a , complex constant, and T 1 relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd 2 -DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd 2 -DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r 1 ) of 7.613mM -1 s -1 (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd 2 -DTPA-BA was much higher than that of Gd-DTPA after intravenous injection to the mice. More importantly, the MR imaging of osteosarcoma was significantly improved by Gd 2 -DTPA-BA. The signal intensity of Gd 2 -DTPA-BA reached 120.3% at 50min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd 2 -DTPA-BA in the osteosarcoma-bearing mice was very high to 130 at 180min. Furthermore, the contrast enhancement could also be found in the lung due to metastasis of osteosarcoma. Gd 2 -DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer's disease mouse models.

    Directory of Open Access Journals (Sweden)

    Scott B Raymond

    Full Text Available Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5+/-5.4-fold increase in Trypan blue fluorescence and 2.7+/-1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP, across a large age range (9-26 months, with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases.

  5. Ferric ammonium citrate as a positive bowel contrast agent for MR imaging of the upper abdomen

    Energy Technology Data Exchange (ETDEWEB)

    Kivelitz, D.; Taupitz, M.; Hamm, B. [Universitaetsklinikum Charite, Berlin (Germany). Inst. fuer Radiologie; Gehl, H.B. [Medizinische Univ. Luebeck (Germany). Inst. fuer Radiologie; Heuck, A. [Muenchen Univ. (Germany). Radiologische Klinik; Krahe, T. [Koeln Univ. (Germany). Inst. fuer Radiologische Diagnostik; Lodemann, K.P. [Bracco-Byk Gulden GmbH, Konstanz (Germany)

    1999-07-01

    Purpose: To evaluate the safety and diagnostic efficacy of two different doses of ferric ammonium citrate as a paramagnetic oral contrast agent for MR imaging of the upper abdomen. Material and methods: Ninety-nine adult patients referred for MR imaging for a known or suspected upper abdominal pathology were included in this randomized multicenter double-blind clinical trial. Imaging was performed with spin-echo (T1- and T2-weighted) and gradient-echo (T1-weighted) techniques before and after administration of either 1200 mg or 2400 mg of ferric ammonium citrate dissolved in 600 ml of water. Safety analysis included monitoring of vital signs, assessment of adverse events, and laboratory testing. Efficacy with regard to organ distension, contrast distribution, bowel enhancement and delineation of adjacent structures was graded qualitatively. Results: No serious adverse events were reported for either of the two concentrations. A total of 31 minor side effects were noted, of which significantly more occurred in the higher dose group (p<0.01). The diagnostic confidence in defining or excluding disease was graded as better after contrast administration for 48% of all images. Marked or moderate enhancement of the upper gastrointestinal tract was achieved at both doses in 69.5% of cases with no evident difference between the two doses. The higher dose tended to show better results in terms of the contrast assessment parameters. Conclusion: Ferric ammonium citrate is a safe and effective oral contrast agent for MR imaging of the upper abdomen at two different dose levels. The higher dose showed a tendency toward better imaging results while the lower dose caused significantly fewer side effects. Therefore, the 1200 mg dose can be recommended in view of the risk-to-benefit ratio. (orig.)

  6. Thermal dependence of ultrasound contrast agents scattering efficiency for echographic imaging techniques

    Science.gov (United States)

    Biagioni, Angelo; Bettucci, Andrea; Passeri, Daniele; Alippi, Adriano

    2015-06-01

    Ultrasound contrast agents are used in echographic imaging techniques to enhance image contrast. In addition, they may represent an interesting solution to the problem of non-invasive temperature monitoring inside the human body, based on some thermal variations of their physical properties. Contrast agents, indeed, are inserted into blood circulation and they reach the most important organs inside the human body; consequently, any thermometric property that they may possess, could be exploited for realizing a non-invasive thermometer. They essentially are a suspension of microbubbles containing a gas enclosed in a phospholipid membrane; temperature variations induce structural modifications of the microbubble phospholipid shell, thus causing thermal dependence of contrast agent's elastic characteristics. In this paper, the acoustic scattering efficiency of a bulk suspension of of SonoVue® (Bracco SpA Milan, Italy) has been studied using a pulse-echo technique in the frequency range 1-17 MHz, as it depends upon temperatures between 25 and 65°C. Experimental data confirm that the ultrasonic attenuation coefficient of SonoVue® depends on temperature between 25 and 60°C. Chemical composition of the bubble shell seem to support the hypothesis that a phase transition in the microstructure of lipid-coated microbubbles could play a key role in explaining such effect.

  7. ESGAR consensus statement on liver MR imaging and clinical use of liver-specific contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Neri, E.; Boraschi, P.; Bartolozzi, C. [University of Pisa, Department of Diagnostic and Interventional Radiology, Pisa (Italy); Bali, M.A.; Matos, C. [Hopital Erasme, MRI Clinics, Department of Radiology, Bruxelles (Belgium); Ba-Ssalamah, A. [The General Hospital of the Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Brancatelli, G. [University of Palermo, Department of Radiology, Palermo (Italy); Alves, F.C. [University Hospital of Coimbra, Medical Imaging Department and Faculty of Medicine, Coimbra (Portugal); Grazioli, L. [Spedali Civili di Brescia, Department of Radiology, Brescia (Italy); Helmberger, T. [Academic Teaching Hospital of the Technical University, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Klinikum Bogenhausen, Munich (Germany); Lee, J.M. [Seoul National University College of Medicine, Division of Abdominal Imaging, Department of Radiology, Seoul (Korea, Republic of); Manfredi, R. [University of Verona, Department of Radiology, Verona (Italy); Marti-Bonmati, L. [Hospital Universitario y Politecnico La Fe, Area Clinica de Imagen Medica, Valencia (Spain); Merkle, E.M. [Universitaetsspital Basel, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland); Op De Beeck, B. [Antwerp University Hospital, Department of Radiology, Edegem (Belgium); Schima, W. [KH Goettlicher Heiland, Krankenhaus der Barmherzigen Schwestern and Sankt Josef-Krankenhaus, Department of Diagnostic and Interventional Radiology, Vienna (Austria); Skehan, S. [St Vincent' s University Hospital, Department of Radiology, Dublin (Ireland); Vilgrain, V. [Assistance Publique-Hopitaux de Paris, APHP, Hopital Beaujon, Radiology Department, Clichy, Paris (France); Zech, C. [Universitaetsspital Basel, Abteilungsleiter Interventionelle Radiologie, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland)

    2016-04-15

    To develop a consensus and provide updated recommendations on liver MR imaging and the clinical use of liver-specific contrast agents. The European Society of Gastrointestinal and Abdominal Radiology (ESGAR) formed a multinational European panel of experts, selected on the basis of a literature review and their leadership in the field of liver MR imaging. A modified Delphi process was adopted to draft a list of statements. Descriptive and Cronbach's statistics were used to rate levels of agreement and internal reliability of the consensus. Three Delphi rounds were conducted and 76 statements composed on MR technique (n = 17), clinical application of liver-specific contrast agents in benign, focal liver lesions (n = 7), malignant liver lesions in non-cirrhotic (n = 9) and in cirrhotic patients (n = 18), diffuse and vascular liver diseases (n = 12), and bile ducts (n = 13). The overall mean score of agreement was 4.84 (SD ±0.17). Full consensus was reached in 22 % of all statements in all working groups, with no full consensus reached on diffuse and vascular diseases. The consensus provided updated recommendations on the methodology, and clinical indications, of MRI with liver specific contrast agents in the study of liver diseases. (orig.)

  8. Labelling and biodistribution of /sup 99m/Tc-ceftriaxone: a new imaging agent

    International Nuclear Information System (INIS)

    Khurshid, Z.; Roohi, S.; Zahoor, R.; Tariq, S.

    2012-01-01

    Most commonly used infection imaging agents are specific for inflammation. Some newer agents like labeled antimicrobials and peptides have shown infection seeking properties. Research is underway for synthesis of newer imaging agents specific for infections. In this quest we have labeled and bio evaluated /sup 99m/Tc-ceftriaxone. Ceftriaxone is a commonly used third generation cephalosporin antibiotic having a broad anti-bacterial spectrum but has more specificity for gram-negative bacteria. /sup 99m/Tc-ceftriaxone was prepared at ph 7 by adding 30 mg of ligand to /sup 99m/Tc in the presence of 50 mu g of SnCl/sub 2/./sup 2/H/sub 2/O. Boiling for ten minutes gave maximum labeling yield (96+1.76%). The stability at room temperature both with and without human serum was more than 90% till 24 hours. In-vitro binding revealed maximum binding of 68% and 47% with E.coli and S.aureus respectively after 4 hours incubation. Biodistribution studies in normal rats showed maximum uptake in hepatobiliary system followed by kidney. In infection and inflammation models the maximum target to non- target ratios of 12.66 +- 2.59, 2.36 +- 0.30 and 1.44 +- 0.53 were achieved with E. coli, S. aureus and oil inflammation respectively 4 hours post injection. Scintigraphic findings also correlated with biodistribution results. (Orig./A.B.)

  9. An agent harms a victim: A functional magnetic resonance imaging study on specific moral emotions

    International Nuclear Information System (INIS)

    Kedia, G.; Kedia, G.; Martinot, J.L.; Kedia, G.; Martinot, J.L.; Kedia, G.; Hilton, D.; Berthoz, S.; Wessa, M.

    2008-01-01

    The statement 'An agent harms a victim' depicts a situation that triggers moral emotions. Depending on whether the agent and the victim are the self or someone else, it can lead to four different moral emotions: self-anger ('I harm myself'), guilt ('I harm someone'), other-anger ('someone harms me'), and compassion ('someone harms someone'). In order to investigate the neural correlates of these emotions, we examined brain activation patterns elicited by variations in the agent (self vs. other) and the victim (self vs. other) of a harmful action. Twenty-nine healthy participants underwent functional magnetic resonance imaging while imagining being in situations in which they or someone else harmed themselves or someone else. Results indicated that the three emotional conditions associated with the involvement of other, either as agent or victim (guilt, other-anger, and compassion conditions), all activated structures that have been previously associated with the Theory of Mind (ToM, the attribution of mental states to others), namely, the dorsal medial prefrontal cortex, the precuneus, and the bilateral temporo-parietal junction. Moreover, the two conditions in which both the self and other were concerned by the harmful action (guilt and other-anger conditions) recruited emotional structures (i. e., the bilateral amygdala, anterior cingulate, and basal ganglia). These results suggest that specific moral emotions induce different neural activity depending on the extent to which they involve the self and other. (authors)

  10. Development of 99Tcm-Q3 as a new type myocardial perfusion imaging agent

    International Nuclear Information System (INIS)

    Li Yunchun; Tan Tianzhi; Fan Chengzhong; Zhao Keqing; Wei Xihe; Li Quan

    1999-01-01

    Objective: To develop 99 Tc m -N,N'-ethylene-bis (acetylacetone iminato) bis [tris (3-methoxy-1-propyl) phosphine] ( 99 Tc m -Q 3 ) as a new type of myocardial perfusion imaging agent. Methods: After N,N'-ethylene-bis (acetylacetone iminato) and tris (3-methoxy-1-propyl) phosphine were made, N,N'-ethylene-bis (acetylacetone iminato) was labelled using reduced 99 Tc m O 4 - by SnCl 2 ·2H 2 O under the presence of alkali, then tris (3-methoxy-1-propyl) phosphine was added and reacted for ten minutes, 99 Tc m -Q 3 was obtained at the end. Biodistribution in mice, in vitro stability and acute toxicity of 99 Tc m -Q 3 were examined. Results: 99 Tc m -Q 3 was taken up rapidly by the heart, and the uptake rate was very high, by 5 minutes post injection, 24.66% of the injected dose was taken up in per gram heart, and no significant washout was shown up by 4 hours. But 99 Tc m -Q 3 was cleaned out rapidly from blood, lung and liver. No poisonousness and adverse effects were observed, and its stability lasted more than 6 hours. Conclusions: 99 Tc m -Q 3 is a fairly good myocardial perfusion imaging agent for improving the quality of myocardial perfusion imaging

  11. Magnetic resonance imaging using paramagnetic contrast agents in the clinical evaluation of myocardial infarction. Chapter 15

    International Nuclear Information System (INIS)

    Dijkman, P.R.M. van; Wall, E.E. van der

    1992-01-01

    MRI is noninvasive and specific method for production of high resolution tomographic images in blocks of 3D information. Apart from scintigraphic techniques and computed tomography for evaluation of myocardial ischemia and infarcts, MRI has emerged as a new diagnostic technique to study the extent of anatomical and functional abnormalities in patients with coronary artery disease. Conventional noncontrast MRI can identify acute-infarcted myocardial areas, although the difficulty in identifying myocardial ischemia and infarct with noncontrast MRI suggests a potential role for contrast enhanced MRI. Use of the paramagnetic contrast agent gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) improves depiction of infarcted myocardium on T1-weighted spin -echo MR images that are obtained soon after acute myocardial infarction. This is of particular interest for the estimation of myocardial infarct size. Furthermore, ultrafast subsecond imaging, in combination with Gd-DTPA, offers the potential to analyze cardiac first pass and myocardial perfusion. The development of nontoxic paramagnetic contrast agents which are selectively taken up by viable myocardium would be helpful in assessing the presence of ischemic/infarcted myocardium salvage by MRI following reperfusion. (author). 58 refs., 6 figs

  12. Lanthanide Phytanates: Liquid-Crystalline Phase Behavior, Colloidal Particle Dispersions, and Potential as Medical Imaging Agents

    Energy Technology Data Exchange (ETDEWEB)

    Conn, Charlotte E.; Panchagnula, Venkateswarlu; Weerawardena, Asoka; Waddington, Lynne J.; Kennedy, Danielle F.; Drummond, Calum J. (CSIRO/MHT); (CSIRO/MSE)

    2010-08-23

    Lanthanide salts of phytanic acid, an isoprenoid-type amphiphile, have been synthesized and characterized. Elemental analysis and FTIR spectroscopy were used to confirm the formed product and showed that three phytanate anions are complexed with one lanthanide cation. The physicochemical properties of the lanthanide phytanates were investigated using DSC, XRD, SAXS, and cross-polarized optical microscopy. Several of the hydrated salts form a liquid-crystalline hexagonal columnar mesophase at room temperature, and samarium(III) phytanate forms this phase even in the absence of water. Select lanthanide phytanates were dispersed in water, and cryo-TEM images indicate that some structure has been retained in the dispersed phase. NMR relaxivity measurements were conducted on these systems. It has been shown that a particulate dispersion of gadolinium(III) phytanate displays proton relaxivity values comparable to those of a commercial contrast agent for magnetic resonance imaging and a colloidal dispersion of europium(III) phytanate exhibits the characteristics of a fluorescence imaging agent.

  13. Lanthanide Phytanates: Liquid-Crystalline Phase Behavior, Colloidal Particle Dispersions, and Potential as Medical Imaging Agents

    International Nuclear Information System (INIS)

    Conn, Charlotte E.; Panchagnula, Venkateswarlu; Weerawardena, Asoka; Waddington, Lynne J.; Kennedy, Danielle F.; Drummond, Calum J.

    2010-01-01

    Lanthanide salts of phytanic acid, an isoprenoid-type amphiphile, have been synthesized and characterized. Elemental analysis and FTIR spectroscopy were used to confirm the formed product and showed that three phytanate anions are complexed with one lanthanide cation. The physicochemical properties of the lanthanide phytanates were investigated using DSC, XRD, SAXS, and cross-polarized optical microscopy. Several of the hydrated salts form a liquid-crystalline hexagonal columnar mesophase at room temperature, and samarium(III) phytanate forms this phase even in the absence of water. Select lanthanide phytanates were dispersed in water, and cryo-TEM images indicate that some structure has been retained in the dispersed phase. NMR relaxivity measurements were conducted on these systems. It has been shown that a particulate dispersion of gadolinium(III) phytanate displays proton relaxivity values comparable to those of a commercial contrast agent for magnetic resonance imaging and a colloidal dispersion of europium(III) phytanate exhibits the characteristics of a fluorescence imaging agent.

  14. Performance characteristics of magnetic resonance imaging without contrast agents or sedation in pediatric appendicitis

    Energy Technology Data Exchange (ETDEWEB)

    Didier, Ryne A.; Hopkins, Katharine L.; Coakley, Fergus V.; Foster, Bryan R. [Oregon Health and Science University, Department of Diagnostic Radiology, Portland, OR (United States); Krishnaswami, Sanjay [Oregon Health and Science University, Department of Surgery, Portland, OR (United States); Oregon Health and Science University, Department of Pediatrics, Portland, OR (United States); Spiro, David M. [Oregon Health and Science University, Department of Pediatrics, Portland, OR (United States)

    2017-09-15

    Magnetic resonance imaging (MRI) has emerged as a promising modality for evaluating pediatric appendicitis. However optimal imaging protocols, including roles of contrast agents and sedation, have not been established and diagnostic criteria have not been fully evaluated. To investigate performance characteristics of rapid MRI without contrast agents or sedation in the diagnosis of pediatric appendicitis. We included patients ages 4-18 years with suspicion of appendicitis who underwent rapid MRI between October 2013 and March 2015 without contrast agent or sedation. After two-radiologist review, we determined performance characteristics of individual diagnostic criteria and aggregate diagnostic criteria by comparing MRI results to clinical outcomes. We used receiver operating characteristic (ROC) curves to determine cut-points for appendiceal diameter and wall thickness for optimization of predictive power, and we calculated area under the curve (AUC) as a measure of test accuracy. Ninety-eight MRI examinations were performed in 97 subjects. Overall, MRI had a 94% sensitivity, 95% specificity, 91% positive predictive value and 97% negative predictive value. Optimal cut-points for appendiceal diameter and wall thickness were ≥7 mm and ≥2 mm, respectively. Independently, those cut-points produced sensitivities of 91% and 84% and specificities of 84% and 43%. Presence of intraluminal fluid (30/33) or localized periappendiceal fluid (32/33) showed a significant association with acute appendicitis (P<0.01), with sensitivities of 91% and 97% and specificities of 60% and 50%. For examinations in which the appendix was not identified by one or both reviewers (23/98), the clinical outcome was negative. Rapid MRI without contrast agents or sedation is accurate for diagnosis of pediatric appendicitis when multiple diagnostic criteria are considered in aggregate. Individual diagnostic criteria including optimized cut-points of ≥7 mm for diameter and ≥2 mm for wall

  15. Performance characteristics of magnetic resonance imaging without contrast agents or sedation in pediatric appendicitis

    International Nuclear Information System (INIS)

    Didier, Ryne A.; Hopkins, Katharine L.; Coakley, Fergus V.; Foster, Bryan R.; Krishnaswami, Sanjay; Spiro, David M.

    2017-01-01

    Magnetic resonance imaging (MRI) has emerged as a promising modality for evaluating pediatric appendicitis. However optimal imaging protocols, including roles of contrast agents and sedation, have not been established and diagnostic criteria have not been fully evaluated. To investigate performance characteristics of rapid MRI without contrast agents or sedation in the diagnosis of pediatric appendicitis. We included patients ages 4-18 years with suspicion of appendicitis who underwent rapid MRI between October 2013 and March 2015 without contrast agent or sedation. After two-radiologist review, we determined performance characteristics of individual diagnostic criteria and aggregate diagnostic criteria by comparing MRI results to clinical outcomes. We used receiver operating characteristic (ROC) curves to determine cut-points for appendiceal diameter and wall thickness for optimization of predictive power, and we calculated area under the curve (AUC) as a measure of test accuracy. Ninety-eight MRI examinations were performed in 97 subjects. Overall, MRI had a 94% sensitivity, 95% specificity, 91% positive predictive value and 97% negative predictive value. Optimal cut-points for appendiceal diameter and wall thickness were ≥7 mm and ≥2 mm, respectively. Independently, those cut-points produced sensitivities of 91% and 84% and specificities of 84% and 43%. Presence of intraluminal fluid (30/33) or localized periappendiceal fluid (32/33) showed a significant association with acute appendicitis (P<0.01), with sensitivities of 91% and 97% and specificities of 60% and 50%. For examinations in which the appendix was not identified by one or both reviewers (23/98), the clinical outcome was negative. Rapid MRI without contrast agents or sedation is accurate for diagnosis of pediatric appendicitis when multiple diagnostic criteria are considered in aggregate. Individual diagnostic criteria including optimized cut-points of ≥7 mm for diameter and ≥2 mm for wall

  16. Chitosan-coated nickel-ferrite nanoparticles as contrast agents in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Ahmad, Tanveer; Bae, Hongsub; Iqbal, Yousaf; Rhee, Ilsu; Hong, Sungwook; Chang, Yongmin; Lee, Jaejun; Sohn, Derac

    2015-01-01

    We report evidence for the possible application of chitosan-coated nickel-ferrite (NiFe 2 O 4 ) nanoparticles as both T 1 and T 2 contrast agents in magnetic resonance imaging (MRI). The coating of nickel-ferrite nanoparticles with chitosan was performed simultaneously with the synthesis of the nickel-ferrite nanoparticles by a chemical co-precipitation method. The coated nanoparticles were cylindrical in shape with an average length of 17 nm and an average width of 4.4 nm. The bonding of chitosan onto the ferrite nanoparticles was confirmed by Fourier transform infrared spectroscopy. The T 1 and T 2 relaxivities were 0.858±0.04 and 1.71±0.03 mM −1 s −1 , respectively. In animal experimentation, both a 25% signal enhancement in the T 1 -weighted mage and a 71% signal loss in the T 2 -weighted image were observed. This demonstrated that chitosan-coated nickel-ferrite nanoparticles are suitable as both T 1 and T 2 contrast agents in MRI. We note that the applicability of our nanoparticles as both T 1 and T 2 contrast agents is due to their cylindrical shape, which gives rise to both inner and outer sphere processes of nanoparticles. - Highlights: • Chitosan-coated nickel-ferrite (Ni-Fe 2 O 4 ) nanoparticles were synthesized in an aqueous system by chemical co-precipitation. • The characterization of bare and chitosan-coated nanoparticles were performed using various analytical tools, such as TEM, FTIR, XRD, and VMS. • We evaluated the coated particles as potential T 1 and T 2 contrast agents for MRI by measuring T 1 and T 2 relaxation times as a function of iron concentration. • Both T 1 and T 2 effects were also observed in animal experimentation

  17. Development of a PET Prostate-Specific Membrane Antigen Imaging Agent: Preclinical Translation for Future Clinical Application

    Science.gov (United States)

    2017-10-01

    are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by...phase 0) application to the FDA by the end of the funding period. The small molecule imaging agents under study home to prostate specific membrane...funding period. The small molecule imaging agents under study home to prostate specific membrane antigen (PSMA) that is prevalent on a majority of

  18. Nerve-Highlighting Fluorescent Contrast Agents for Image-Guided Surgery

    Directory of Open Access Journals (Sweden)

    Summer L. Gibbs-Strauss

    2011-03-01

    Full Text Available Nerve damage is the major morbidity of many surgeries, resulting in chronic pain, loss of function, or both. The sparing of nerves during surgical procedures is a vexing problem because surrounding tissue often obscures them. To date, systemically administered nerve-highlighting contrast agents that can be used for nerve-sparing image-guided surgery have not been reported. In the current study, physicochemical and optical properties of 4,4‘-[(2-methoxy-1,4-phenylenedi-(1E-2,1-ethenediyl]bis-benzenamine (BMB and a newly synthesized, red-shifted derivative 4-[(1E-2-[4-[(1E-2-[4-aminophenyl]ethenyl]-3-methoxyphenyl]ethenyl]-benzonitrile (GE3082 were characterized in vitro and in vivo. Both agents crossed the blood-nerve barrier and blood-brain barrier and rendered myelinated nerves fluorescent after a single systemic injection. Although both BMB and GE3082 also exhibited significant uptake in white adipose tissue, GE3082 underwent a hypsochromic shift in adipose tissue that provided a means to eliminate the unwanted signal using hyperspectral deconvolution. Dose and kinetic studies were performed in mice to determine the optimal dose and drug-imaging interval. The results were confirmed in rat and pig, with the latter used to demonstrate, for the first time, simultaneous fluorescence imaging of blood vessels and nerves during surgery using the FLARE™ (Fluorescence-Assisted Resection and Exploration imaging system. These results lay the foundation for the development of ideal nerve-highlighting fluorophores for image-guided surgery.

  19. Cerebral circulation and prognosis of the patients with hypoxic encephalopathy

    International Nuclear Information System (INIS)

    Nogami, Kenichiro; Fujii, Masami; Kashiwagi, Shiro; Sadamitsu Daikai; Maekawa, Tsuyoshi

    2000-01-01

    Recent progress in cardiopulmonary resuscitation techniques improved the survival rate of patients with acute cardiopulmonary disturbances. However, severe cerebral complications remained frequently in patients who survived the acute stage. Early prediction of cerebral prognosis is important to optimize the management of these patients. We examined the relations between radiological findings (Xe-CT and MRI) and cerebral prognosis. Patients included in this study were selected from all patients with hypoxic encephalopathy admitted to our hospital. There were 11 men and 10 women. Causes of hypoxic encephalopathy were heart disease (11 cases), suffocation (4 cases), CO intoxication (2 cases), asthma (1 case), pneumothorax (1 case), anaphyraxy shock (1 case) and electric shock (1 case). Xe-CT and MRI were carried out 3 weeks after the onset. Cerebral blood flow (CBF) of the patients was measured at rest and 15 minutes after intravenous administration of acetazolamide (1 g). The prognosis was evaluated 3 months after the onset in accordance with Glasgow Outcome Scale (GOS). Low hemispheric CBF (30 ml/100 g/min), poor reactivity of acetazolamide challenge test (10 ml/100 g/min), presence of hyperintensity areas in the basal ganglia in T1 weighted images (T1WI) and T2 weighted images (T2WI) are the factors associated with poor outcome in hypoxic encephalopathy. (author)

  20. Chemistry of paramagnetic and diamagnetic contrast agents for Magnetic Resonance Imaging and Spectroscopy

    International Nuclear Information System (INIS)

    Perez-Mayoral, Elena; Negri, Viviana; Soler-Padros, Jordi; Cerdan, Sebastian; Ballesteros, Paloma

    2008-01-01

    We provide a brief overview of the chemistry and most relevant properties of paramagnetic and diamagnetic contrast agents (CAs) for Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging. Paramagnetic CAs for MRI consist mainly of Gd(III) complexes from linear or macrocyclic polyaminopolycarboxylates. These agents reduce, the relaxation times T 1 and T 2 of the water protons in a concentration dependent manner, increasing selectively MRI contrast in those regions in which they accumulate. In most instances they provide anatomical information on the localization of lesions and in some specific cases they may allow to estimate some physiological properties of tissues including mainly vascular performance. Because of its ability to discriminate easily between normal and diseased tissue, extracellular pH (pH e ) has been added recently, to the battery of variables amenable to MRI investigation. A variety of Gd(III) containing macrocycles sensitive to pH, endogenous or exogenous polypeptides or even liposomes have been investigated for this purpose, using the pH dependence of their relaxivity or magnetization transfer rate constant (chemical exchange saturation transfer, CEST). Many environmental circumstances in addition to pH affect, however, relaxivity or magnetization transfer rate constants of these agents, making the results of pH measurements by MRI difficult to interpret. To overcome these limitations, our laboratory synthesized and developed a novel series of diamagnetic CAs for Magnetic Resonance Spectroscopic Imaging, a new family of monomeric and dimeric imidazolic derivatives able to provide unambiguous measurements of pH e , independent of water relaxivity, diffusion or exchange

  1. Chemistry of paramagnetic and diamagnetic contrast agents for Magnetic Resonance Imaging and Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Mayoral, Elena [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Departamento de Quimica Inorganica y Quimica Tecnica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Negri, Viviana; Soler-Padros, Jordi [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Cerdan, Sebastian [Laboratorio de Imagen Espectroscopica por Resonancia Magnetica (LIERM), Instituto de Investigaciones Biomedicas ' Alberto Sols' , CSIC/UAM, c/Arturo Duperier 4, E-28029 Madrid (Spain); Ballesteros, Paloma [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain)], E-mail: pballesteros@ccia.uned.es

    2008-09-15

    We provide a brief overview of the chemistry and most relevant properties of paramagnetic and diamagnetic contrast agents (CAs) for Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging. Paramagnetic CAs for MRI consist mainly of Gd(III) complexes from linear or macrocyclic polyaminopolycarboxylates. These agents reduce, the relaxation times T{sub 1} and T{sub 2} of the water protons in a concentration dependent manner, increasing selectively MRI contrast in those regions in which they accumulate. In most instances they provide anatomical information on the localization of lesions and in some specific cases they may allow to estimate some physiological properties of tissues including mainly vascular performance. Because of its ability to discriminate easily between normal and diseased tissue, extracellular pH (pH{sub e}) has been added recently, to the battery of variables amenable to MRI investigation. A variety of Gd(III) containing macrocycles sensitive to pH, endogenous or exogenous polypeptides or even liposomes have been investigated for this purpose, using the pH dependence of their relaxivity or magnetization transfer rate constant (chemical exchange saturation transfer, CEST). Many environmental circumstances in addition to pH affect, however, relaxivity or magnetization transfer rate constants of these agents, making the results of pH measurements by MRI difficult to interpret. To overcome these limitations, our laboratory synthesized and developed a novel series of diamagnetic CAs for Magnetic Resonance Spectroscopic Imaging, a new family of monomeric and dimeric imidazolic derivatives able to provide unambiguous measurements of pH{sub e}, independent of water relaxivity, diffusion or exchange.

  2. Near-infrared light-responsive liposomal contrast agent for photoacoustic imaging and drug release applications.

    Science.gov (United States)

    Sivasubramanian, Kathyayini; Mathiyazhakan, Malathi; Wiraja, Christian; Upputuri, Paul Kumar; Xu, Chenjie; Pramanik, Manojit

    2017-04-01

    Photoacoustic imaging has become an emerging tool for theranostic applications. Not only does it help in release and therapeutic applications. We explore near-infrared light-sensitive liposomes coated with gold nanostars (AuNSs) for both imaging and drug release applications using a photoacoustic imaging system. Being amphiphilic, the liposomes lipid bilayer and the aqueous core enable encapsulation of both hydrophobic and hydrophilic drugs. The AuNSs on the surface of the liposomes act as photon absorbers due to their intrinsic surface plasmon resonance. Upon excitation by laser light at specific wavelength, AuNSs facilitate rapid release of the contents encapsulated in the liposomes due to local heating and pressure wave formation (photoacoustic wave). Herein, we describe the design and optimization of the AuNSs-coated liposomes and demonstrate the release of both hydrophobic and hydrophilic model drugs (paclitaxel and calcein, respectively) through laser excitation at near-infrared wavelength. The use of AuNSs-coated liposomes as contrast agents for photoacoustic imaging is also explored with tissue phantom experiments. In comparison to blood, the AuNSs-coated liposomes have better contrast (approximately two times) at 2-cm imaging depth.

  3. Magnetosomes used as biogenic MRI contrast agent for molecular imaging of glioblastoma model

    International Nuclear Information System (INIS)

    Boucher, Marianne

    2016-01-01

    This work takes place in the context of molecular imaging, which aims at tailoring medical treatments and therapies to the individual context by revealing molecular or cellular phenomenon of medical interest in the less invasive manner. In particular, it can be achieved with MRI molecular imaging using engineered iron-oxide contrast agent.This PhD thesis focuses on the study of a new class of iron-oxide contrast agent for high field MRI. Indeed, magnetosomes are natural iron-oxide vesicles produced by magneto-tactic bacteria. These bacteria synthesized such magnetic vesicles and ordered them like a nano-compass in order to facilitate their navigation in sediments. This explains why magnetosomes are awarded with tremendous magnetic properties: around 50 nm, mono-crystalline, single magnetic domain and high saturation magnetization. Furthermore, a wide variety of bacterial strains exist in nature and size and shape of magnetosomes are highly stable within strain and can be very different between strains. Finally, magnetosomes are naturally coated with a bi-lipidic membrane whose content is genetically determined. Lately, researchers have unravelled magnetosomes membrane protein contents, opening the way to create functionalized magnetosomes thanks to fusion of the gene coding for a protein of interest with the gene coding for an abundant protein at magnetosomes membrane.A new alternative path using living organisms to tackle the production of engineered high efficiency molecular imaging probes have been investigated with magneto-tactic bacteria in this PhD. The production and engineering of magnetosomes have been carried out by our partner, the Laboratoire de Bio-energetique Cellulaire (LBC, CEA Cadarache), and will be presented and discussed. We then characterized magnetosomes as contrast agent for high field MRI. We showed they present very promising contrasting properties in vitro, and assessed this observation in vivo by establishing they can be used as efficient

  4. Magnetic resonance imaging with liver-specific contrast agent in primary amyloidosis and intrahepatic cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, J.M.; Santoni-Rugiu, E.; Chabanova, E.; Logager, V.; Hansen, A.B.; Thomsen, H.S. [Depts. of Radiology and Pathology, Copenhagen Univ. Hospital, Herlev (Denmark)

    2007-02-15

    Magnetic resonance imaging (MRI) findings in hepatic amyloidosis are not well defined. Here, we report on a patient with renal failure caused by primary amyloidosis (AL type) who developed jaundice. Ultrasound and computed tomography were normal except for some ascites. MRI with oral manganese-containing contrast agent revealed several focal areas without contrast uptake in the hepatocytes and no bile secretion after 8 hours. No extrahepatic bile obstructions were found. Liver biopsy showed severe intraportal, vascular, and parenchymal amyloidosis causing severe cholestasis and atrophy of hepatocytes.

  5. Measurements of some basic constants of 68Ga(BAT-TECH) as an imaging agent

    International Nuclear Information System (INIS)

    Chen Huawei; Liu Boli

    1994-01-01

    The kinetic properties of a new myocardial imaging agent 68 Ga(BAT-TECH) are investigated and its thermodynamic constants are measured. The results are as follows: Citrate→BAT-TECH exchange reaction order is second-order; reaction rate k = 0.50 l/mol·s; activation energy E a = 56.6 kJ/mol; the stability constant of 68 Ga(BAT-TECH) lgβ = 14.9; the acid dissociation constants of BAT-TECH pK 1 = 4.62, pK 2 = 7.68, pK-3 = 8.68, pK 4 = 11.2

  6. Radiolabeled phosphonium salts as mitocondrial voltage sensors for positron emission tomography myocardial imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Yon; Min, Jung Joon [Dept. of Nuclear Medicine,Chonnam National University Medical School and Hwasun Hospital, Gwangju (Korea, Republic of)

    2016-09-15

    Despite substantial advances in the diagnosis of cardiovascular disease, {sup 18}F-labeled positron emission tomography (PET) radiopharmaceuticals remain necessary to diagnose heart disease because clinical use of current PET tracers is limited by their short half-life. Lipophilic cations such as phosphonium salts penetrate the mitochondrial membranes and accumulate in mitochondria of cardiomyocytes in response to negative inner-transmembrane potentials. Radiolabeled tetraphenyl phosphonium cation derivatives have been developed as myocardial imaging agents for PET. In this review, a general overview of these radiotracers, including their radiosynthesis, in vivo characterization, and evaluation is provided and clinical perspectives are discussed.

  7. evaluation of some technetium-99m fluoroquinolones complexes as imaging agents for bacterial inflammatory lesions

    International Nuclear Information System (INIS)

    Abdel-Kawy, O.A.A.

    2007-01-01

    in this study, the labeling method of ciprofloxacin and levofloxacin with technetium-99m and their biological evaluation in man-induced inflammation models were described . in -vitro microbiological evaluation of both complexes was also performed in order to investigate the effect of labeling on the activity and spectrum of both antibiotics. all the gathered biological data support the usefulness of 99m Tc-fluoroquinolones as infection imaging agents that could discriminate between infections and sterile inflammations. the freeze-dried form of levofloxacin kits was prepared and found to meet all the radiochemical and biological tests

  8. Imaging in Vivo Extracellular pH with a Single Paramagnetic Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agent

    Directory of Open Access Journals (Sweden)

    Guanshu Liu

    2012-01-01

    Full Text Available The measurement of extracellular pH (pHe has potential utility for cancer diagnoses and for assessing the therapeutic effects of pH-dependent therapies. A single magnetic resonance imaging (MRI contrast agent that is detected through paramagnetic chemical exchange saturation transfer (PARACEST was designed to measure tumor pHe throughout the range of physiologic pH and with magnetic resonance saturation powers that are not harmful to a mouse model of cancer. The chemical characterization and modeling of the contrast agent Yb3+-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, 10-o-aminoanilide (Yb-DO3A-oAA suggested that the aryl amine of the agent forms an intramolecular hydrogen bond with a proximal carboxylate ligand, which was essential for generating a practical chemical exchange saturation transfer (CEST effect from an amine. A ratio of CEST effects from the aryl amine and amide was linearly correlated with pH throughout the physiologic pH range. The pH calibration was used to produce a parametric pH map of a subcutaneous flank tumor on a mouse model of MCF-7 mammary carcinoma. Although refinements in the in vivo CEST MRI methodology may improve the accuracy of pHe measurements, this study demonstrated that the PARACEST contrast agent can be used to generate parametric pH maps of in vivo tumors with saturation power levels that are not harmful to a mouse model of cancer.

  9. Imaging Primary Mouse Sarcomas After Radiation Therapy Using Cathepsin-Activatable Fluorescent Imaging Agents

    Energy Technology Data Exchange (ETDEWEB)

    Cuneo, Kyle C. [Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Mito, Jeffrey K.; Javid, Melodi P. [Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina (United States); Ferrer, Jorge M. [Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts (United States); Kim, Yongbaek [Department of Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul (Korea, Republic of); Lee, W. David [The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts (United States); Bawendi, Moungi G. [Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts (United States); Brigman, Brian E. [Department of Orthopedic Surgery, Duke University School of Medicine, Durham, North Carolina (United States); Kirsch, David G., E-mail: david.kirsch@duke.edu [Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina (United States)

    2013-05-01

    Purpose: Cathepsin-activated fluorescent probes can detect tumors in mice and in canine patients. We previously showed that these probes can detect microscopic residual sarcoma in the tumor bed of mice during gross total resection. Many patients with soft tissue sarcoma (STS) and other tumors undergo radiation therapy (RT) before surgery. This study assesses the effect of RT on the ability of cathepsin-activated probes to differentiate between normal and cancerous tissue. Methods and Materials: A genetically engineered mouse model of STS was used to generate primary hind limb sarcomas that were treated with hypofractionated RT. Mice were injected intravenously with cathepsin-activated fluorescent probes, and various tissues, including the tumor, were imaged using a hand-held imaging device. Resected tumor and normal muscle samples were harvested to assess cathepsin expression by Western blot. Uptake of activated probe was analyzed by flow cytometry and confocal microscopy. Parallel in vitro studies using mouse sarcoma cells were performed. Results: RT of primary STS in mice and mouse sarcoma cell lines caused no change in probe activation or cathepsin protease expression. Increasing radiation dose resulted in an upward trend in probe activation. Flow cytometry and immunofluorescence showed that a substantial proportion of probe-labeled cells were CD11b-positive tumor-associated immune cells. Conclusions: In this primary murine model of STS, RT did not affect the ability of cathepsin-activated probes to differentiate between tumor and normal muscle. Cathepsin-activated probes labeled tumor cells and tumor-associated macrophages. Our results suggest that it would be feasible to include patients who have received preoperative RT in clinical studies evaluating cathepsin-activated imaging probes.

  10. A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET Imaging

    Directory of Open Access Journals (Sweden)

    Jeongsoo Yoo

    2005-01-01

    Full Text Available Dubin-Johnson syndrome (DJS is caused by a deficiency of the human canalicular multispecific organic anion transporter (cMOAT. A new lipophilic copper-64 complex of 1,4,7-tris(carboxymethyl-10-(tetradecyl-1,4,7,10-tetraazadodecane (5 was prepared and evaluated for potential as a diagnostic tool for DJS. The prepared ligand was labeled with 64Cu citrate in high radiochemical purity. In vivo uptake and clearance of the complex was determined through biodistribution studies using normal Sprague-Dawley rats and mutant cMOAT-deficient (TR− rats. In normal rats, the radioactive copper complex was cleared quickly from the body exclusively through the hepatic pathway. The 64Cu complex was taken up rapidly by the liver and quickly excreted into the small intestine and then the upper large intestine, whereas < 1% ID/organ was found in the kidney at all time points post injection. Whereas activity was accumulated continuously in the liver of TR− rats, it was not excreted into the small intestine. MicroPET studies of normal and TR rats were consistent with biodistribution data and showed dramatically different images. This study strongly suggests that cMOAT is involved in excretion of 64Cu-5. The significant difference between the biodistribution data and microPET images of the normal and TR− rats demonstrates that this new 64Cu complex may allow noninvasive diagnosis of DJS in humans.

  11. A new myocardial imaging agent: Synthesis, characterization, and biodistribution of gallium-68-BAT-TECH

    International Nuclear Information System (INIS)

    Kung, H.F.; Liu, B.L.; Mankoff, D.; Kung, M.P.; Billings, J.J.; Francesconi, L.; Alavi, A.

    1990-01-01

    In order to develop a new myocardial perfusion agent for positron emission tomography (PET), a new lipid-soluble gallium complex was evaluated. Synthesis, radiolabeling, characterization, and biodistribution of a unique gallium complex, [ 67 Ga]BAT-TECH (bis-aminoethanethiol-tetraethyl-cyclohexyl), are described. The complex formation between Ga+3 and BAT-TECH ligand is simple, rapid, and of high yield (greater than or equal to 95%). This process is amenable to kit formulation. The complex has a net charge of +1 and a Ga/ligand ratio of 1:1. Biodistribution in rats shows high uptake in the heart as well as in the liver. When [ 68 Ga] BAT-TECH was injected into a monkey, the heart and liver are clearly delineated by PET imaging, suggesting that this complex may be a possible tracer for myocardial perfusion imaging

  12. Synthesis of opioid receptor imaging agent 7α-o-IA-DPN

    International Nuclear Information System (INIS)

    Wang Rongfu

    1997-01-01

    A new opioid receptor imaging agent is designed and synthesized. 7α-o-iodoallyl diprenorphine (7α-o-IA-DPN) was obtained in one step by radioiododestannylation, which involved in the selection of DPN as an opioid antagonist, the regioselective protection of the DPN phenol tertiary-OH using acetylation and the introduction of vinylstannane as prosthetic group into the tertiary alcohol group position in the 7α-side chain. The iodinated DPN derivation was possessed of high radiolabeled yield (>90%) with 80 TBq/mmol specific radioactivity and more than 95% radiochemical purity. In vitro opioid receptor binding analysis showed very high affinity (Ki = 0.4 nmol/L). This new radioiodinated opioid ligand is suitable for SPECT study of opioid receptor imaging

  13. Development of NMR imaging using CEST agents: application to brain tumor in a rodent model

    International Nuclear Information System (INIS)

    Flament, J.

    2012-01-01

    The study aimed at developing saturation transfer imaging of lipoCEST contrast agents for the detection of angiogenesis in a U87 mouse brain tumor model. A lipoCEST with a sensitivity threshold of 100 pM in vitro was optimized in order to make it compatible with CEST imaging in vivo. Thanks to the development of an experimental setup dedicated to CEST imaging, we evaluated lipoCEST to detect specifically tumor angiogenesis. We demonstrated for the first time that lipoCEST visualization was feasible in vivo in a mouse brain after intravenous injection. Moreover, the integrin α v β 3 over expressed during tumor angiogenesis can be specifically targeted using a functionalized lipoCEST with RGD peptide. The specific association between the RGD-lipoCEST and its target α v β 3 was confirmed by immunohistochemical data and fluorescence microscopy. Finally, in order to tend to a molecular imaging protocol by CEST-MRI, we developed a quantification tool of lipoCEST contrast agents. This tool is based on modeling of proton exchange processes in vivo. By taking into account both B0 and B1 fields inhomogeneities which can dramatically alter CEST contrast, we showed that the accuracy of our quantification tool was 300 pM in vitro. The tool was applied on in vivo data acquired on the U87 mouse model and the maximum concentration of RGD-lipoCEST linked to their molecular targets was evaluated to 1.8 nM. (author) [fr

  14. Complications from the use of intravenous gadolinium-based contrast agents for magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Elias Junior, Jorge; Santos, Antonio Carlos dos; Nogueira-Barbosa, Marcello Henrique; Muglia, Valdair Francisco; Koenigkam-Santos, Marcel [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Hospital das Clinicas. Centro de Ciencias das Imagens e Fisica Medica]. E-mail: jejunior@fmrp.usp.br

    2008-07-15

    Gadolinium-based contrast agents are much safer than the iodinated ones; however complications may occur and should be recognized for appropriate orientation and management. The total incidence of adverse reactions to contrast agents in magnetic resonance imaging ranges between 2% and 4%. Cases of severe acute reactions to gadolinium, such as laryngospasm and anaphylactic shock, are rare. Chronic complications secondary to the use of gadolinium also can occur and, recently an association between its use and a rare dermatologic disease occurring in patients with renal failure has been reported. Nephrogenic systemic fibrosis was the subject of an official health notification issued by the American Food and Drug Administration. This progressive disease is characterized by hardened skin with fibrotic nodules and plaques which may involve other parts of the body. Patients who have been affected by this disorder presented chronic renal failure, with metabolic acidosis and had been submitted to magnetic resonance angiography, probably involving exposure to large amounts of intravenous paramagnetic contrast. This review is aimed at presenting a succinct description of the gadolinium-based contrast agent types, possible secondary complications, their preventive measures and management. (author)

  15. PEGylated chitosan grafted with polyamidoaminedendron as tumor-targeted magnetic resonance imaging contrast agent

    International Nuclear Information System (INIS)

    Guangyue Zu; Xiaoyan Tong; Yi Cao; Ye Kuang; Yajie Zhang; Min Liu; Renjun Pei

    2017-01-01

    Macromolecular contrast agents labeled with targeting ligands are now receiving growing interest in tumor-targeted magnetic resonance imaging. In this study, a macromolecular contrast agent based on PEGylated chitosan was synthesized and characterized, and its application as an MRI contrast agent was then demonstrated both in vitro and in vivo. First, the chitosan backbone was partially grafted with poly(ethylene glycol), which was used to improve the in vivo stability, followed by modifying with azide groups. Second, alkynyl-terminated PAMAM dendron modified with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) was synthesized and conjugated onto the chitosan backbone through click chemistry. Finally, the obtained mCA was further functionalized with folic acid to improve the target specificity. The obtained FA labeled mCA exhibited higher relaxivity (9.53 mM"-"1.s"-"1) relative to Gd-DTPA (4.25 mM"-"1.s"-"1) and showed negligible toxicity as determined by the WST assay. In vivo MRI results suggested that a relatively high signal enhancement was observed in the tumor region, which made it a promising candidate for tumor-targeted MRI CA. (authors)

  16. Preparation, purification and primary bioevaluation of radioiodinated ofloxacin. An imaging agent

    International Nuclear Information System (INIS)

    Kandil, Shaban; Seddik, Usama; Hussien, Hiba; Shaltot, Mohamed; El-Tabl, Abdou

    2015-01-01

    The broad-spectrum antibiotic agents have been demonstrated as promising diagnostic tools for early detection of infectious lesions. We set out ofloxacin (Oflo), a second-generation fluoroquinolone, for the radioiodination process. In particular, this was carried out with 125 I via an electrophilic substitution reaction. The radiochemical yield was influenced by different factors; drug concentration, different oxidizing agents, e.g. chloramine-T, iodogen and n-bromosuccinimide, pH of medium, reaction time, temperature and different organic media. These parameters were studied to optimize the best conditions for labeling with ofloxacin. We found that radiolabeling in ethanol medium showed a 70% radiochemical yield of 125 I-ofloxacin. The radioiodination was determined by means of TLC and HPLC. The cold labeled Oflo ( 127 I-Oflo) was prepared and controlled by HPLC. The cold labeled Oflo was also confirmed by NMR and MS techniques. Furthermore, biodistribution studies for labeled 125 I-Oflo were examined in two independent groups (3 mice in each one); control and E. Coli-injected (inflamed). The radiotracer showed a good localization in muscle of thigh for inflamed group as compared to control. In conclusion, ofloxacine might be a promising target as an anti-inflammatory imaging agent.

  17. Preparation, purification and primary bioevaluation of radioiodinated ofloxacin. An imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Kandil, Shaban; Seddik, Usama; Hussien, Hiba; Shaltot, Mohamed [Atomic Energy Authority, Cairo (Egypt). Cyclotron Project; El-Tabl, Abdou [Monofia Univ. (Egypt). Faculty of Science

    2015-07-01

    The broad-spectrum antibiotic agents have been demonstrated as promising diagnostic tools for early detection of infectious lesions. We set out ofloxacin (Oflo), a second-generation fluoroquinolone, for the radioiodination process. In particular, this was carried out with {sup 125}I via an electrophilic substitution reaction. The radiochemical yield was influenced by different factors; drug concentration, different oxidizing agents, e.g. chloramine-T, iodogen and n-bromosuccinimide, pH of medium, reaction time, temperature and different organic media. These parameters were studied to optimize the best conditions for labeling with ofloxacin. We found that radiolabeling in ethanol medium showed a 70% radiochemical yield of {sup 125}I-ofloxacin. The radioiodination was determined by means of TLC and HPLC. The cold labeled Oflo ({sup 127}I-Oflo) was prepared and controlled by HPLC. The cold labeled Oflo was also confirmed by NMR and MS techniques. Furthermore, biodistribution studies for labeled {sup 125}I-Oflo were examined in two independent groups (3 mice in each one); control and E. Coli-injected (inflamed). The radiotracer showed a good localization in muscle of thigh for inflamed group as compared to control. In conclusion, ofloxacine might be a promising target as an anti-inflammatory imaging agent.

  18. Characterization of image heterogeneity using 2D Minkowski functionals increases the sensitivity of detection of a targeted MRI contrast agent.

    Science.gov (United States)

    Canuto, Holly C; McLachlan, Charles; Kettunen, Mikko I; Velic, Marko; Krishnan, Anant S; Neves, Andre' A; de Backer, Maaike; Hu, D-E; Hobson, Michael P; Brindle, Kevin M

    2009-05-01

    A targeted Gd(3+)-based contrast agent has been developed that detects tumor cell death by binding to the phosphatidylserine (PS) exposed on the plasma membrane of dying cells. Although this agent has been used to detect tumor cell death in vivo, the differences in signal intensity between treated and untreated tumors was relatively small. As cell death is often spatially heterogeneous within tumors, we investigated whether an image analysis technique that parameterizes heterogeneity could be used to increase the sensitivity of detection of this targeted contrast agent. Two-dimensional (2D) Minkowski functionals (MFs) provided an automated and reliable method for parameterization of image heterogeneity, which does not require prior assumptions about the number of regions or features in the image, and were shown to increase the sensitivity of detection of the contrast agent as compared to simple signal intensity analysis. (c) 2009 Wiley-Liss, Inc.

  19. New 68Ga-PhenA bisphosphonates as potential bone imaging agents

    International Nuclear Information System (INIS)

    Wu, Zehui; Zha, Zhihao; Choi, Seok Rye; Plössl, Karl; Zhu, Lin; Kung, Hank F.

    2016-01-01

    Introduction: In vivo positron emission tomography (PET) imaging of the bone using [ 68 Ga]bisphosphonates may be a valuable tool for cancer diagnosis and monitoring therapeutic treatment. We have developed new [ 68 Ga]bisphosphonates based on the chelating group, AAZTA (6-[bis(hydroxycarbonyl-methyl)amino]-1,4-bis(hydroxycarbonyl methyl)-6-methylperhydro-1,4-diazepine). Method: Phenoxy derivative of AAZTA (2,2′-(6-(bis(carboxymethyl)amino)-6-((4-(2-carboxyethyl)phenoxy) methyl)-1,4-diazepane-1,4-diyl)diacetic acid), PhenA, 2, containing a bisphosphonate group (PhenA-BPAMD, 3, and PhenA-HBP, 4) was prepared. Labeling of these chelating agents with 68 Ga was evaluated. Results: The ligands reacted rapidly in a sodium acetate buffer with [ 68 Ga]GaCl 3 eluted from a commercially available 68 Ge/ 68 Ga generator (pH 4, > 95% labeling at room temperature in 5 min) to form [ 68 Ga]PhenA-BPAMD, 3, and [ 68 Ga]PhenA-HBP, 4. The improved labeling condition negates the need for further purification. The 68 Ga bisphosphonate biodistribution and autoradiography of bone sections in normal mice after an iv injection showed excellent bone uptake. Conclusion: New 68 Ga labeled bisphosphonates may be useful as in vivo bone imaging agents in conjunction with positron emission tomography (PET).

  20. Preparation and evaluation of (131I)AgI particles: potential lungs perfusion imaging agent

    International Nuclear Information System (INIS)

    Chattopadhyay, Sankha; Das, Sujata Saha; Sinha, Samarendu; Sarkar, Bharat Ranjan; Ganguly, Shantanu; Chandra, Susmita; De, Kakali; Mishra, Mridula

    2010-01-01

    Since the discovery of iodine-131 (t 1/2 : 8 d) by Livingood and Seaborg (1938), this, and other radioisotopes of iodine, have found widespread use in nuclear medicine. The purpose of the present work was to formulate Ag 131 I particles and bio-evaluate the same. The Ag 131 I particles were prepared in acidic condition having 100% R.C. Purity. The biological evaluation of Ag 131 1 particles was made by injecting about 111-185 MBq of Ag 131 I particles preparations in female albino rabbits (2-2.5 kg weight) intravenously by femoral vein under urethane anesthesia. Imaging studies were performed under Gamma Camera. The entire amount of the Ag 131 I particles were found to deposit in the lungs and remained there almost unchanged for a certain period of time after the intervenous administration. The images showed excellent, uniform lung uptake with no interference from liver and spleen to the lower regions of right and left lobes. It showed a high accumulation in the rabbits lungs (>99%) and remained constant for at least for 20 min. It is also worthy to study with 123 I/ 124 I labelled AgI for lung imaging study. In conclusion, the synthetic radiopharmaceutical ( 131 I)-Silver iodide colloid can be prepared with a large particle size, in a simple and practical manner, and it has good potential for use as a perfusion imaging agent in lung scans

  1. Preclinical Assessment of a 68Ga-DOTA-Functionalized Depsipeptide as a Radiodiagnostic Infection Imaging Agent.

    Science.gov (United States)

    Ebenhan, Thomas; Mokaleng, Botshelo Brenda; Venter, Jacobus Daniel; Kruger, Hendrik Gert; Zeevaart, Jan Rijn; Sathekge, Mike

    2017-08-24

    The study assessed a radiolabeled depsipeptide conjugate ( 68 Ga-DOTA-TBIA101) for its potential as an imaging agent targeting infection or infection-associated inflammation. 68 Ga-labeled DOTA-TBIA101 imaging was performed in (NZR1) healthy rabbits; (NZR2) rabbits bearing muscular sterile inflammation and Staphylococcus aureus (SA) infection; and (NZR3) rabbits infected with Mycobacterium tuberculosis (MTB) combined with a subcutaneous scruff infection of SA in the same animal. All animals were imaged using a PET/CT scanner at 5 and 60 min post injection. Images showed elevated accumulation of 68 Ga-DOTA-TBIA101 in the sterile muscular inflammation site (T/NT ratio = 2.6 ± 0.37 (5 min) and 2.8 ± 2.3 (60 min)) and muscles infected with MTB (T/NT ratio = 2.6 ± 0.35 (5 min) and 2.8 ± 0.16 (60 min)). The findings suggest that 68 Ga-DOTA-TBIA101-PET/CT may detect MTB-associated inflammation, although more foundational studies need to be performed to rationalize the diagnostic value of this technique.

  2. sup(99m)Tc-labeled monofluorophosphate as a skeletal imaging agent

    International Nuclear Information System (INIS)

    Ichikawa, Tsuneji; Ito, Yasuhiko; Muranaka, Akira; Yokobayashi, Tsuneo; Uchida, Masahiro

    1976-01-01

    The performance of sup(99m)Tc-monofluorophosphate was compared with those of sup(99m)Tc-pyrophosphate and sup(99m)Tc-diphosphonate in rabbits. Studies included chromatographic quality control, measurements of blood clearance, tissue distribution, urinary excretion, skeletal imaging, and measurements of the serum calcium. The labeling for sup(99m)Tc-monofluorophosphate was 98% on paper chromatography and 85% on thin layer chromatography. A large fraction of the activity of the three labeled agents was cleared very rapidly from the bloodstream: however, slow components of the curves were the highest for sup(99m)Tc-monofluorophosphate and lowest for sup(99m)Tc-diphosphonate. Three hours after injection 20% of the dose of sup(99m)Tc-monofluorophosphate was taken up by bone. The corresponding values of sup(99m)Tc-pyrophosphate and sup(99m)Tc-diphosphonate were 29.1% and 40.0% respectively. Ratio of concentration in bone to that in other major organs was highest with sup(99m)Tc-diphosphonate. Ratios were similar for both sup(99m)Tc-monofluorophosphate and sup(99m)Tc-pyrophosphate and much lower than those of sup(99m)Tc-diphosphonate. No significant differences were demonstrated in urinary excretion of the three labeled agents. Visual comparison of the scans obtained with three compounds confirmed the results of radioassay. All were excellent skeletal imaging agents, although sup(99m)Tc-diphosphonate appeared to be superior to the other two mainly because of a higher target to non-target ratio. With 50 mg of monofluorophosphate and 1 mg of stannous fluoride, no hypocalcemia was observed. (J.P.N.)

  3. Study on folate receptor PET imaging agent 18F-flurophenethyl folate

    International Nuclear Information System (INIS)

    Guo Congying; Zhu Jianhua; Qian Jun; Yang Yang; Shen Haixing; Zhang Zhengwei

    2009-01-01

    This work is aimed at synthesizing an 18 F-labelled folate derivative that can be used as folate-receptor induced tumor PET imaging agent. Under the optimal reaction and testing specification formulated during the cold-labeling experiments, 18 F labeling of folic acid was achieved in three steps of 18 F pre-labeling,bromination and esterification. The receptor binding property of the newly-synthesized folate radio-derivative was studied through β-lactoglobulin binding test. Tumor-bearing nude mice injected with the new compound were used to study whether the derivative can accumulate within tumor issue. Preliminary studies in vitro and in vivo showed that this new PET agent still possessed receptor binding qualities of folic acid. 18 F-flurophenethyl folate remained good affinity and specificity with β-lactoglobulin. Accumulation of activities in tumor tissues was found in tumor-bearing nude mice. A new folate receptor ligand: 18 F-flurophenethyl folate was synthesized,with high yield and good stability. Since the pre-labeling method was used, the fluorine labeling was not directly imposed upon folic acid.In this way, the structure destruction, which happens in high temperature reaction of folic acid, can be avoided. The synthesized folate derivative remained the binding structural quality of folic acid and could bind with the folate-binding protein: β-lactoglobulin. Through the folate receptors located on tumor tissues, 18 F-flurophenethyl folate accumulated in the tumor tissue, exhibiting its potential as a tumor PET imaging agent. (authors)

  4. Performance characteristics of magnetic resonance imaging without contrast agents or sedation in pediatric appendicitis.

    Science.gov (United States)

    Didier, Ryne A; Hopkins, Katharine L; Coakley, Fergus V; Krishnaswami, Sanjay; Spiro, David M; Foster, Bryan R

    2017-09-01

    Magnetic resonance imaging (MRI) has emerged as a promising modality for evaluating pediatric appendicitis. However optimal imaging protocols, including roles of contrast agents and sedation, have not been established and diagnostic criteria have not been fully evaluated. To investigate performance characteristics of rapid MRI without contrast agents or sedation in the diagnosis of pediatric appendicitis. We included patients ages 4-18 years with suspicion of appendicitis who underwent rapid MRI between October 2013 and March 2015 without contrast agent or sedation. After two-radiologist review, we determined performance characteristics of individual diagnostic criteria and aggregate diagnostic criteria by comparing MRI results to clinical outcomes. We used receiver operating characteristic (ROC) curves to determine cut-points for appendiceal diameter and wall thickness for optimization of predictive power, and we calculated area under the curve (AUC) as a measure of test accuracy. Ninety-eight MRI examinations were performed in 97 subjects. Overall, MRI had a 94% sensitivity, 95% specificity, 91% positive predictive value and 97% negative predictive value. Optimal cut-points for appendiceal diameter and wall thickness were ≥7 mm and ≥2 mm, respectively. Independently, those cut-points produced sensitivities of 91% and 84% and specificities of 84% and 43%. Presence of intraluminal fluid (30/33) or localized periappendiceal fluid (32/33) showed a significant association with acute appendicitis (Pappendicitis when multiple diagnostic criteria are considered in aggregate. Individual diagnostic criteria including optimized cut-points of ≥7 mm for diameter and ≥2 mm for wall thickness demonstrate high sensitivities but relatively low specificities. Nonvisualization of the appendix favors a negative diagnosis.

  5. Exogenous contrast agents for thermoacoustic imaging: An investigation into the underlying sources of contrast

    International Nuclear Information System (INIS)

    Ogunlade, Olumide; Beard, Paul

    2015-01-01

    Purpose: Thermoacoustic imaging at microwave excitation frequencies is limited by the low differential contrast exhibited by high water content tissues. To overcome this, exogenous thermoacoustic contrast agents based on gadolinium compounds, iron oxide, and single wall carbon nanotubes have previously been suggested and investigated. However, these previous studies did not fully characterize the electric, magnetic, and thermodynamic properties of these agents thus precluding identification of the underlying sources of contrast. To address this, measurements of the complex permittivity, complex permeability, DC conductivity, and Grüneisen parameter have been made. These measurements allowed the origins of the contrast provided by each substance to be identified. Methods: The electric and magnetic properties of the contrast agents were characterized at 3 GHz using two rectangular waveguide cavities. The DC conductivity was measured separately using a conductivity meter. Thermoacoustic signals were then acquired and compared to those generated in water. Finally, 3D electromagnetic simulations were used to decouple the different contributions to the absorbed power density. Results: It was found that the gadolinium compounds provided appreciable electric contrast but not originating from the gadolinium itself. The contrast was either due to dissociation of the gadolinium salt which increased ionic conductivity or its nondissociated polar fraction which increased dielectric polarization loss or a combination of both. In addition, very high concentrations were required to achieve appreciable contrast, to the extent that the Grüneisen parameter increased significantly and became a source of contrast. Iron oxide particles were found to produce low but measurable dielectric contrast due to dielectric polarization loss, but this is attributed to the coating of the particles not the iron oxide. Single wall carbon nanotubes did not provide measurable contrast of any type

  6. Exogenous contrast agents for thermoacoustic imaging: An investigation into the underlying sources of contrast

    Energy Technology Data Exchange (ETDEWEB)

    Ogunlade, Olumide, E-mail: o.ogunlade@ucl.ac.uk; Beard, Paul [Department of Medical Physics and Biomedical Engineering, University College London, London WC1E 6BT (United Kingdom)

    2015-01-15

    Purpose: Thermoacoustic imaging at microwave excitation frequencies is limited by the low differential contrast exhibited by high water content tissues. To overcome this, exogenous thermoacoustic contrast agents based on gadolinium compounds, iron oxide, and single wall carbon nanotubes have previously been suggested and investigated. However, these previous studies did not fully characterize the electric, magnetic, and thermodynamic properties of these agents thus precluding identification of the underlying sources of contrast. To address this, measurements of the complex permittivity, complex permeability, DC conductivity, and Grüneisen parameter have been made. These measurements allowed the origins of the contrast provided by each substance to be identified. Methods: The electric and magnetic properties of the contrast agents were characterized at 3 GHz using two rectangular waveguide cavities. The DC conductivity was measured separately using a conductivity meter. Thermoacoustic signals were then acquired and compared to those generated in water. Finally, 3D electromagnetic simulations were used to decouple the different contributions to the absorbed power density. Results: It was found that the gadolinium compounds provided appreciable electric contrast but not originating from the gadolinium itself. The contrast was either due to dissociation of the gadolinium salt which increased ionic conductivity or its nondissociated polar fraction which increased dielectric polarization loss or a combination of both. In addition, very high concentrations were required to achieve appreciable contrast, to the extent that the Grüneisen parameter increased significantly and became a source of contrast. Iron oxide particles were found to produce low but measurable dielectric contrast due to dielectric polarization loss, but this is attributed to the coating of the particles not the iron oxide. Single wall carbon nanotubes did not provide measurable contrast of any type

  7. An agent harms a victim: A functional magnetic resonance imaging study on specific moral emotions

    Energy Technology Data Exchange (ETDEWEB)

    Kedia, G. [INSERM, Inst Hlth et Med Res, U797, Res Unit Neuroimaging Psychiat, F-91401 Orsay (France); Kedia, G.; Martinot, J.L. [CEA, DSV, I2BM, SHFJ, Orsay (France); Kedia, G.; Martinot, J.L. [Univ Paris Sud, U797, Paris (France); Kedia, G.; Hilton, D. [Univ Toulouse, Toulouse (France); Berthoz, S. [Paris Descartes Univ, U797, Paris (France); Wessa, M. [Univ Heidelber, Cent Inst Mental Hlth, D-6800 Mannheim (Germany)

    2008-07-01

    The statement 'An agent harms a victim' depicts a situation that triggers moral emotions. Depending on whether the agent and the victim are the self or someone else, it can lead to four different moral emotions: self-anger ('I harm myself'), guilt ('I harm someone'), other-anger ('someone harms me'), and compassion ('someone harms someone'). In order to investigate the neural correlates of these emotions, we examined brain activation patterns elicited by variations in the agent (self vs. other) and the victim (self vs. other) of a harmful action. Twenty-nine healthy participants underwent functional magnetic resonance imaging while imagining being in situations in which they or someone else harmed themselves or someone else. Results indicated that the three emotional conditions associated with the involvement of other, either as agent or victim (guilt, other-anger, and compassion conditions), all activated structures that have been previously associated with the Theory of Mind (ToM, the attribution of mental states to others), namely, the dorsal medial prefrontal cortex, the precuneus, and the bilateral temporo-parietal junction. Moreover, the two conditions in which both the self and other were concerned by the harmful action (guilt and other-anger conditions) recruited emotional structures (i. e., the bilateral amygdala, anterior cingulate, and basal ganglia). These results suggest that specific moral emotions induce different neural activity depending on the extent to which they involve the self and other. (authors)

  8. Preclinical pharmacological studies of 99Tcm-TRODAT-1 as a dopamine transporter imaging agent

    International Nuclear Information System (INIS)

    Fang Ping; Wan Weixing; Liu Zhenguo; Wu Chunying; Chen Shengdi; Chen Zhengping; Zhou Xiang; Ji Shuren

    2001-01-01

    Objective: To develop a 99 Tc m labelled dopamine transporter (DAT) imaging agent, 99 Tc m -TRODAT-1 [TRODAT-1: 2β-([N,N'-bis(2-mercaptoethyl) ethylene diamino] methyl), 3β-(4-chlorophenyl) tropane], for evaluating the variation of DAT in patients with Parkinson's disease. Methods: 99 Tc m -TRODAT-1 was successfully prepared on a kit basis. Preclinical pharmacological studies were performed in rats, mice, rabbits, monkeys and a volunteer with diagnosed Parkinson disease (PD). Results: Radiochemical purity of 99 Tc m -TRODAT-1 was over 90%, and remained stable for 6 hours. The specific uptake in striatum was significantly diminished, from 3.45 to 0.12 at 2 h by pretreating rats with a dose of DAT competing ligand, β-CIT [1 mg/kg, 2β-carbomethoxy-3β-(4-iodophenyl) tropane]. Blood clearance kinetics was studied in rabbits, and the initial half-life was of 1.2 min, the elimination half-life was of 368 min. Images of normal monkey's brain exhibited an excellent accumulation in basal ganglia region, where dopamine neurons were concentrated. In hemi parkinsonism model monkeys, the ratio of normal ST/CB and lesioned ST/CB were 1.56 and 0.94, respectively. Brain imaging studies in volunteer indicated that uptake and retention in the basal ganglia, the ratio of normal striatal uptake to lesioned one's was 1.15 measured by SPECT imaging at 2 h. The result of imaging was conformable with his clinical symptoms. Conclusions: The stable, neutral and lipophilic complex, 99 Tc m -TRODAT-1, can be accumulated in the striatal area, where DAT is concentrated, high quality images can be obtained. It suggests that 99 Tc m -TRODAT-1 might be a safe and effective tracer for monitoring the variation in DAT which is associated with various neurodegenerative diseases

  9. A tri-modal molecular imaging agent for sentinel lymph node mapping

    International Nuclear Information System (INIS)

    Qin, Zhengtao; Hoh, Carl K.; Hall, David J.; Vera, David R.

    2015-01-01

    Introduction: We report an “instant kit” method to radiolabel fluorescent-tilmanocept with 68 Ga and 99m Tc for tri-modal molecular imaging of sentinel lymph nodes (SLNs). Methods: Solutions of sodium acetate, 68 GaCl 3 and Na 99m TcO 4 were added successively to a “kit vial” containing lyophilized 800CW-tilmanocept, SnCl 2 , trehalose and ascorbic acid. After a 30-min incubation, the pH was neutralized with PBS. No purification was required. Radiochemical and fluorescence purity was measured by HPLC and ITLC techniques. In vitro stability was measured by standing gel chromatography (SGC) and ITLC by a 100-fold dilution 0.25 h after radiolabeling. In vivo stability was measured by SGC and ITLC after an 11 h incubation in human plasma. A dose (0.1 nmol, ~ 1 MBq 68 Ga, ~ 25 MBq 99m Tc) was injected to the footpad of 4 mice. Popliteal SLNs were imaged by PET and fluorescence imaging systems at 0.5, 24, 48, 72 h, then excised and assayed for 99m Tc. Results: Radiochemical and fluorescent purity exceeded 98%. The in vitro stability assay demonstrated high irreversibility of both radiolabels and the fluorescent label, and in vivo stability assay demonstrated high stability of the technetium and fluorescent labels to plasma metabolism. Popliteal SLNs were identified by PET and fluorescence imaging within 0.5 h of injection. SLN fluorescence intensity remained constant for 72 h, when ~ 1% of the injected dose resided in the SLN. Conclusions: Fluorescent-labeled tilmanocept can be radiolabeled with 68 Ga and 99m Tc by the sequential addition of each generator eluate to a lyophilized kit. The resulting tri-modal agent provides: PET images for pre-operative SLN mapping, fluorescence imaging up to 72 hours after injection, and quantitative radiometric measurement of SLN accumulation after excision.

  10. Cardiac biomarkers in neonatal hypoxic ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, D

    2012-04-01

    Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

  11. Preparation and animal studies of 99Tcm-TRODAT-1 as a dopamine transporter imaging agent

    International Nuclear Information System (INIS)

    Fang Ping; Wu Chunying; Chen Zhengping; Zhou Xiang; Wan Weixing; Ji Shuren

    1999-01-01

    Objective: To develop 99 Tc m labelled dopamine transporter (DAT) imaging agent 99 Tc m -(2β-[N,N'-bis(2-mercaptoethyl) ethylenediamin] methyl, 3β-(4-chlorophenyl) tropane (TRODAT-1) for evaluating changes of DAT in patients with Parkinson's disease. Methods: TRODAT-1 was synthesized from cocaine by stepwise reactions adding two aminoethanethiol units. Using SnCl 2 as reducing agent, and in the presence of Naglucoheptonate, 99 Tc m -TRODAT-1 was prepared. Animal studies have been performed in rats and normal monkeys. Results: The structure of TRODAT-1 was confirmed by IR, 1 HNMR and MS. Radiochemical purity of 99 Tc m -TRODAT-1 was over 90%, and stable for 24 h at room temperature. The partition coefficient in octanol and buffer was 132 and 154 at pH 7.0 and 7.4 respectively. Biodistribution displayed relatively low uptake in rat brain (0.28 and 0.12% ID/org at 2 min and 60 min post injection, respectively), but high uptake in liver (16.7% ID/organ at 60 min), steady uptake in kidney (maintained 3% ID/organ). The major radioactivity was excreted by hepatobiliary systems. The distribution in rat's brain showed that striatal uptake were 0.193, 0.189, 0.142 and 0.136% ID/g at 2, 30, 60 and 120 min, respectively. The ratios of striatal to cerebellar, striatal to hippocampal and striatal to cortical were 4.45 2.55 and 3.15 at 120 min post injection, respectively. Brain image studies in monkeys indicated that TRODAT was uptake and retained in the basal ganglia, where containing DAT abundantly. Ratio of regional brain uptakes of striatum/cerebellum was 1.56 as measured by SPECT imaging at 120 min. Conclusions: Above results showed the stable, neutral and lipophilic complex 99 Tc m -TRODAT-1 can cross the blood brain barrier, and be selectively concentrated by the striatal area, where containing DAT abundantly. High quality images of monkeys were also obtained. It suggested that 99 Tc m -TRODAT-1 may be a promising agent for clinical application

  12. Tissue-specific MR contrast agents. Impact on imaging diagnosis and future prospects

    International Nuclear Information System (INIS)

    Yoshimitsu, Kengo; Nakayama, Tomohiro; Kakihara, Daisuke; Irie, Hiroyuki; Tajima, Tsuyoshi; Asayama, Yoshiki; Hirakawa, Masakazu; Ishigami, Kousei; Honda, Hiroshi

    2005-01-01

    tumor vascularity and precise location. Unfortunately, however, its performance in depicting tumor vascularity was suggested to be less than that of multi detector row CT (MDCT) or dynamic MR using Gd-DTPA. Further investigation is needed to determine the true usefulness of Gd-EOB-DTPA in the imaging diagnosis of liver tumors. A number of other promising tissue-specific contrast agents currently are under development, including blood pool agents, lymphatic or lymph nodal agents, blood vessel wall agents, and so on. We, as radiologists, should keep in mind that the true efficacy and roles of these tissue-specific agents need to be evaluated not only from the viewpoint of diagnostic accuracy but also with reference to their socioeconomic aspects, particularly in this era of the Diagnosis-Related Group/Prospective Payment System. (author)

  13. Pharmacological experiment of 13N-ammonia as PET imaging agent

    International Nuclear Information System (INIS)

    Wang Mingfang; Tang Ganghua; Gao Xiao; Li Zhi; Wu Hubing; Huang Zuhan; Jiang Hong; Zhong Jinmei; Wang Quanshi

    2002-01-01

    . 13 N-ammonia is an ideal myocardial blood flow perfusion imaging agent. rMBF can be measured accurately and noninvasively by 13 N-ammonia dynamic and static PET imaging

  14. Antibiofouling polymer coated gold nanoparticles as a dual modal contrast agent for X-ray and photoacoustic imaging

    International Nuclear Information System (INIS)

    Guojia Huang; Yi Yuan; Xing Da

    2011-01-01

    X-ray is one of the most useful diagnostic tools in hospitals in terms of frequency of use and cost, while photoacoustic (PA) imaging is a rapidly emerging non-invasive imaging technology that integrates the merits of high optical contrast with high ultrasound resolution. In this study, for the first time, we used gold nanoparticles (GNPs) as a dual modal contrast agent for X-ray and PA imaging. Soft gelatin phantoms with embedded tumor simulators of GNPs in various concentrations are clearly shown in both X-ray and PA imaging. With GNPs as a dual modal contrast agent, X-ray can fast detect the position of tumor and provide morphological information, whereas PA imaging has important potential applications in the image guided therapy of superficial tumors such as breast cancer, melanoma and Merkel cell carcinoma.

  15. Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents

    Directory of Open Access Journals (Sweden)

    Jackson AW

    2015-09-01

    Full Text Available Alexander W Jackson,1,* Prashant Chandrasekharan,2,* Jian Shi,3 Steven P Rannard,4 Quan Liu,5 Chang-Tong Yang,6 Tao He1,7 1Institute of Chemical and Engineering Sciences (ICES, 2Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A* STAR, 3Department of Biological Science, National University of Singapore, Singapore; 4Department of Chemistry, University of Liverpool, Liverpool, United Kingdom; 5School of Chemical and Biomedical Engineering, 6Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 7School of Chemistry and Chemical Engineering, HeFei University of Technology, Anhui, People’s Republic of China *These authors contributed equally to this work Abstract: Branched copolymer nanoparticles (Dh =20–35 nm possessing 1,4,7, 10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid macrocycles within their cores have been synthesized and applied as magnetic resonance imaging (MRI nanosized contrast agents in vivo. These nanoparticles have been generated from novel functional monomers via reversible addition–fragmentation chain transfer polymerization. The process is very robust and synthetically straightforward. Chelation with gadolinium and preliminary in vivo experiments have demonstrated promising characteristics as MRI contrast agents with prolonged blood retention time, good biocompatibility, and an intravascular distribution. The ability of these nanoparticles to perfuse and passively target tumor cells through the enhanced permeability and retention effect is also demonstrated. These novel highly functional nanoparticle platforms have succinimidyl ester-activated benzoate functionalities within their corona, which make them suitable for future peptide conjugation and subsequent active cell-targeted MRI or the conjugation of fluorophores for bimodal imaging. We have also demonstrated that these branched copolymer nanoparticles are able to noncovalently

  16. 99mTc-Alafosfalin: an antibiotic peptide infection imaging agent

    International Nuclear Information System (INIS)

    Tsopelas, C.; Penglis, S.; Ruszkiewicz, A.; Bartholomeusz, F.D.L.

    2003-01-01

    The radiolabeled antibiotic peptide 99m Tc-alafosfalin was assessed as an infection imaging agent in a rat model by comparison with 99m Tc-DTPA and 99m Tc-leukocytes. 99m Tc-alafosfalin was prepared via an instant cold kit and 99m Tc-leukocytes were prepared using 99m Tc-stannous fluoride colloid in an ex vivo labeling procedure of whole blood. In separate experiments, the three radiotracers were administered to rats infected with staphylococcus aureus. Quantitative biodistribution studies were performed as well as scintigraphic images and histopathology. 99m Tc-alafosfalin is a stable product, obtained in high radiochemical purity (>95%). This agent was mainly renally excreted, with low liver, spleen and bone uptake, and resulted in a mean ratio of infected/non-infected thighs of 4.3/1.0 at 4 hr post radiotracer injection. 99m Tc-DTPA gave a corresponding ratio of 1.9/1.0 and 99m Tc-leukocytes gave 20.0/1.0 at the same time point. An in vitro assay found the level of 99m Tc-alafosfalin binding to staphylococcus aureas higher than 99m Tc-DTPA (10% versus 1% respectively). 99m Tc-alafosfalin accumulates at sites of infection in a rat model better than the perfusion molecule 99m Tc-DTPA, yet less than 99m Tc-leukocytes. The distribution characteristics of this 99m Tc-antibiotic peptide would be an advantage in imaging abdominal and soft tissue infection

  17. Metal-oxo containing polymer nanobeads as potential contrast agents for magnetic resonance imaging

    Science.gov (United States)

    Pablico, Michele Huelar

    Magnetic resonance imaging (MRI) has greatly revolutionized the way diseases are detected and treated, as it is a non-invasive imaging modality solely based on the interaction of radiowaves and hydrogen nuclei in the presence of an external magnetic field. It is widely used today for the diagnosis of diseases as it offers an efficient method of mapping structure and function of soft tissues in the body. Most MRI examinations utilize paramagnetic materials known as contrast agents, which enhance the MR signal by decreasing the longitudinal (T1) and transverse (T2) relaxation times of the surrounding water protons in biological systems. This results into increased signal intensity differences thereby allowing better interpretation and analysis of pathological tissues. Contrast agents function by lowering the T1 or lowering the T2, resulting into bright and dark contrasts, respectively. The most common MRI contrast agents that are in clinical use today are gadolinium chelates and superparamagnetic iron oxide nanoparticles, both of which have their own advantages in terms of contrast enhancement properties. In the past few years, however, there has been interest in utilizing metal-containing clusters for MRI contrast enhancement as these materials bridge the gap between the constrained structure and magnetic properties of the gadolinium chelates with the superparamagnetic behavior of the iron oxide nanoparticles. Recently, metallic clusters containing Mn and Fe metal centers have received increased attention mainly because of their potential for high spin states and benign nature. In the quest to further develop novel imaging agents, this research has focused on investigating the use of metal-oxo clusters as potential contrast agents for MRI. The primary goal of this project is to identify clusters that meet the following criteria: high paramagnetic susceptibility, water-soluble, stable, cheap, contain environmentally benign metals, and easily derivatized. This work is

  18. Diagnostic value of β amyloid plaques imaging agent 131I-IMPY brain imaging in early Alzheimer's disease

    International Nuclear Information System (INIS)

    Ye Wanzhong; Lu Chunxiong; Yang Min; Bao Jiandong; Cheng Zhaohuo; Cai Deliang; Wang Zhiqiang; Yang Bixiu

    2012-01-01

    Objective: To evaluate the diagnostic value of β-amyloid plaques imaging agent [ 131 I] 2( 4-dimethylaminop henyl)-6-iodoimidazo [1, 2-α] pyridine ( 131 I-IMPY) SPECT imaging in early Alzheimer's Disease. Methods: 24 cases of AD (7 males, 17 females, aged 48∼79 years) and 14 normal (6 males, 8 females, aged 42∼67 years) control subjects were selected for this study. 131 I-IMPY SPECT imaging was carried out 2-3 h post injection. 131 I-IMPY uptake defined as the ratio of each brain gyrus and cerebellum uptake on fixed region of interest (ROI) (Rcl/cb) was calculated. Comparative analysis between the two groups was carried out using t-test. Results: In patients with early AD (MCI), 131 I-IMPY was increased in parietal gyrus, temporal gyrus and frontal gyrus compared with normal control group and it were found to be statistically significant (t = 1.3967∼2.8757, all P 0.05). In patients with AD, increase in 131 I-IMPY were observed in parietal, temporal, occipital lobes and basal ganglia compared with normal control group and it were found to be statistically significant (t=2.1001∼6.2789, all P 0.05), and 131 I-IMPY was increased in occipital lobes and basal ganglia compared with MCI group and it were found to be statistically significant (t=2.0850∼3.6772, all P 131 I-IMPY was lightly increased in each brain of left side gyrus compared with right but without statistically significant difference (t=0.1273∼0.5571, all P>0.05). Conclusions: 131 I-IMPY SPECT Imaging was helpful for early diagnosis of AD. (authors)

  19. Chitosan-coated nickel-ferrite nanoparticles as contrast agents in magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Tanveer [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Department of Physics, Abdul Wali Khan University, Mardan (Pakistan); Bae, Hongsub; Iqbal, Yousaf [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Rhee, Ilsu, E-mail: ilrhee@knu.ac.kr [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Hong, Sungwook [Division of Science Education, Daegu University, Gyeongsan 712-714 (Korea, Republic of); Chang, Yongmin; Lee, Jaejun [Department of Diagnostic Radiology, College of Medicine, Kyungpook National University and Hospital, Daegu 700-721 (Korea, Republic of); Sohn, Derac [Department of Physics, Hannam University, Daejon (Korea, Republic of)

    2015-05-01

    We report evidence for the possible application of chitosan-coated nickel-ferrite (NiFe{sub 2}O{sub 4}) nanoparticles as both T{sub 1} and T{sub 2} contrast agents in magnetic resonance imaging (MRI). The coating of nickel-ferrite nanoparticles with chitosan was performed simultaneously with the synthesis of the nickel-ferrite nanoparticles by a chemical co-precipitation method. The coated nanoparticles were cylindrical in shape with an average length of 17 nm and an average width of 4.4 nm. The bonding of chitosan onto the ferrite nanoparticles was confirmed by Fourier transform infrared spectroscopy. The T{sub 1} and T{sub 2} relaxivities were 0.858±0.04 and 1.71±0.03 mM{sup −1} s{sup −1}, respectively. In animal experimentation, both a 25% signal enhancement in the T{sub 1}-weighted mage and a 71% signal loss in the T{sub 2}-weighted image were observed. This demonstrated that chitosan-coated nickel-ferrite nanoparticles are suitable as both T{sub 1} and T{sub 2} contrast agents in MRI. We note that the applicability of our nanoparticles as both T{sub 1} and T{sub 2} contrast agents is due to their cylindrical shape, which gives rise to both inner and outer sphere processes of nanoparticles. - Highlights: • Chitosan-coated nickel-ferrite (Ni-Fe{sub 2}O{sub 4}) nanoparticles were synthesized in an aqueous system by chemical co-precipitation. • The characterization of bare and chitosan-coated nanoparticles were performed using various analytical tools, such as TEM, FTIR, XRD, and VMS. • We evaluated the coated particles as potential T{sub 1} and T{sub 2} contrast agents for MRI by measuring T{sub 1} and T{sub 2} relaxation times as a function of iron concentration. • Both T{sub 1} and T{sub 2} effects were also observed in animal experimentation.

  20. Biocompatible KMnF3 nanoparticular contrast agent with proper plasma retention time for in vivo magnetic resonance imaging.

    Science.gov (United States)

    Liu, Zhi-jun; Song, Xiao-xia; Xu, Xian-zhu; Tang, Qun

    2014-04-18

    Nanoparticular MRI contrast agents are rapidly becoming suitable for use in clinical diagnosis. An ideal nanoparticular contrast agent should be endowed with high relaxivity, biocompatibility, proper plasma retention time, and tissue-specific or tumor-targeting imaging. Herein we introduce PEGylated KMnF3 nanoparticles as a new type of T1 contrast agent. Studies showed that the nanoparticular contrast agent revealed high bio-stability with bovine serum albumin in PBS buffer solution, and presented excellent biocompatibility (low cytotoxicity, undetectable hemolysis and hemagglutination). Meanwhile the new contrast agent possessed proper plasma retention time (circulation half-life t1/2 is approximately 2 h) in the body of the administrated mice. It can be delivered into brain vessels and maintained there for hours, and is mostly cleared from the body within 48 h, as demonstrated by time-resolved MRI and Mn-biodistribution analysis. Those distinguishing features make it suitable to obtain contrast-enhanced brain magnetic resonance angiography. Moreover, through the process of passive targeting delivery, the T1 contrast agent clearly illuminates a brain tumor (glioma) with high contrast image and defined shape. This study demonstrates that PEGylated KMnF3 nanoparticles represent a promising biocompatible vascular contrast agent for magnetic resonance angiography and can potentially be further developed into an active targeted tumor MRI contrast agent.

  1. Advances in technetium chemistry towards 99mTc receptor imaging agents

    International Nuclear Information System (INIS)

    Johannsen, B.; Spies, H.

    1997-01-01

    The development of the chemistry of technetium and its non-radioactive surrogate rhenium has been prompted by the trends and needs of nuclear medicine, which predominantly uses 99m Tc radiopharmaceuticals for a broad range of diagnostics. Technetium-99m is the ideal radioisotope for tomographic single-photon emission tomography (SPECT) imaging due to its nuclear properties (6.2 h, E γ 140 keV) and ready availability through generator systems. Transition metals offer many opportunities for designing molecules by modifying the environment around the core, allowing certain biological properties to be imposed upon the molecule. Whereas research in the past was mainly concerned with biological properties that allow relatively unspecific functional imaging, as in brain or myocardium perfusion studies, nuclear medicine is now requiring more and more biochemical information on low capacity, high specificity targets. Many research groups have become involved in the search for new technetium-based compounds, called the third generation of 99m Tc radiopharmaceuticals, that employ the principles of modern pharmacology to achieve biochemical specificity. There has been considerable interest in imaging CNS and other receptors with 99m Tc receptor-binding ligands. Such a 99m Tc CNS receptor-imaging agent is currently not yet in use because of the significant hurdles to be overcome in attaining this ambitious goal. However, some Tc and Re complexes of remarkable affinity in vitro, and the first high-affinity 99m Tc probes able to label the dopamine transporter in the brain by SPECT imaging prove the feasibility of this approach. (Author)

  2. A pancreas imaging agent-131I-HIPDM: the animal experiment and preliminary clinical application

    International Nuclear Information System (INIS)

    Shao Hesheng

    1988-01-01

    131 I-HIPDM has been used clinically for studying regional cerebral perfusion. The [ 131 I] HIPDM was prepared in a kit. The labelling yields were consistently more than 95%, as analyzed by the TLC-Silica gel. The labelled compound is stable in vitro and in vivo. S D Strain rats (170-220 g) and mice (18-22 g) were used. The pancreatic uptake of [ 131 I] HIPDM is rather slow in mice and rats. At 8 hr after iv, the pancreas activity and the pancreas to liver (P/L) ratio are highest in mice and rats. The effect of carrier loading dose from 0.010 to 6.0 mg/kg on blodistribution in mice has been studied. The liver uptake was increased by adding carrier HIPDM. The result indicates that administration between 0.010 and 0.05 mg/kg carrier dose is most suitable for the pancreas imaging. Gamma camera imaging of dog at 6 hr after iv with 300 μCi [ 131 I] HIPMD, 0.05 mg/kg body weight showed clear pancreas image. The P/L ratio of the dog is 0.40. Preliminary clinical tests were satisfactory. Using 1 to 1.5 mCi of [ 131 I] HIPDM, 0.05 mg/kg, the pancreas imaging was operated in 4 cases of volunteers and pancreas cyst respectively with the good diagnostic quality. The authors are of the opinion that this pancreas imaging agent may have potential value for routine use

  3. Short-lived cyclotron produced radionuclides evaluation on the myocardial imaging agents

    International Nuclear Information System (INIS)

    Rikitake, Tomoyuki; Tateno, Yukio; Yamane, Akiko; Matsumoto, Touru; Umegaki, Youichiro

    1978-01-01

    Organ uptake after venous administration of 13 N-ammonia, 43 K, 86 Rb, 201 Tl and after rectal administration of 13 N-ammonia was studied. Each nuclides highly accumulated in myocardium after intravenous injection, but rectal administrated 13 N-ammonia did not show this tendency. Intravenously injected 13 N-ammonia showed very early myocardial uptake and early secretion from kidney. Rectal administrated 13 N-ammonia was less accumulated in myocardium. 43 KCl and 13 NH 4 Cl were injected intravenously and administrated from the rectum to the rabbits under imaging scintilator system. Whole-body scintiscanner with display-processing unit was used for a 43 KCl injected rabbit. A positroncamera with computer system (TOSBAC 3400 on line system) was used for 13 NH 4 Cl (i.v. and rectal ad.) rabbits. The dynamic studies of 43 KCl, 13 NH 4 Cl were made from these imaging data. The countratio of heart to the liver after 43 K injection was nearly equal or less than the liver. The peakcount was at 15 min after 13 NH 4 Cl intravenous injection. 13 N accumulated promptly at upper mediastinal part and kidney, and soon disappeared from these part. Uptake of the heat was high and that of the liver was low. When 13 NH 4 Cl was administrated from the rectum, 13 N trapped at the liver, and uptake of the heart was very low level. Scintiscanning after 13 KCl intravenously injected, did not show the high resolution. Rabbit heart was distinguishable from the liver, but there are no visibility of the detail. Seeing positronscintigram after 13 NH 4 Cl administration both from intravenously and from rectum, the detail was well visible. We concluded the positron scintigram after 13 NH 4 Cl injection should be a good myocardial imaging agent. Furthermore, 13 Nh 4 Cl has two eminent characters as a myocardial imaging agent comparing 201 TlCl. One is prompt making of image, the others is the very low radiation dose. (auth.)

  4. Residualization Rates of Near-Infrared Dyes for the Rational Design of Molecular Imaging Agents.

    Science.gov (United States)

    Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M

    2015-12-01

    Near-infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, boron-dipyrromethene (BODIPY), and oxazine/thiazine/carbopyronin). We identify residualizing (half-life >24 h) and non-residualizing (half-life <24 h) dyes in both the far-red (~650-680 nm) and near-infrared (~740-800 nm) regions. This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design.

  5. Image Cytometric Analysis of Algal Spores for Evaluation of Antifouling Activities of Biocidal Agents.

    Science.gov (United States)

    Il Koo, Bon; Lee, Yun-Soo; Seo, Mintae; Seok Choi, Hyung; Leng Seah, Geok; Nam, Taegu; Nam, Yoon Sung

    2017-07-31

    Chemical biocides have been widely used as marine antifouling agents, but their environmental toxicity impose regulatory restriction on their use. Although various surrogate antifouling biocides have been introduced, their comparative effectiveness has not been well investigated partly due to the difficulty of quantitative evaluation of their antifouling activity. Here we report an image cytometric method to quantitatively analyze the antifouling activities of seven commercial biocides using Ulva prolifera as a target organism, which is known to be a dominant marine species causing soft fouling. The number of spores settled on a substrate is determined through image analysis using the intrinsic fluorescence of chlorophylls in the spores. Pre-determined sets of size and shape of spores allow for the precise determination of the number of settled spores. The effects of biocide concentration and combination of different biocides on the spore settlement are examined. No significant morphological changes of Ulva spores are observed, but the amount of adhesive pad materials is appreciably decreased in the presence of biocides. It is revealed that the growth rate of Ulva is not directly correlated with the antifouling activities against the settlement of Ulva spores. This work suggests that image cytometric analysis is a very convenient, fast-processable method to directly analyze the antifouling effects of biocides and coating materials.

  6. Contrast agent based on nano-emulsion for targeted biomedical imaging

    International Nuclear Information System (INIS)

    Attia, Mohamed

    2016-01-01

    X-ray imaging agents are essential in combination with X-ray computed tomography to improve contrast enhancement aiming at providing complete visualization of blood vessels and giving structural and functional information on lesions allowing the detection of a tumor. As well as it is fundamental tool to discriminate between healthy cells and pathogens. We successfully limit the problems presented in commercial X-ray contrast agents like poor contrasting in Fenestra VC associated with short blood circulation time and to avoid rapid renal elimination from the body as found in Xenetix (Iobitriol). We developed nontoxic and blood pool iodine-containing nano-emulsion contrast agents serving in preclinical X-ray μ-CT imaging such as, a- Tocopherol (vitamin E), Cholecalciferol (vitamin D3), Castor oil, Capmul MCMC8 oil and oleic acid. Those formulated nano emulsions were prepared by low energy spontaneous emulsification technic with slight modification for each platform. They showed new specific features rendering them promising agents in in vivo experiments as improving the balance between the efficacy and the toxicity of targeted therapeutic interventions. We investigate the effect of size and the chemical composition of the nanoparticles on their biodistribution, pharmacokinetics and toxicity. They demonstrated that the chemical structures of the droplet's cores have significant role in targeting for example vitamin E was mainly accumulated in liver and castor oil formulation was passively accumulated in spleen explaining the proof-of-concept of EPR effect. On the other hand, two different platform sizes of Cholecalciferol molecule revealing that no real impact on the pharmacokinetics and biodistribution but presented remarkable effect on the toxicity. Of particular interest is studying the effect of the surface charge of nanoparticles on their biodistribution, this is why oleic acid nano-emulsion was selected to proceed this study by presence of amphiphilic polymer

  7. A Proposed Computed Tomography Contrast Agent Using Carboxybetaine Zwitterionic Tantalum Oxide Nanoparticles: Imaging, Biological, and Physicochemical Performance.

    Science.gov (United States)

    FitzGerald, Paul F; Butts, Matthew D; Roberts, Jeannette C; Colborn, Robert E; Torres, Andrew S; Lee, Brian D; Yeh, Benjamin M; Bonitatibus, Peter J

    2016-12-01

    The aim of this study was to produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ)-coated soluble tantalum oxide (TaO) nanoparticles (NPs). We chose tantalum to provide superior imaging performance compared with current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. In addition, the aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared with clinically used iodinated agents. We evaluated CT imaging performance of our CZ-TaO NPs compared with that of an iodinated agent in live rats, imaged centrally located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats' great vessels at high temporal resolution during and after contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. Carboxybetaine zwitterionic TaO NPs were synthesized and analyzed in detail. We used multidimensional nuclear magnetic resonance to determine surface functionality of the NPs. We measured NP size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations

  8. Preparation of 99mTc-Ancitabine as a Possible Tumor Imaging Agent

    International Nuclear Information System (INIS)

    Ibrahim, I.T.; Attallah, K.M.

    2010-01-01

    Ancitabine is one of the potent chemotherapeutic anticancer drugs. Tc-Ancitabine ( 99m Tc-ANC) was prepared using stannous chloride as reducing agent, which produced yield above 90% at ph 4 at room temperature within 1-5 min as reaction time. The labeled drug was stable for more than 8 h post labeling. Biodistribution study of 99m Tc-ANC in normal mice reflected that its uptake was increased in organ of high proliferation like stomach. In solid tumor bearing mice 99m Tc-ANC was incorporated rapidly in tumor site and declined slowly, while it was declined rapidly from other tissues. Biodistribution of 99m Tc-ANC in solid tumor presented a possible model for imaging of tumors.

  9. Potential new approaches for the development of brain imaging agents for single-photon applications

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.; Srivastava, P.C.

    1984-01-01

    This paper describes new strategies for the brain-specific delivery of radionuclides that can be used to evaluate regional cerebral perfusion by single photon imaging techniques. A description of several examples of interesting new strategies that have recently been reported is presented. A new approach at this institution for the brain-specific delivery of radioiodinated iodophenylalkyl-substituted dihyronicotinamide systems is described which shows good brain uptake and retention in preliminary studies in rats. Following transport into the brain these agents appear to undergo facile intracerebral oxidation to the quaternized analogues which do not recross the intact blood-brain barrier and so are effectively trapped in the brain. 49 refs., 9 figs., 1 tab

  10. Technetium-99m-dimethylglyoxime ([sup 99m]Tc-DMG) as renal imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Adonaylo, V.N. (Buenos Aires Univ. (Argentina). Facultad de Ciencias Exactas y Naturales Buenos Aires Univ. (Argentina). Dept. de Ciencias Biologicas); Stahl, Adriana; Pomilio, A.B.; Vitale, A.A. (Buenos Aires Univ. (Argentina). Facultad de Ciencias Exactas y Naturales); Canellas, C.O. (Buenos Aires Univ. (Argentina). Facultad de Ciencias Exactas y Naturales Comision Nacional de Energia Atomica, Buenos Aires (Argentina))

    1993-06-01

    Dimethylglyoxime (DMG) labelled with [sup 99m]Tc is presented as a renal imaging agent. The behaviour of this complex was analysed at different pH by means of UV spectral data and using DMG-calcium chloride as a reference complex. Biokinetic data were evaluated in two biological models, Sprague-Dawley rats and Didelphis albiventris argentine opossum. Biodistribution in rats demonstrated fast and specific renal excretion. Time-activity values over both kidneys could be quantified for this complex. Renographic studies led to mean time-to maximum values on twelve assays of 2.0 [+-] 0.1 min and a mean relative function of 53.0 [+-] 2.3 and 47.0 [+-] 3.2 for right and left kidneys, respectively. [sup 99m]Tc-DMG showed specificity for the renal excretion pathway and therefore seems to be a very useful radiopharmaceutical for renal function studies. (Author).

  11. Radiation dosimetry of iodine-123 HEAT, an alpha-1 receptor imaging agent

    International Nuclear Information System (INIS)

    Thomas, K.D.; Greer, D.M.; Couch, M.W.; Williams, C.M.

    1987-01-01

    Biologic distribution data in the rat were obtained for the alpha-1 adrenoceptor imaging agent (+/-) 2-[beta-(iodo-4-hydroxyphenyl)ethylaminomethyl]tetralone (HEAT) labeled with [ 123 I]. The major excretory routes were through the liver (67%) and the kidney (33%). Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads, and red bone marrow were calculated for the human using the physical decay data for [ 123 I]. The critical organ was found to be the lower large intestine, receiving 1.1 rad per mCi of [ 123 I]HEAT administered. The total-body dose was found to be 58 mrad per mCi

  12. Synthesis and evaluation of p-iodo-phentermine (IP) as a brain perfusion imaging agent

    International Nuclear Information System (INIS)

    Kizuka, H.; Elmaleh, D.R.; Brownell, G.L.; Strauss, H.W.

    1985-01-01

    rho-( 123 I and 131 I) iodo α,α-dimethylphenethylamine (rho-iodophentermine, IP) as the α-methylated analogue of iodoamphetamine has been prepared. It is hoped that this methyl substitution will increase the lipophilicity of the agent, enhance resistance to metabolism by monoamine oxidase, and will result in increased initial uptake and slower washout from the brain as compared to N-isopropyl-rho-( 123 I) iodoamphetamine. IP was prepared by diazotization of rho-aminophentermine followed by decomposition of the diazonium salt with KI. Radioiodinated IP was prepared either by the solid-phase isotopic exchange reaction or by decomposition of the piperidinotriazene derivative with a radiochemical yield of 40-60%. Biodistribution of 131 I-IP in rats showed brain uptake in the range of 1.7% dose g -1 at 5, 30 and 60 min. Imaging studies with 123 I-IP in dogs showed high brain extraction and slow washout of activity. (author)

  13. Synthesis and 131I labelling of epidepride as a dopamine D2 receptor imaging agent

    International Nuclear Information System (INIS)

    Yang Min; Hu Mingyang; Pei Zhuguo; Wang Bocheng; Zhou Xingqin

    2001-01-01

    S-(-)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2, 3-dimethoxybenzamide (Epidepride) and its iodine labeling precursor S-(-)-N-[(1-Ethyl-2-pyrrolidinyl)methyl]-5-tributyltin-2, 3-dimethoxybenzamide are synthesized from 3-methoxy salicylic acid. The labeling precursor is labeled with 131 I by hydrogen peroxide method, and 131 I-epidepride is gained, its radiolabelling yield (RLY) and the radiochemical purity (RCP) are all over 95%. The RCP of 131 I-epidepride is over 90% under 4 degree C after 15 days. 131 I-epidepride has high affinity to dopamine D 2 receptor. The striatal uptake can be blocked completely by spiperone. The striatum and cerebellum uptake ratio can reach 237 at 320 min in rats. The results show that 131 I-epidepride may be used as a dopamine D 2 receptor imaging agent for SPECT

  14. On-bead combinatorial synthesis and imaging of chemical exchange saturation transfer magnetic resonance imaging agents to identify factors that influence water exchange.

    Science.gov (United States)

    Napolitano, Roberta; Soesbe, Todd C; De León-Rodríguez, Luis M; Sherry, A Dean; Udugamasooriya, D Gomika

    2011-08-24

    The sensitivity of magnetic resonance imaging (MRI) contrast agents is highly dependent on the rate of water exchange between the inner sphere of a paramagnetic ion and bulk water. Normally, identifying a paramagnetic complex that has optimal water exchange kinetics is done by synthesizing and testing one compound at a time. We report here a rapid, economical on-bead combinatorial synthesis of a library of imaging agents. Eighty different 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid (DOTA)-tetraamide peptoid derivatives were prepared on beads using a variety of charged, uncharged but polar, hydrophobic, and variably sized primary amines. A single chemical exchange saturation transfer image of the on-bead library easily distinguished those compounds having the most favorable water exchange kinetics. This combinatorial approach will allow rapid screening of libraries of imaging agents to identify the chemical characteristics of a ligand that yield the most sensitive imaging agents. This technique could be automated and readily adapted to other types of MRI or magnetic resonance/positron emission tomography agents as well.

  15. Radioiodination and Biological Evaluation of Atenolol as a Possible Cardiac Imaging Agent

    International Nuclear Information System (INIS)

    EI-Mouhty, N.A.R.; Attallah, K.M.; EI-Tawoosy, M.; EI-Kolaly, M.T.

    2008-01-01

    An adopted method for the preparation of high radiochemical purity 125 I iodoatenolol (3-1( 125 I]-4-(2-hydroxy-3-isopropyl aminopropoxy) phenylacetamide) was developed in order to characterize the binding properties ofβ 1 -receptors. Direct radioiodination of atenolol (RS)-4-(2-hydroxy-3-isopropyl aminopropoxy) phenylacetamide) was carried out using chloramine- T (N-chloro-p-toluene sulfonamide sodium salt) or iodogen (1,3,4,6-tetrachloro-3α, 6α-diphenyl glycoril) as an oxidizing agent. The reaction proceeds well within 30 min at ambient room temperature up to 25± 1 degree C and afforded a radiochemical yield up to 85 % as pure as ( 125 I] iodoatenolol increased to over 95 % using neutral lyophilized solution of Na 125 I. Different chromatographic techniques (electrophoresis and thin layer chromatography TLC) were used to evaluate the radiochemical yield and purity of thc labeled product. Biodistribution studies were carried out in normal Albino Swiss mice and the results indicate the possibility of using ( 125 1) iodoatenolol as myocardial imaging agent

  16. Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

    Directory of Open Access Journals (Sweden)

    Nagendra Sanyasihally Ningaraj

    2013-05-01

    Full Text Available Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB. Studies in our laboratory have identified significant differences in the expression levels of certain genes and proteins between normal and brain tumor capillary endothelial cells. In this study, we validated the non-invasive and clinically relevant Dynamic Contrast Enhancing-Magnetic Resonance Imaging (DCE-MRI method with invasive, clinically irrelevant but highly accurate Quantitative Autoradiography (QAR method using rat glioma model. We also showed that DCE-MRI metric of tissue vessel perfusion-permeability is sensitive to changes in blood vessel permeability following administration of calcium-activated potassium (BKCa channel activator NS-1619. Our results show that human gliomas and brain tumor endothelial cells that overexpress BKCa channels can be targeted for increased BTB permeability for MRI enhancing agents to brain tumors. We conclude that monitoring the outcome of increased MRI enhancing agents’ delivery to microsatellites and leading tumor edges in glioma patients would lead to beneficial clinical outcome.

  17. EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging.

    Science.gov (United States)

    Longo, Dario Livio; Moustaghfir, Fatima Zzahra; Zerbo, Alexandre; Consolino, Lorena; Anemone, Annasofia; Bracesco, Martina; Aime, Silvio

    2017-06-15

    Chemical Exchange Saturation Transfer (CEST) approach is a novel tool within magnetic resonance imaging (MRI) that allows visualization of molecules possessing exchangeable protons with water. Many molecules, employed as excipients for the formulation of finished drug products, are endowed with hydroxyl, amine or amide protons, thus can be exploitable as MRI-CEST contrast agents. Their high safety profiles allow them to be injected at very high doses. Here we investigated the MRI-CEST properties of several excipients (ascorbic acid, sucrose, N-acetyl-d-glucosamine, meglumine and 2-pyrrolidone) and tested them as tumor-detecting agents in two different murine tumor models (breast and melanoma cancers). All the investigated molecules showed remarkable CEST contrast upon i.v. administration in the range 1-3ppm according to the type of mobile proton groups. A marked increase of CEST contrast was observed in tumor regions up to 30min post injection. The combination of marked tumor contrast enhancement and lack of toxicity make these molecules potential candidates for the diagnosis of tumors within the MRI-CEST approach. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Manganese and Gd-DTPA stearyl liposomes as reticuloendothelial-system-specific MR imaging contrast agents

    International Nuclear Information System (INIS)

    Wuthrich, R.; Schwendener, R.; Duewell, S.; VonSchulthess, G.K.; Fuchs, W.A.

    1988-01-01

    Liposomes can be used to target metal ions as MR contrast agents to liver and spleen. It was the aim of this work to examine unilamellar liposomes containing manganese and gadolinium ions with respect to their targetting ability, contrast enhancement, and in vivo kinetics in rats and dogs. Unilamellar liposomes containing DTPA stearate were complexed with Mn/sup 2+/ and Gd/sup 3+/ resulting in vesicles of 30-40 nm. Injected into rats, approximately 35% of manganese liposomes were present in the liver after 30-60 minutes, and after 24 hours more than 80% had been eliminated. The pharmacokinetics of gadolinium were more protracted. In MR imaging, a reduction in the T1 of the liver parenchyma from 450 to 170 and 280 msec was observed for manganese and gadolinium liposomes (0.03 mmol/kg body weight), respectively, with the liver appearing as bright as fat. Manganese (and Gd-DTPA) stearyl liposomes are potential organ-selective contrast agents for liver and spleen and are eliminated through a hepatobiliary route

  19. Quantitative Molecular Imaging with a Single Gd-Based Contrast Agent Reveals Specific Tumor Binding and Retention in Vivo.

    Science.gov (United States)

    Johansen, Mette L; Gao, Ying; Hutnick, Melanie A; Craig, Sonya E L; Pokorski, Jonathan K; Flask, Chris A; Brady-Kalnay, Susann M

    2017-06-06

    Magnetic resonance imaging (MRI) has become an indispensable tool in the diagnosis and treatment of many diseases, especially cancer. However, the poor sensitivity of MRI relative to other imaging modalities, such as PET, has hindered the development and clinical use of molecular MRI contrast agents that could provide vital diagnostic information by specifically locating a molecular target altered in the disease process. This work describes the specific and sustained in vivo binding and retention of a protein tyrosine phosphatase mu (PTPμ)-targeted, molecular magnetic resonance (MR) contrast agent with a single gadolinium (Gd) chelate using a quantitative MRI T 1 mapping technique in glioma xenografts. Quantitative T 1 mapping is an imaging method used to measure the longitudinal relaxation time, the T 1 relaxation time, of protons in a magnetic field after excitation by a radiofrequency pulse. T 1 relaxation times can in turn be used to calculate the concentration of a gadolinium-containing contrast agent in a region of interest, thereby allowing the retention or clearance of an agent to be quantified. In this context, retention is a measure of molecular contrast agent binding. Using conventional peptide chemistry, a PTPμ-targeted peptide was linked to a chelator that had been conjugated to a lysine residue. Following complexation with Gd, this PTPμ-targeted molecular contrast agent containing a single Gd ion showed significant tumor enhancement and a sustained increase in Gd concentration in both heterotopic and orthotopic tumors using dynamic quantitative MRI. This single Gd-containing PTPμ agent was more effective than our previous version with three Gd ions. Differences between nonspecific and specific agents, due to specific tumor binding, can be determined within the first 30 min after agent administration by examining clearance rates. This more facile chemistry, when combined with quantitative MR techniques, allows for widespread adoption by academic

  20. Radioiodine labelled SP-4 as an imaging agent for atherosclerotic plaques

    International Nuclear Information System (INIS)

    Zhang Yongxue; Wu Zhijian; Cao Wei

    2000-01-01

    The clinical prospect of radioiodinated SP-4 as an atherosclerotic plaque imaging agent was studied. The SP-4 was synthesized by a solid phase method and identified by an amino acid analysis after purification with HPLC. SP-4 was labelled with 131 I and 125 I by the Chloramine-T method and purified through Sephadex G-25 column. Twelve New Zealand rabbits were divided into an atherosclerotic group (n = 7, AR) and a control group (n = 5, NR). All of the atherosclerotic rabbits were intravenous administrated with bovine serum albumin, then feb with high cholesterol and fat diet. 125 I-SP-4 was intravenous administrated to the rabbits of both groups. The biodistribution of 125 I-SP-4 in rabbits was investigated. The uptakes (% ID/g) in blood and thoracic aorta and abdominal aorta were calculated 4 hours postinjection. Macro-autoradiography and micro-autoradiography were performed in 2 AR atherosclerotic abdominal aortas. The clearance of radioactivity from plasma was very rapid. 125 I-SP-4 was mainly excreted through kidneys. The radioactive uptakes of abdominal aorta and thoracic aorta of AR at 4 hours postinjection were significantly higher than that of NR. The films of macro-autoradiography showed focal accumulation of the radioactivity in the areas of a newly formed edges of atherosclerotic plaques. On the slices of micro-autoradiography, the obvious radioactive accumulation could be found in the atherosclerotic plaques. Thus it was seen that the SP-4 remained its biological activity after radioiodination and was located at atherosclerotic lesions, it is potentially useful as an atherosclerotic plaque imaging agent

  1. Study of biodistribution properties of a new myocardial imaging agent 99Tcm-N-DBODC5

    International Nuclear Information System (INIS)

    Zhang Wanchun; Fang Wei; Wang Feng; Guo Feng; Guo Lin; He Zuoxiang; Wang Xuebin; Lin Bin; Tang Zhigang

    2007-01-01

    99 Tc m -N-DBODC5 for intravenous injection was prepared. The labelling yield was 95.0% ± 0.52%. Sixteen New Zealand rabbits were involved and planar gamma imaging was performed at 10 time-point after injection of 99 Tc m -N-DBODC5. The radioactivity changes of organs were calculated by regions of interest (ROI) analysis. The 16 rabbits were divided into 4 groups and were sacrificed at 30, 60, 120, and 180 min after iniection respectively. The activity for all excised organs were measured by γ-well counting for calculating radiouptake. Myocardial uptake for 99 Tc m -N-DBODC5 is high. Though myocardial uptake was lower than 99 Tc m -MIBI, the liver clearance for 99 Tc m -N-DBODC5 was more rapid than that of 99 Tc m MIBI. As early as 30 min after injection, 99 Tc m -N-DBODC5 heart-to-liver ratio is 0.98 ± 0.52 versus 0.56 ± 0.19 for 99 Tc m -MIBI (P 99 Tc m -N-DBODC5 heart-to-liver ratio improved to the peak value (1.18 ± 0.57), compared with 0.71 ± 0.29 for 99 Tc m -MIBI, P 99 Tc m - N-DBODC5 was keeping at a high level until 180 min. 99 Tc m -N-DBODC5 exhibited rapid lung clearance, similar to that of 99 Tc m -MIBI. The biodistribution in the isolated organs demonstrated the same trend. The rapid 99 Tc m -N-DBODC5 liver clearance may allow the earlier imaging, and overcome the photon scatter from the liver with high activity which interfered the inferoapical wall in myocardial images. 99 Tc m -N-DBODC5 is a promising new myocardial perfusion imaging agent with superior biodistribution properties. (authors)

  2. Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.

    Science.gov (United States)

    Parrish-Novak, Julia; Byrnes-Blake, Kelly; Lalayeva, Narine; Burleson, Stefanie; Fidel, Janean; Gilmore, Rhonda; Gayheart-Walsten, Pamela; Bricker, Gregory A; Crumb, William J; Tarlo, K S; Hansen, Stacey; Wiss, Valorie; Malta, Errol; Dernell, William S; Olson, James M; Miller, Dennis M

    BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials.

  3. pH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent

    Science.gov (United States)

    Wu, Yunkou; Zhang, Shanrong; Soesbe, Todd C.; Yu, Jing; Vinogradov, Elena; Lenkinski, Robert E.; Sherry, A. Dean

    2015-01-01

    Purpose This study explored the feasibility of using a pH responsive paraCEST agent to image the pH gradient in kidneys of healthy mice. Methods CEST signals were acquired on an Agilent 9.4 T small animal MRI system using a steady-state gradient echo pulse sequence after a bolus injection of agent. The magnetic field inhomogeneity across each kidney was corrected using the WASSR method and pH maps were calculated by measuring the frequency of water exchange signal arising from the agent. Results Dynamic CEST studies demonstrated that the agent was readily detectable in kidneys only between 4 to 12 min post-injection. The CEST images showed a higher signal intensity in the pelvis and calyx regions and lower signal intensity in the medulla and cortex regions. The pH maps reflected tissue pH values spanning from 6.0 to 7.5 in kidneys of healthy mice. Conclusion This study demonstrated that pH maps of the kidney can be imaged in vivo by measuring the pH-dependent chemical shift of a single water exchange CEST peak without prior knowledge of the agent concentration in vivo. The results demonstrate the potential of using a simple frequency-dependent paraCEST agent for mapping tissue pH in vivo. PMID:26173637

  4. Hypoxic-ischemic encefalopathy: Clinical course and prognosis

    Directory of Open Access Journals (Sweden)

    Ćosić-Cerovac Nataša

    2003-01-01

    Full Text Available Background. Establishing the value of neurological examination, and additional diagnostic methods (ultrasonography and magnetic resonance imaging of the brain in the diagnosis and prognosis of hypoxic-ischemic encephalopathy and its treatment, tracking the clinical course, and making the prognosis of neurological development in newborn infants with hypoxic-ischemic encefalopathy. Methods. The group of 40 term newborn infants with suspected intrauterine asphyxia was examined. All the infants were prospectivelly followed untill the 3rd year of age at the Clinic for Neurology and Psychiatry for Children and Youth in order to estimate their neurological development and to diagnose the occurence of persistent neurological disorders. All the infants were analyzed by their gestational age and Apgar score in the 1st and the 5th minute of life. They were all examined neurologically and by ultrasonography in the first week of life and, repeatedly, at the age of 1, 3, 6, 9, 12, 18, as well as in the 24th month of life. They were treated by the standard methods for this disease. Finally, all the infants were examined neurologically and by magnetic resonance imaging of the brain in their 3rd year of age. On the basis of neurological finding infants were devided into 3 groups: infants with normal neurological finding, infants with mild neurological symptomatology, and infants with severe neurological disorders. Results. It was shown that neurological finding, ultrasonography and magnetic resonance imaging of the brain positively correlated with the later neurological development of the infants with hypoxic-ischemic encephalopathy. Conclusion. Only the combined use of these techniques had full diagnostic and prognostic significance emphasizing that the integrative approach was very important in the diagnosis of brain lesions in infants.

  5. Synthesis Of Gd-dtpa-folat For Magnetic Resonance Imaging Contrast Agent And Characterization By Using 153gd-dtpa-folate Radioactive

    OpenAIRE

    G., Adang H; S., Yono; Maskur

    2012-01-01

    Contrast agent was used to clarify the image of the organ that is difficult to distinguish by MRI (Magnetic Resonance Imaging) techniques, particularly in soft tissues of the central nervous system, liver, digestive system, lymphatic system, breast, cardiovascular and pulmonary systems. One of the commonly used contrast agents in hospitals is Gadolinium-DieThylenetriamine Pentaacetic Acid (Gd-DTPA). Gd-DTPA is non specific contrast agent, therefore it has led to develop a contrast agent that ...

  6. A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging.

    Science.gov (United States)

    Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

    2016-04-01

    The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Simple method for quantification of gadolinium magnetic resonance imaging contrast agents using ESR spectroscopy.

    Science.gov (United States)

    Takeshita, Keizo; Kinoshita, Shota; Okazaki, Shoko

    2012-01-01

    To develop an estimation method of gadolinium magnetic resonance imaging (MRI) contrast agents, the effect of concentration of Gd compounds on the ESR spectrum of nitroxyl radical was examined. A solution of either 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPONE) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) was mixed with a solution of Gd compound and the ESR spectrum was recorded. Increased concentration of gadolinium-diethylenetriamine pentaacetic acid chelate (Gd-DTPA), an MRI contrast agent, increased the peak-to-peak line widths of ESR spectra of the nitroxyl radicals, in accordance with a decrease of their signal heights. A linear relationship was observed between concentration of Gd-DTPA and line width of ESR signal, up to approximately 50 mmol/L Gd-DTPA, with a high correlation coefficient. Response of TEMPONE was 1.4-times higher than that of TEMPOL as evaluated from the slopes of the lines. The response was slightly different among Gd compounds; the slopes of calibration curves for acua[N,N-bis[2-[(carboxymethyl)[(methylcarbamoyl)methyl]amino]ethyl]glycinato(3-)]gadolinium hydrate (Gd-DTPA-BMA) (6.22 μT·L/mmol) and gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelate (Gd-DOTA) (6.62 μT·L/mmol) were steeper than the slope for Gd-DTPA (5.45 μT·L/mmol), whereas the slope for gadolinium chloride (4.94 μT·L/mmol) was less steep than that for Gd-DTPA. This method is simple to apply. The results indicate that this method is useful for rough estimation of the concentration of Gd contrast agents if calibration is carried out with each standard compound. It was also found that the plot of the reciprocal square root of signal height against concentrations of contrast agents could be useful for the estimation if a constant volume of sample solution is taken and measured at the same position in the ESR cavity every time.

  8. Biological evaluation of 99mTC cis-Pt iminoacetic acid complexes as tumour imaging agents

    International Nuclear Information System (INIS)

    Awaluddin, A.; Jacobs, J.J.; Bourne, D.W.; Maddalena, D.J.; Wilson, J.G.; Boyd, D.W.

    1987-01-01

    The biodistributions of three new 99m Tc labelled cis-platinum bifunctional tumour imaging agents were examined in mice bearing a certain type of sarcoma between 15 minutes and 24 hours post injection. The three complexes were excreted primarily via the renal pathway into the urine but at quite different rates. All complexes had some affinity for the tumour, but complexes III had the greatest, with tumour to blood and tumour to muscle rates at 24 hours in excess of 10:1 and 18:1. Biodistribution results were calculated using Tiscon Program. Suggesting that the three complexes may be useful as tumour imaging agents. (M.E.L.) [es

  9. New radioiodinated carboxylic and hydroxamic matrix metalloproteinase inhibitor tracers as potential tumor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Oltenfreiter, Ruth E-mail: ruth.oltenfreiter@rug.ac.be; Staelens, Ludovicus; Lejeune, Annabelle; Dumont, Filip; Frankenne, Francis; Foidart, Jean-Michel; Slegers, Guido

    2004-05-01

    Several studies have demonstrated a positive correlation between tumor progression and expression of extracellular proteinases such as matrix metalloproteinases (MMPs). MMP-2 and MMP-9 have become attractive targets for cancer research because of their increased expression in human malignant tumor tissues of various organs, providing a target for medical imaging techniques. Radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4'-[{sup 123}I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid (9) and 2-(4'-[{sup 123}I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionamide (11) were synthesized by electrophilic aromatic substitution of the tributylstannyl derivatives and resulted in radiochemical yields of 60% {+-} 5% (n = 3) and 70% {+-} 5% (n = 6), respectively. In vitro zymography and enzyme assays showed high inhibition capacities of the inhibitors on gelatinases. In vivo biodistribution showed no long-term accumulation in organs and the possibility to accumulate in the tumor. These results warrant further studies of radioiodinated carboxylic and hydroxamic MMP inhibitor tracers as potential SPECT tumor imaging agents.

  10. New radioiodinated carboxylic and hydroxamic matrix metalloproteinase inhibitor tracers as potential tumor imaging agents

    International Nuclear Information System (INIS)

    Oltenfreiter, Ruth; Staelens, Ludovicus; Lejeune, Annabelle; Dumont, Filip; Frankenne, Francis; Foidart, Jean-Michel; Slegers, Guido

    2004-01-01

    Several studies have demonstrated a positive correlation between tumor progression and expression of extracellular proteinases such as matrix metalloproteinases (MMPs). MMP-2 and MMP-9 have become attractive targets for cancer research because of their increased expression in human malignant tumor tissues of various organs, providing a target for medical imaging techniques. Radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4'-[ 123 I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid (9) and 2-(4'-[ 123 I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionamide (11) were synthesized by electrophilic aromatic substitution of the tributylstannyl derivatives and resulted in radiochemical yields of 60% ± 5% (n = 3) and 70% ± 5% (n = 6), respectively. In vitro zymography and enzyme assays showed high inhibition capacities of the inhibitors on gelatinases. In vivo biodistribution showed no long-term accumulation in organs and the possibility to accumulate in the tumor. These results warrant further studies of radioiodinated carboxylic and hydroxamic MMP inhibitor tracers as potential SPECT tumor imaging agents

  11. Self-Assembled Polyelectrolyte Nanoparticles as Fluorophore-Free Contrast Agents for Multicolor Optical Imaging

    Directory of Open Access Journals (Sweden)

    Da Hye Shin

    2015-03-01

    Full Text Available In this work, we describe the fabrication of self-assembled polyelectrolyte nanoparticles that provide a multicolor optical imaging modality. Poly(γ-glutamic acid(γ-PGA formed self-assembled nanoparticles through electrostatic interactions with two different cationic polymers: poly(L-lysine(PLL and chitosan. The self-assembled γ-PGA/PLL and γ-PGA/chitosan nanoparticles were crosslinked by glutaraldehyde. Crosslinking of the ionic self-assembled nanoparticles with glutaraldehyde not only stabilized the nanoparticles but also generated a strong autofluorescence signal. Fluorescent Schiff base bonds (C=N and double bonds (C=C were generated simultaneously by crosslinking of the amine moiety of the cationic polyelectrolytes with monomeric glutaraldehyde or with polymeric glutaraldehyde. The unique optical properties of the nanoparticles that resulted from the crosslinking by glutaraldehyde were analyzed using UV/Vis and fluorescence spectroscopy. We observed that the fluorescence intensity of the nanoparticles could be regulated by adjusting the crosslinker concentration and the reaction time. The nanoparticles also exhibited high performance in the labeling and monitoring of therapeutic immune cells (macrophages and dendritic cells. These self-assembled nanoparticles are expected to be a promising multicolor optical imaging contrast agent for the labeling, detection, and monitoring of cells.

  12. Technetium-99m dextran: a promising new protein-losing enteropathy imaging agent

    International Nuclear Information System (INIS)

    Bhatnagar, A.; Singh, A.K.; Lahoti, D.; Singh, T.; Khanna, C.M.

    1996-01-01

    The purpose of this study was to evaluate technetium-99m dextran ( 99m Tc-Dx; molecular weight 81000) as a prospective protein-losing enteropathy (PLE) imaging agent. Twenty-two patients iwth diseases commonly associated with PLE and 12 healthy control subjects underwent intravenous 99m Tc-Dx scintigraphy. All of the 22 test patients showed significant radiotracer accumulation in the intestines within 3-4 h post injection. The focal, regional or generalised nature of the enteropathy and involvement of the large or small intestine could be identified in most cases. Four of the 12 apparently healthy subjects also showed minimal accumulation in the abdominal area occurring late in the study period. This could have been physiological, related to food habits or due to unsuspected intestinal worms. We attribute the high sensitivity of 99m Tc-Dx to its relatively fast blood (background) clearance. The radiotracer may have several other advantages over 99m Tc-labelled human serum albumin in imaging PLE. (orig.)

  13. Plasmon-resonant nanorods as multimodal agents for two-photon luminescent imaging and photothermal therapy

    Science.gov (United States)

    Huff, Terry B.; Hansen, Matthew N.; Tong, Ling; Zhao, Yan; Wang, Haifeng; Zweifel, Daniel A.; Cheng, Ji-Xin; Wei, Alexander

    2007-02-01

    Plasmon-resonant gold nanorods have outstanding potential as multifunctional agents for image-guided therapies. Nanorods have large absorption cross sections at near-infrared (NIR) frequencies, and produce two-photon luminescence (TPL) when excited by fs-pulsed laser irradiation. The TPL signals can be detected with single-particle sensitivity, enabling nanorods to be imaged in vivo while passing through blood vessels at subpicomolar concentrations. Furthermore, cells labeled with nanorods become highly susceptible to photothermal damage when irradiated at plasmon resonance, often resulting in a dramatic blebbing of the cell membrane. However, the straightforward application of gold nanorods for cell-specific labeling is obstructed by the presence of CTAB, a cationic surfactant carried over from nanorod synthesis which also promotes their nonspecific uptake into cells. Careful exchange and replacement of CTAB can be achieved by introducing oligoethyleneglycol (OEG) units capable of chemisorption onto nanorod surfaces by in situ dithiocarbamate formation, a novel method of surface functionalization. Nanorods with a dense coating of methyl-terminated OEG chains are shielded from nonspecific cell uptake, whereas nanorods functionalized with folate-terminated OEG chains accumulate on the surface of tumor cells overexpressing their cognate receptor, with subsequent delivery of photoinduced cell damage at low laser fluence.

  14. Porphyrin-containing polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents.

    Science.gov (United States)

    Yan, Guo-Ping; Li, Zhen; Xu, Wei; Zhou, Cheng-Kai; Yang, Lian; Zhang, Qiao; Li, Liang; Liu, Fan; Han, Lin; Ge, Yuan-Xing; Guo, Jun-Fang

    2011-04-04

    Porphyrin-containing polyaspartamide ligands (APTSPP-PHEA-DTPA) were synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(4'-aminophenyl)-10,15,20-tris(4'-sulfonatophenyl) porphyrin, trisodium salt (APTSPP) into poly-α,β-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA). These ligands were further reacted with gadolinium chloride to produce macromolecule-gadolinium complexes (APTSPP-PHEA-DTPA-Gd). Experimental data of (1)H NMR, IR, UV and elemental analysis evidenced the formation of the polyaspartamide ligands and gadolinium complexes. In vitro and in vivo property tests indicated that APTSPP-PHEA-DTPA-Gd possessed noticeably higher relaxation effectiveness, less toxicity to HeLa cells, and significantly higher enhanced signal intensities (SI) of the VX2 carcinoma in rabbits with lower injection dose requirement than that of Gd-DTPA. Moreover, APTSPP-PHEA-DTPA-Gd was found to greatly enhance the contrast of MR images of the VX2 carcinoma, providing prolonged intravascular duration, and distinguished the VX2 carcinoma and normal tissues in rabbits according to MR image signal enhancements. These porphyrin-containing polyaspartamide gadolinium complexes can be used as the candidates of contrast agents for targeted MRI to tumors. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  15. Turnover rate of hypoxic cells in solid tumors

    International Nuclear Information System (INIS)

    Ljungkvist, A.S.E.; Bussink, J.; Rijken, P.F.J.W.; Van Der Kogel, A.J.

    2003-01-01

    Most solid tumors contain hypoxic cells, and both the amount and duration of tumor hypoxia has been shown to influence the effect of radiation treatment negatively. It is important to understand the dynamic processes within the hypoxic cell population in non-treated tumors, and the effect of different treatment modalities on the kinetics of hypoxic cells to be able to design optimal combined modality treatments. The turnover rate of hypoxic cells was analyzed in three different solid tumor models with a double bio-reductive hypoxic marker assay with sequential injection of the two hypoxic markers. Previously it was shown that this assay could be used to detect both a decrease and an increase of tumor hypoxia in relation to the tumor vasculature with high spatial resolution. In this study the first hypoxic marker, pimonidazole, was administered at variable times relative to tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. The hypoxic cell turnover rate was calculated as the loss of pimonidazole positive cells relative to CCI-103F. The murine C38 line had the fastest hypoxic turnover rate of 60% /24h and the human xenograft line SCCNij3 had the slowest hypoxic turnover rate of 30% /24 h. The hypoxic turnover rate was most heterogeneous in the SCCNij3 line that even contained viable groups of cells that had been hypoxic for at least 5 days. The human xenograft line MEC82 fell in between with a hypoxic turnover rate of 50% /24 h. The hypoxic cell turnover was related to the potential tumor volume doubling time (Tpot) with a Tpot of 26h in C38 and 103h in SCCNij3. The dynamics of hypoxic cells, quantified with a double hypoxic marker method, showed large differences in hypoxic cell turnover rate and were related to Tpot

  16. Preparation and evaluation of 68Ga-ECC as a PET renal imaging agent

    International Nuclear Information System (INIS)

    Mizaei, Alireza; Jaililan, Amir Reza; Mazidi, Mohammad; Aghanejad, Ayuob; Yousefnia, Hassan; Shabani, Gholamli; Ardaneh, Khosro; Geramifar, Patham; Beiki, Davood

    2015-01-01

    Development of a gallium-68-labeled renal tracer can be a good substitute for Tc-99m, a known SPECT tracer. In this study, effort was made to develop 68 Ga-ethylenecysteamine cysteine ( 68 Ga-ECC). Ga-ECC was prepared using generator-based 68 GaCl3 and ethylenecysteamine cysteine (ECC) at optimized conditions. Stability of the complex was checked in human serum followed by partition coefficient determination of the tracer. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 120 min. Ga-ECC was prepared at optimized conditions in 15 min at 90 °C (radiochemical purity ≈97 ± 0.88 % ITLC, >99 % HPLC, specific activity: 210 ± 5 GBq/mM). 68 Ga-ECC was a water-soluble complex based on partition coefficient data (log P; −1.378) and was stable in the presence of human serum for 2 h at 37 °C. The biodistribution of the tracer demonstrated high kidney excretion of the tracer in 10–20 min. The SUV max ratios of the liver to left kidney were 0.38 and 0.39 for 30 and 90 min, respectively, indicating high kidney uptake. Initial biodistribution results showed significant kidney and urinary excretion of the tracer comparable to that of the homologous 99m Tc compound. The complex could be a possible PET kidney imaging agent with a fast imaging time

  17. Preparation and evaluation of {sup 68}Ga-ECC as a PET renal imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Mizaei, Alireza; Jaililan, Amir Reza; Mazidi, Mohammad; Aghanejad, Ayuob; Yousefnia, Hassan; Shabani, Gholamli; Ardaneh, Khosro [Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of); Geramifar, Patham; Beiki, Davood [Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2015-09-15

    Development of a gallium-68-labeled renal tracer can be a good substitute for Tc-99m, a known SPECT tracer. In this study, effort was made to develop {sup 68}Ga-ethylenecysteamine cysteine ({sup 68}Ga-ECC). Ga-ECC was prepared using generator-based {sup 68}GaCl3 and ethylenecysteamine cysteine (ECC) at optimized conditions. Stability of the complex was checked in human serum followed by partition coefficient determination of the tracer. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 120 min. Ga-ECC was prepared at optimized conditions in 15 min at 90 °C (radiochemical purity ≈97 ± 0.88 % ITLC, >99 % HPLC, specific activity: 210 ± 5 GBq/mM). {sup 68}Ga-ECC was a water-soluble complex based on partition coefficient data (log P; −1.378) and was stable in the presence of human serum for 2 h at 37 °C. The biodistribution of the tracer demonstrated high kidney excretion of the tracer in 10–20 min. The SUV{sub max} ratios of the liver to left kidney were 0.38 and 0.39 for 30 and 90 min, respectively, indicating high kidney uptake. Initial biodistribution results showed significant kidney and urinary excretion of the tracer comparable to that of the homologous {sup 99m}Tc compound. The complex could be a possible PET kidney imaging agent with a fast imaging time.

  18. Valine-based biphenylsulphonamide matrix metalloproteinase inhibitors as tumor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Oltenfreiter, Ruth [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium)]. E-mail: ruth.oltenfreiter@ugent.be; Staelens, Ludovicus [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium); Kersemans, Veerle [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium); Cornelissen, Bart [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium); Frankenne, Francis [Laboratory of Tumor and Developmental Biology, University of Liege, Sart-Tilman, Liege (Belgium); Foidart, Jean-Michel [Laboratory of Tumor and Developmental Biology, University of Liege, Sart-Tilman, Liege (Belgium); Wiele, Christophe van de [Division of Nuclear Medicine, Gent University Hospital, De Pintelaan 185, 9000 Gent (Belgium); Slegers, Guido [Faculty of Pharmaceutical Sciences, Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent (Belgium)

    2006-06-15

    Among matrix metalloproteinases (MMPs), the subfamily of gelatinases (MMP-2, MMP-9) is of particular interest due to their ability to degrade type IV collagen and other non-fibrillar collagen domains and proteins such as fibronectin and laminin. Whilst malignant cells often over-express various MMPs, the gelatinases have been most consistently detected in malignant tissues and associated with tumor growth, metastatic potential and angiogenesis. Radiosynthesis of carboxylic (1') and hydroxamic (2') MMPIs resulted in radiochemical yields of 70+/-5% (n=6) and 60+/-5% (n=4), respectively. Evaluation in A549-inoculated athymic mice showed a tumor uptake of 2.0+/-0.7%ID/g (3h p.i.), a tumor/blood ratio of 0.5 and a tumor/muscle ratio of 4.6 at 48hp.i. for 1'. For compound 2' a tumor uptake of 0.7+/-0.2%ID/g (3hp.i.), a tumor/blood ratio of 1.2 and a tumor/muscle ratio of 1.8 at 24hp.i. were observed. HPLC analysis of the blood (plasma) showed no dehalogenation or other metabolites of 1' 2hp.i. For compound 2', 65.4% of intact compound was found in the blood (plasma) and one polar metabolite (31%) was detected whereas in the tumor 91.8% of the accumulated activity was caused by intact compound and only 8.1% by the metabolite. Planar imaging, using a Toshiba GCA-9300A/hg SPECT camera, showed that tumor tissue could be visualized and that image quality improved by decreasing specific activity resulting in lower liver uptake, indicating some degree of saturable binding in the liver. In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that MMP inhibitors could have potential as tumor imaging agents, but that further research is necessary.

  19. Valine-based biphenylsulphonamide matrix metalloproteinase inhibitors as tumor imaging agents

    International Nuclear Information System (INIS)

    Oltenfreiter, Ruth; Staelens, Ludovicus; Kersemans, Veerle; Cornelissen, Bart; Frankenne, Francis; Foidart, Jean-Michel; Wiele, Christophe van de; Slegers, Guido

    2006-01-01

    Among matrix metalloproteinases (MMPs), the subfamily of gelatinases (MMP-2, MMP-9) is of particular interest due to their ability to degrade type IV collagen and other non-fibrillar collagen domains and proteins such as fibronectin and laminin. Whilst malignant cells often over-express various MMPs, the gelatinases have been most consistently detected in malignant tissues and associated with tumor growth, metastatic potential and angiogenesis. Radiosynthesis of carboxylic (1') and hydroxamic (2') MMPIs resulted in radiochemical yields of 70+/-5% (n=6) and 60+/-5% (n=4), respectively. Evaluation in A549-inoculated athymic mice showed a tumor uptake of 2.0+/-0.7%ID/g (3h p.i.), a tumor/blood ratio of 0.5 and a tumor/muscle ratio of 4.6 at 48hp.i. for 1'. For compound 2' a tumor uptake of 0.7+/-0.2%ID/g (3hp.i.), a tumor/blood ratio of 1.2 and a tumor/muscle ratio of 1.8 at 24hp.i. were observed. HPLC analysis of the blood (plasma) showed no dehalogenation or other metabolites of 1' 2hp.i. For compound 2', 65.4% of intact compound was found in the blood (plasma) and one polar metabolite (31%) was detected whereas in the tumor 91.8% of the accumulated activity was caused by intact compound and only 8.1% by the metabolite. Planar imaging, using a Toshiba GCA-9300A/hg SPECT camera, showed that tumor tissue could be visualized and that image quality improved by decreasing specific activity resulting in lower liver uptake, indicating some degree of saturable binding in the liver. In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that MMP inhibitors could have potential as tumor imaging agents, but that further research is necessary

  20. Radioiodination of central nerves system dopamine D2 receptor imaging agent. IBZM preparation and preclinical study

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong; Hu Mingyang; Pan Shangren; Wang Bocheng

    1996-01-01

    To study preparation of central nerves system dopamine D2 imaging agent 131 I-IBZM and its preclinical investigation, peracetic acid was used as the oxidant for preparing radioiodinated 125 I-IBZM and 131 I-IBZM, D2 binding properties of IBZM were examined by in vitro binding saturation analysis, rat whole body and regional brain biodistribution, rat brain autoradiography and rabbit SPECT static imaging, etc. The results are: 1. The radiolabelling yields of 125 I-IBZM and 131 I-IBZM were 84.18% +- 3.06% and 78.50% +- 3.47%. The radiochemical purity were over 95% after being isolated by HPLC; and were over 90% after being isolated by organic extraction. 2. Scatchard plot of D2 receptor saturation binding analysis showed: K d = 0.53 +- 0.06 nmol/L, B max = 466.45 +- 45.88 fmol/mg protein. 3. The rat brain autoradiography and analysis showed that there was high 125 I-IBZM uptake in striatal area 2 hr after injection, the striatal/cerebellum ratio was 6.22 +- 0.48; the high 125 -IBZM uptake can be blocked by haloperidol--a special dopamine D2 receptor antagonist. 4. 131 I-IBZM rat biodistribution and rabbit SPECT planar imaging showed good initial brain uptake and retention, the initial uptake of rat brain was 1.893 +- 0.147% ID/g at 2 min and 1.044 +- 0.135% ID/g at 60 min. The results showed that the radioiodinated IBZM had high affinity, saturation and specificity to rat's and rabbit's central nerves system dopamine D2 receptors

  1. Radioiodination of central nerves system dopamine D2 receptor imaging agent. IBZM preparation and preclinical study

    Energy Technology Data Exchange (ETDEWEB)

    Yansong, Lin; Xiangtong, Lin; Mingyang, Hu; Shangren, Pan; Bocheng, Wang [Huashan Hospital of Shanghai Medical Univ., Shanghai (China)

    1996-11-01

    To study preparation of central nerves system dopamine D2 imaging agent {sup 131}I-IBZM and its preclinical investigation, peracetic acid was used as the oxidant for preparing radioiodinated {sup 125}I-IBZM and {sup 131}I-IBZM, D2 binding properties of IBZM were examined by in vitro binding saturation analysis, rat whole body and regional brain biodistribution, rat brain autoradiography and rabbit SPECT static imaging, etc. The results are: 1. The radiolabelling yields of {sup 125}I-IBZM and {sup 131}I-IBZM were 84.18% +- 3.06% and 78.50% +- 3.47%. The radiochemical purity were over 95% after being isolated by HPLC; and were over 90% after being isolated by organic extraction. 2. Scatchard plot of D2 receptor saturation binding analysis showed: K{sub d} = 0.53 +- 0.06 nmol/L, B{sub max} = 466.45 +- 45.88 fmol/mg protein. 3. The rat brain autoradiography and analysis showed that there was high {sup 125}I-IBZM uptake in striatal area 2 hr after injection, the striatal/cerebellum ratio was 6.22 +- 0.48; the high {sup 125}-IBZM uptake can be blocked by haloperidol--a special dopamine D2 receptor antagonist. 4. {sup 131}I-IBZM rat biodistribution and rabbit SPECT planar imaging showed good initial brain uptake and retention, the initial uptake of rat brain was 1.893 +- 0.147% ID/g at 2 min and 1.044 +- 0.135% ID/g at 60 min. The results showed that the radioiodinated IBZM had high affinity, saturation and specificity to rat`s and rabbit`s central nerves system dopamine D2 receptors.

  2. Technique: imaging earliest tooth development in 3D using a silver-based tissue contrast agent.

    Science.gov (United States)

    Raj, Muhammad T; Prusinkiewicz, Martin; Cooper, David M L; George, Belev; Webb, M Adam; Boughner, Julia C

    2014-02-01

    Looking in microscopic detail at the 3D organization of initiating teeth within the embryonic jaw has long-proved technologically challenging because of the radio-translucency of these tiny un-mineralized oral tissues. Yet 3D image data showing changes in the physical relationships among developing tooth and jaw tissues are vital to understand the coordinated morphogenesis of vertebrate teeth and jaws as an animal grows and as species evolve. Here, we present a new synchrotron-based scanning solution to image odontogenesis in 3D and in histological detail using a silver-based contrast agent. We stained fixed, intact wild-type mice aged embryonic (E) day 10 to birth with 1% Protargol-S at 37°C for 12-32 hr. Specimens were scanned at 4-10 µm pixel size at 28 keV, just above the silver K-edge, using micro-computed tomography (µCT) at the Canadian Light Source synchrotron. Synchrotron µCT scans of silver-stained embryos showed even the earliest visible stages of tooth initiation, as well as many other tissue types and structures, in histological detail. Silver stain penetration was optimal for imaging structures in intact embryos E15 and younger. This silver stain method offers a powerful yet straightforward approach to visualize at high-resolution and in 3D the earliest stages of odontogenesis in situ, and demonstrates the important of studying the tooth organ in all three planes of view. Copyright © 2013 Wiley Periodicals, Inc.

  3. Improved identification of cranial nerves using paired-agent imaging: topical staining protocol optimization through experimentation and simulation

    Science.gov (United States)

    Torres, Veronica C.; Wilson, Todd; Staneviciute, Austeja; Byrne, Richard W.; Tichauer, Kenneth M.

    2018-03-01

    Skull base tumors are particularly difficult to visualize and access for surgeons because of the crowded environment and close proximity of vital structures, such as cranial nerves. As a result, accidental nerve damage is a significant concern and the likelihood of tumor recurrence is increased because of more conservative resections that attempt to avoid injuring these structures. In this study, a paired-agent imaging method with direct administration of fluorophores is applied to enhance cranial nerve identification. Here, a control imaging agent (ICG) accounts for non-specific uptake of the nerve-targeting agent (Oxazine 4), and ratiometric data analysis is employed to approximate binding potential (BP, a surrogate of targeted biomolecule concentration). For clinical relevance, animal experiments and simulations were conducted to identify parameters for an optimized stain and rinse protocol using the developed paired-agent method. Numerical methods were used to model the diffusive and kinetic behavior of the imaging agents in tissue, and simulation results revealed that there are various combinations of stain time and rinse number that provide improved contrast of cranial nerves, as suggested by optimal measures of BP and contrast-to-noise ratio.

  4. Pre-clinical evaluation of a nanoparticle-based blood-pool contrast agent for MR imaging of the placenta.

    Science.gov (United States)

    Ghaghada, Ketan B; Starosolski, Zbigniew A; Bhayana, Saakshi; Stupin, Igor; Patel, Chandreshkumar V; Bhavane, Rohan C; Gao, Haijun; Bednov, Andrey; Yallampalli, Chandrasekhar; Belfort, Michael; George, Verghese; Annapragada, Ananth V

    2017-09-01

    Non-invasive 3D imaging that enables clear visualization of placental margins is of interest in the accurate diagnosis of placental pathologies. This study investigated if contrast-enhanced MRI performed using a liposomal gadolinium blood-pool contrast agent (liposomal-Gd) enables clear visualization of the placental margins and the placental-myometrial interface (retroplacental space). Non-contrast MRI and contrast-enhanced MRI using a clinically approved conventional contrast agent were used as comparators. Studies were performed in pregnant rats under an approved protocol. MRI was performed at 1T using a permanent magnet small animal scanner. Pre-contrast and post-liposomal-Gd contrast images were acquired using T1-weighted and T2-weighted sequences. Dynamic Contrast enhanced MRI (DCE-MRI) was performed using gadoterate meglumine (Gd-DOTA, Dotarem ® ). Visualization of the retroplacental clear space, a marker of normal placentation, was judged by a trained radiologist. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated for both single and averaged acquisitions. Images were reviewed by a radiologist and scored for the visualization of placental features. Contrast-enhanced CT (CE-CT) imaging using a liposomal CT agent was performed for confirmation of the MR findings. Transplacental transport of liposomal-Gd was evaluated by post-mortem elemental analysis of tissues. Ex-vivo studies in perfused human placentae from normal, GDM, and IUGR pregnancies evaluated the transport of liposomal agent across the human placental barrier. Post-contrast T1w images acquired with liposomal-Gd demonstrated significantly higher SNR (p = 0.0002) in the placenta compared to pre-contrast images (28.0 ± 4.7 vs. 6.9 ± 1.8). No significant differences (p = 0.39) were noted between SNR in pre-contrast and post-contrast liposomal-Gd images of the amniotic fluid, indicating absence of transplacental passage of the agent. The placental margins were

  5. New calcium-selective smart contrast agents for magnetic resonance imaging.

    Science.gov (United States)

    Verma, Kirti Dhingra; Forgács, Attila; Uh, Hyounsoo; Beyerlein, Michael; Maier, Martin E; Petoud, Stéphane; Botta, Mauro; Logothetis, Nikos K

    2013-12-23

    Calcium plays a vital role in the human body and especially in the central nervous system. Precise maintenance of Ca(2+) levels is very crucial for normal cell physiology and health. The deregulation of calcium homeostasis can lead to neuronal cell death and brain damage. To study this functional role played by Ca(2+) in the brain noninvasively by using magnetic resonance imaging, we have synthesized a new set of Ca(2+) -sensitive smart contrast agents (CAs). The agents were found to be highly selective to Ca(2+) in the presence of other competitive anions and cations in buffer and in physiological fluids. The structure of CAs comprises Gd(3+)-DO3A (DO3A=1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) coupled to a Ca(2+) chelator o-amino phenol-N,N,O-triacetate (APTRA). The agents are designed to sense Ca(2+) present in extracellular fluid of the brain where its concentration is relatively high, that is, 1.2-0.8 mM. The determined dissociation constant of the CAs to Ca(2+) falls in the range required to sense and report changes in extracellular Ca(2+) levels followed by an increase in neural activity. In buffer, with the addition of Ca(2+) the increase in relaxivity ranged from 100-157%, the highest ever known for any T1-based Ca(2+)-sensitive smart CA. The CAs were analyzed extensively by the measurement of luminescence lifetime measurement on Tb(3+) analogues, nuclear magnetic relaxation dispersion (NMRD), and (17)O NMR transverse relaxation and shift experiments. The results obtained confirmed that the large relaxivity enhancement observed upon Ca(2+) addition is due to the increase of the hydration state of the complexes together with the slowing down of the molecular rotation and the retention of a significant contribution of the water molecules of the second sphere of hydration. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Oral gadopentetate dimeglumine administration as a negative gastrointestinal contrast agent to improve image quality of MR cholangiopancreatography

    International Nuclear Information System (INIS)

    Chen Yi; Xu Yikai; Zhao Yuhui; Wang Guisheng

    2008-01-01

    Objective: To choose optimal concentration and volume of Gd-DTPA solution as a oral gastrointestinal negative contrast agent for MRCP. To evaluate the role of Gd-DTPA solution in improving image quality of MRCP. Methods: In vitro experiment: Gd-DTPA solution was made with different concentrations. T 1 WI, T 2 WI, two-dimensional single slice fast spin echo sequence and three-dimensional half-fourier acquisition single-shot fast spin echo sequence were performed to measure the signal intensity of these contrast agents respectively, so Gd-DTPA solution with the optimal concentration can be decided as oral negative gastrointestinal contrast agent on MRCP. Clinical study: The Gd-DTPA solution with optimal concentration and volume was regarded as an oral negative gastrointestinal contrast agent of MRCP. Twenty- four' patients were performed with MRCP before and after (5-10 minutes and 10-15 minutes) administration of oral negative gastrointestinal contrast agent and image quality was analyzed. Statistical analysis was performed using analysis of variance with SPSS 10.0. Results: When the concentration of Gd-DTPA solution was ≤0.01 mol/L, the contrast agent was hyperintense on T 1 WI. On T 2 WI, when the concentration was ≥0.015 mol/L, it was as hypointense as basic ground; On 2D FSE MRCP images, controls were hyperintense and the contrast agent with concentration ranging from 0.0025 mol/L to 0.03 mol/L was hypointense. On 3D HEAST MRCP image, controls were hyperintense and when the concentration of Gd-DTPA was ≥0.01 mol, the contrast agent was hypointense. The Gd-DTPA solution with the concentration of 0.01 mol/L and the volume of 100 ml was chosen as MRCP oral negative gastrointestinal contrast agent. On MRCP images after oral administration of the contrast agent, in 10-15 minutes, the average grade scores within 24 patients of the intrahepatic bile duct, the common hepatic bile duct, the gall bladder, the common bile duct and pancreatic duct (the average grade

  7. Near infrared spectral polarization imaging of prostate cancer tissues using Cybesin: a receptor-targeted contrast agent

    Science.gov (United States)

    Pu, Yang; Wang, W. B.; Tang, G. C.; Liang, Kexian; Achilefu, S.; Alfano, R. R.

    2013-03-01

    Cybesin, a smart contrast agent to target cancer cells, was investigated using a near infrared (NIR) spectral polarization imaging technique for prostate cancer detection. The approach relies on applying a contrast agent that can target cancer cells. Cybesin, as a small ICG-derivative dye-peptide, emit fluorescence between 750 nm and 900 nm, which is in the "tissue optical window". Cybesin was reported targeting the over-expressed bombesin receptors in cancer cells in animal model and the human prostate cancers over-expressing bombesin receptors. The NIR spectral polarization imaging study reported here demonstrated that Cybesin can be used as a smart optical biomarker and as a prostate cancer receptor targeted contrast agent.

  8. Carbon Nano-Allotrope/Magnetic Nanoparticle Hybrid Nanomaterials as T2 Contrast Agents for Magnetic Resonance Imaging Applications

    Directory of Open Access Journals (Sweden)

    Yunxiang Gao

    2018-02-01

    Full Text Available Magnetic resonance imaging (MRI is the most powerful tool for deep penetration and high-quality 3D imaging of tissues with anatomical details. However, the sensitivity of the MRI technique is not as good as that of the radioactive or optical imaging methods. Carbon-based nanomaterials have attracted significant attention in biomaterial research in recent decades due to their unique physical properties, versatile functionalization chemistry, as well as excellent biological compatibility. Researchers have employed various carbon nano-allotropes to develop hybrid MRI contrast agents for improved sensitivity. This review summarizes the new research progresses in carbon-based hybrid MRI contrast agents, especially those reported in the past five years. The review will only focus on T2-weighted MRI agents and will be categorized by the different carbon allotrope types and magnetic components. Considering the strong trend in recent bio-nanotechnology research towards multifunctional diagnosis and therapy, carbon-based MRI contrast agents integrated with other imaging modalities or therapeutic functions are also covered.

  9. Multivalent contrast agents based on Gd-DTPA-terminated poly (propylene imine) dendrimers for Magnetic Resonance Imaging

    NARCIS (Netherlands)

    Langereis, S.; Lussanet, de Q.G; Genderen, van M.H.P.; Backes, W.H.; Meijer, E.W.

    2004-01-01

    A convenient methodol. has been developed for the synthesis of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-terminated poly(propylene imine) dendrimers as contrast agents for magnetic resonance imaging (MRI). In our strategy, isocyanate-activated, tert-butyl-protected DTPA analogs were

  10. Radioiodinate labeling of atherosclerotic plaque imaging agent SP-4 and preliminary experiments

    International Nuclear Information System (INIS)

    Zhang, Y.; Wu, Z.

    2000-01-01

    SP-4 was oligopeptide contained 18 amino-acid. It was a part of apolipoprotein B. To study labeling SP-4 with 131 I and its clinical prospect as an atherosclerotic plaque imaging agent. SP-4 was synthesized by solid phase method and identified by amino acid analysis after purification with preparation-model HPLC. SP-4 was labeled with 131 I by the Chloramine-T method and purified through Sephadex G-25, then the radiochemical purity of 131 SP-4 and its stability in vitro were analyzed. 12 New Zealand rabbits were divided into atherosclerosis group (n=7, group A) and control group (n=5, group B). All of them were administrated with bovine serum albumen through i.v., then the rabbits of group A were fed on high cholesterol and high fat diet and group B, on normal diet. Purified 131 I-SP-4 was injected intravenously. %ID/g in blood and thoracic aorta and abdominal aorta at 4 hrs after injection and biodistribution of 131 I-SP-4 was investigated. The amino acid formation of the pure product was identified to be correct through amino-acid analysis. The radiochemical purity of 131 I-SP-4 was 96.2% after being purified, but less than 90% after being stored for 20 hrs. One of 7 rabbits in group A died after being fed for three weeks, the others were alive and atherosclerotic lesions were found after being fed for two mon. On the contrary, 5 rabbits in group B were visualized not to have atherosclerotic lesions. The uptakes of group A and group B at 4 hr after injection were 0.0378±0.0028 and 0.0371±0.038 in blood (p>0.05), 0.0882 ±0.0101 and 0.0276 ±0.0044 in abdominal aorta (p 131 I-SP-4 was mainly excreted through kidneys. SP-4 remained its biological activity after radioiodination and was located at atherosclerotic lesions. It was potentially useful as an atherosclerotic plaque imaging agent

  11. Development and evaluation of a novel radioiodinated vesamicol analog as a sigma receptor imaging agent.

    Science.gov (United States)

    Ogawa, Kazuma; Kanbara, Hiroya; Shiba, Kazuhiro; Kitamura, Yoji; Kozaka, Takashi; Kiwada, Tatsuto; Odani, Akira

    2012-09-28

    Sigma receptors are highly expressed in human tumors and should be appropriate targets for developing tumor imaging agents. Previously, we synthesized a vesamicol analog, (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol ((+)-pIV), with a high affinity for sigma receptors and prepared radioiodinated (+)-pIV. As a result, (+)-[125I]pIV showed high tumor uptake in biodistribution experiments. However, the accumulation of radioactivity in normal tissues, such as the liver, was high. We supposed that some parts of the accumulation of (+)-pIV in the liver should be because of its high lipophilicity, and prepared and evaluated a more hydrophilic radiolabeled vesamicol analog, (+)-4-[1-(2-hydroxycyclohexyl)piperidine-4-yl]-2-iodophenol ((+)-IV-OH). (+)-[125I]IV-OH was prepared by the chloramine T method from the precursor. The partition coefficient of (+)-[125I]IV-OH was measured. Biodistribution experiments were performed by intravenous administration of a mixed solution of (+)-[125I]IV-OH and (+)-[131I]pIV into DU-145 tumor-bearing mice. Blocking studies were performed by intravenous injection of (+)-[125I]IV-OH mixed with an excess amount of ligand into DU-145 tumor-bearing mice. The hydrophilicity of (+)-[125I]IV-OH was much higher than that of (+)-[125I]pIV. In biodistribution experiments, (+)-[125I]IV-OH and (+)-[131I]pIV showed high uptake in tumor tissues at 10-min post-injection. Although (+)-[131I]pIV tended to be retained in most tissues, (+)-[125I]IV-OH was cleared from most tissues. In the liver, the radioactivity level of (+)-[125I]IV-OH was significantly lower at all time points compared to those of (+)-[131I]pIV. In the blocking studies, co-injection of an excess amount of sigma ligands resulted in significant decreases of tumor/blood uptake ratios after injection of (+)-[125I]IV-OH. The results indicate that radioiodinated (+)-IV-OH holds a potential as a sigma receptor imaging agent.

  12. Radiolabeled enzyme inhibitors and binding agents targeting PSMA: Effective theranostic tools for imaging and therapy of prostate cancer

    International Nuclear Information System (INIS)

    Pillai, Maroor Raghavan Ambikalmajan; Nanabala, Raviteja; Joy, Ajith; Sasikumar, Arun; Knapp, Furn F.

    2016-01-01

    Because of the broad incidence, morbidity and mortality associated with prostate-derived cancer, the development of more effective new technologies continues to be an important goal for the accurate detection and treatment of localized prostate cancer, lymphatic involvement and metastases. Prostate-specific membrane antigen (PSMA; Glycoprotein II) is expressed in high levels on prostate-derived cells and is an important target for visualization and treatment of prostate cancer. Radiolabeled peptide targeting technologies have rapidly evolved over the last decade and have focused on the successful development of radiolabeled small molecules that act as inhibitors to the binding of the N-acetyl-L-aspartyl-L-glutamate (NAAG) substrate to the PSMA molecule. A number of radiolabeled PSMA inhibitors have been described in the literature and labeled with SPECT, PET and therapeutic radionuclides. Clinical studies with these agents have demonstrated the improved potential of PSMA-targeted PET imaging agents to detect metastatic prostate cancer in comparison with conventional imaging technologies. Although many of these agents have been evaluated in humans, by far the most extensive clinical literature has described use of the 68 Ga and 177 Lu agents. This review describes the design and development of these agents, with a focus on the broad clinical introduction of PSMA targeting motifs labeled with 68 Ga for PET-CT imaging and 177 Lu for therapy. In particular, because of availability from the long-lived 68 Ge (T 1/2 = 270 days)/ 68 Ga (T 1/2 = 68 min) generator system and increasing availability of PET-CT, the 68 Ga-labeled PSMA targeted agent is receiving widespread interest and is one of the fastest growing radiopharmaceuticals for PET-CT imaging.

  13. "Smart" gold nanoparticles for photoacoustic imaging: an imaging contrast agent responsive to the cancer microenvironment and signal amplification via pH-induced aggregation.

    Science.gov (United States)

    Song, Jaejung; Kim, Jeesu; Hwang, Sekyu; Jeon, Mansik; Jeong, Sanghwa; Kim, Chulhong; Kim, Sungjee

    2016-07-07

    'Smart' gold nanoparticles can respond to mild acidic environments, rapidly form aggregates, and shift the absorption to red and near-infrared. They were used as a photoacoustic imaging agent responsive to the cancer microenvironment, and have demonstrated the cancer-specific accumulation at the cellular level and an amplified signal which is twice higher than the control in vivo.

  14. Brain hypoxia imaging

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Chun [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2007-04-15

    The measurement of pathologically low levels of tissue pO{sub 2} is an important diagnostic goal for determining the prognosis of many clinically important diseases including cardiovascular insufficiency, stroke and cancer. The target tissues nowadays have mostly been tumors or the myocardium, with less attention centered on the brain. Radiolabelled nitroimidazole or derivatives may be useful in identifying the hypoxic cells in cerebrovascular disease or traumatic brain injury, and hypoxic-ischemic encephalopathy. In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. {sup 18}F-MISO PET and {sup 99m}Tc-EC-metronidazole SPECT in patients with acute ischemic stroke identified hypoxic tissues and ischemic penumbra, and predicted its outcome. A study using {sup 123}I-IAZA in patient with closed head injury detected the hypoxic tissues after head injury. Up till now these radiopharmaceuticals have drawbacks due to its relatively low concentration with hypoxic tissues associated with/without low blood-brain barrier permeability and the necessity to wait a long time to achieve acceptable target to background ratios for imaging in acute ischemic stroke. It is needed to develop new hypoxic marker exhibiting more rapid localization in the hypoxic region in the brain. And then, the hypoxic brain imaging with imidazoles or non-imidazoles may be very useful in detecting the hypoxic tissues, determining therapeutic strategies and developing therapeutic drugs in several neurological disease, especially, in acute ischemic stroke.

  15. Preparation of new technetium-99m NNS/X complexes and selection for brain imaging agent

    Institute of Scientific and Technical Information of China (English)

    HE; Qiange; CHEN; Xiangji; MIAO; Yubin; LIU; Boli

    2004-01-01

    Based on excellent experiment results of 99mTcO-MPBDA-Cl, two new ligands MPTDA and MPDAA are synthesized. Then series of 99mTcO3+ complexes are prepared through adding different halide anions, followed by tests of physical chemistry qualities and biodistribution experiments. And results of these experiments show that complexes formed with MPTDA and MPDAA have better lipophilicity than those formed with MPBDA, still maintain the good brain retention ability of this type of compounds, but radioactivity uptake in blood is higher than that of 99mTcO-MPBDA and ratios of brain/blood are reduced. Obvious affections are fetched out on brain uptake and retention if fluoride, bromide or iodide anions are added. Results of experiments can be explained in reason with theoretic computation. It is confirmed that 99mTcO-MPBDA-Cl has potential to develop a new type of brain imaging agent considering integrated factors such as brain uptake, retention and toxicity.

  16. Solvation effects on brain uptakes of isomers of 99mTc brain imaging agents

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Analysis of electrostatic hydration free energies of the isomers of the 99mTc-BAT and 99mTc-DADT complexes is carried out using the computer simulation technique. The results show that not only a correlation exists between the logarithm of the brain uptake and the electrostatic hydration free energy for the isomers of 99mTc-brain radiopharmaceuticals, but also a linear relationship exists between the logarithm of the ratio of the brain uptake of the syn isomer to that of the anti one and the difference between the electrostatic hydration free energy of the syn-isomer and that of the anti one. Furthermore, the investigation on the important factors influencing the brain uptakes of 99mTc-radiopharmaceuticals and the reasons of the different biodistribution of the isomers of the 99mTc-complexes is explored at the molecular level. The results may provide a reference for the rational drug design of brain imaging agents.

  17. SERS-barcoded colloidal gold NP assemblies as imaging agents for use in biodiagnostics

    Science.gov (United States)

    Dey, Priyanka; Olds, William; Blakey, Idriss; Thurecht, Kristofer J.; Izake, Emad L.; Fredericks, Peter M.

    2014-03-01

    There is a growing need for new biodiagnostics that combine high throughput with enhanced spatial resolution and sensitivity. Gold nanoparticle (NP) assemblies with sub-10 nm particle spacing have the benefits of improving detection sensitivity via Surface enhanced Raman scattering (SERS) and being of potential use in biomedicine due to their colloidal stability. A promising and versatile approach to form solution-stable NP assemblies involves the use of multi-branched molecular linkers which allows tailoring of the assembly size, hot-spot density and interparticle distance. We have shown that linkers with multiple anchoring end-groups can be successfully employed as a linker to assemble gold NPs into dimers, linear NP chains and clustered NP assemblies. These NP assemblies with diameters of 30-120 nm are stable in solution and perform better as SERS substrates compared with single gold NPs, due to an increased hot-spot density. Thus, tailored gold NP assemblies are potential candidates for use as biomedical imaging agents. We observed that the hot-spot density and in-turn the SERS enhancement is a function of the linker polymer concentration and polymer architecture. New deep Raman techniques like Spatially Offset Raman Spectroscopy (SORS) have emerged that allow detection from beneath diffusely scattering opaque materials, including biological media such as animal tissue. We have been able to demonstrate that the gold NP assemblies could be detected from within both proteinaceous and high lipid containing animal tissue by employing a SORS technique with a backscattered geometry.

  18. A Novel Polyacrylamide Magnetic Nanoparticle Contrast Agent for Molecular Imaging using MRI

    Directory of Open Access Journals (Sweden)

    Bradford A. Moffat

    2003-10-01

    Full Text Available A novel Polyacrylamide superparamagnetic iron oxide nanoparticle platform is described which has been synthetically prepared such that multiple crystals of iron oxide are encapsulated within a single Polyacrylamide matrix (PolyAcrylamide Magnetic [PAM] nanoparticles. This formulation provides for an extremely large T2 and T2* relaxivity of between 620 and 1140 sec−1 mM−1. Administration of PAM nanoparticles into rats bearing orthotopic 9L gliomas allowed quantitative pharmacokinetic analysis of the uptake of nanoparticles in the vasculature, brain, and glioma. Addition of polyethylene glycol of varying sizes (0.6, 2, and 10 kDa to the surface of the PAM nanoparticles resulted in an increase in plasma half-life and affected tumor uptake and retention of the nanoparticles as quantified by changes in tissue contrast using MRI. The flexible formulation of these nanoparticles suggests that future modifications could be accomplished allowing for their use as a targeted molecular imaging contrast agent and/or therapeutic platform for multiple indications.

  19. Thallium Labeled Citrate-Coated Prussian Blue Nanoparticles as Potential Imaging Agent

    Directory of Open Access Journals (Sweden)

    Krisztián Szigeti

    2018-01-01

    Full Text Available Background. The aim of this study was to develop and characterize a nanoparticle-based image-contrast platform which is biocompatible, chemically stable, and accessible for radiolabeling with 201Tl. We explored whether this nanoparticle enhanced the T1 signal which might make it an MRI contrast agent as well. Methods. The physical properties of citrate-coated Prussian blue nanoparticles (PBNPs (iron(II;iron(III;octadecacyanide doped with 201Tl isotope were characterized with atomic force microscopy, dynamic light scattering, and zeta potential measurement. PBNP biodistribution was determined by using SPECT and MRI following intravenous administration into C57BL6 mice. Activity concentrations (MBq/cm3 were calculated from the SPECT scans for each dedicated volume of interest (VOI of liver, kidneys, salivary glands, heart, lungs, and brain. Results. PBNP accumulation peaked at 2 hours after injection predominantly in the kidneys and the liver followed by a gradual decrease in activity in later time points. Conclusion. We synthetized, characterized, and radiolabeled a Prussian blue-based nanoparticle platform for contrast material applications. Its in vivo radiochemical stability and biodistribution open up the way for further diagnostic applications.

  20. Synthesis of 18F labeled clotrimazole derivatives as a potential PET imaging agent

    International Nuclear Information System (INIS)

    Jung, Soon Jae; Kim, In Jong; Park, Jeong Hoon; Lee, Heung Nae; Kim, Sang Wook; Hur, Min Goo; Choi, Sang Moo; Yang, Seung Dae; Yu, Kook Hyun

    2010-01-01

    Clotrimazole [1- -1H-imidazole, CLT] has been reported to inhibit the proliferation of vascular endothelial and act as an in vitro anti-VEGF drug. It is also shown to inhibit angiogenesis in an animal model. The radioisotope labeled clotrimazole derivative can be utilized to monitor the physiologic processes of cancer. In this study, we synthesized [ 18 F]fluoride labeled clotrimazole derivatives as a new tumor imaging agent for PET. The references were prepared by a refluxing with clotrimazole and an excess of fluoroalkyltosylate in acetonitrile for 36 h and clotrimazole reacted with ditosylalkane to give precursors. [ 18 ]Fluoride labeled reaction was performed with precursor in Kryptofix[2.2.2]/K 2 CO 3 for 10 min at 80 .deg. C. The radiolabeling mixture was passed through a silica Sep-Pak cartridge to remove 18 F - . The [ 18 ]F-clotrimazole derivatives were synthesized with a 20 ∼ 25% yield. In the radiofluoriantion step, we used acetonitrile and DMSO as a solvent and observed a higher at the acetonitrile (25%) reaction compared with the DMSO reaction (5%)

  1. An improved synthesis of 4-[18F]-ADAM, a potent serotonin transporter imaging agent

    International Nuclear Information System (INIS)

    Huang, Y.-Y.; Huang, W.-S.; Chu, T.-C.; Shiue, C.-Y.

    2009-01-01

    An improved synthesis of N,N-dimethyl-2-(2-amino-4-[ 18 F]fluorophenylthio)benzylamine (4-[ 18 F]-ADAM, 2) as a potent serotonin transporter (SERT) imaging agent is described. Molecular orbital (MO) calculation predicts that N,N-dimethyl-2- (2-nitro-4-trimethylammoniumtrifluoromethanesulfonylphenylthio)benzamide (8) is probably a better precursor than N,N-dimethyl-2-(2,4-dinitrophenylthio)benzylamine (1) for preparing 2. Radioligand 2 was synthesized by the reaction of either precursor 1 or precursor 8 with K[ 18 F]/K 2.2.2 at 120 deg. C followed by reduction with BH 3 at 80 deg. C. The radiochemical yield (EOB) of 2 synthesized from precursor 1 and 8 was 5.7±2.4% (n=6) and 14.8±4.0% (n=5), respectively, in a synthesis time of 120 min from EOB. The specific activity of 2 was 3 Ci/μmol or 111 GBq/μmol (EOB). Thus, this new synthetic method has significantly improved the radiochemical yield of 4-[ 18 F]-ADAM and makes this radioligand more accessible to PET Centers without a cyclotron.

  2. An improved synthesis of 4-[{sup 18}F]-ADAM, a potent serotonin transporter imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Y.-Y. [PET Center, Department of Nuclear Medicine, Tri-Service General Hospital 325 Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan (China); Department of Biomedical Engineering and Environmental Sciences, National Thising Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Huang, W.-S. [PET Center, Department of Nuclear Medicine, Tri-Service General Hospital 325 Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan (China); Chu, T.-C. [Department of Biomedical Engineering and Environmental Sciences, National Thising Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Shiue, C.-Y. [PET Center, Department of Nuclear Medicine, Tri-Service General Hospital 325 Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan (China)], E-mail: shiue@ndmctsgh.edu.tw

    2009-06-15

    An improved synthesis of N,N-dimethyl-2-(2-amino-4-[{sup 18}F]fluorophenylthio)benzylamine (4-[{sup 18}F]-ADAM, 2) as a potent serotonin transporter (SERT) imaging agent is described. Molecular orbital (MO) calculation predicts that N,N-dimethyl-2- (2-nitro-4-trimethylammoniumtrifluoromethanesulfonylphenylthio)benzamide (8) is probably a better precursor than N,N-dimethyl-2-(2,4-dinitrophenylthio)benzylamine (1) for preparing 2. Radioligand 2 was synthesized by the reaction of either precursor 1 or precursor 8 with K[{sup 18}F]/K{sub 2.2.2} at 120 deg. C followed by reduction with BH{sub 3} at 80 deg. C. The radiochemical yield (EOB) of 2 synthesized from precursor 1 and 8 was 5.7{+-}2.4% (n=6) and 14.8{+-}4.0% (n=5), respectively, in a synthesis time of 120 min from EOB. The specific activity of 2 was 3 Ci/{mu}mol or 111 GBq/{mu}mol (EOB). Thus, this new synthetic method has significantly improved the radiochemical yield of 4-[{sup 18}F]-ADAM and makes this radioligand more accessible to PET Centers without a cyclotron.

  3. Technetium-99m p-iodophenethyldiaminodithiol (DADT-IPE): potential brain perfusion imaging agent for SPECT

    International Nuclear Information System (INIS)

    Shiba, K.; Mori, H.; Matsuda, H.; Hisada, K.

    1992-01-01

    A new ligand, an N-p-iodophenethyl diaminodithiol (DADT-IPE), an analog of N-isopropyl-p-iodoamphetamine (IMP), was synthesized and subsequently complexed with 99m Tc, using stannous chloride as a reducing agent. Two complexes (a and b) were separated from 99m Tc-DADT-IPE by high performance liquid chromatography (HPLC). Competitive inhibition studies showed that the IC 50 value of DADT-IPE (70 μM) was similar to that of IMP (49 μM). Biodistribution studies of one of the complexes [ 99m Tc-DADT-IPE(a)] in rats showed that 0.65% of the injected dose of the tracer remained in the brain at 5 min after intravenous injection, with 0.53% of the dose remaining in the brain at 60 min post-injection, whereas the corresponding values for the other complex [ 99m Tc-DADT-IPE(b)] were 0.34% dose in the brain at 5 min and 0.28% dose in the brain at 60 min post-injection. The half-life for clearance of 99m Tc-DADT-IPE(a) from rat brain was found to be more than 5h. These results suggested that 99m Tc-DADT-IPE(a) has characteristics which are suitable for cerebral perfusion imaging. (author)

  4. Contrast-enhanced CT with a High-Affinity Cationic Contrast Agent for Imaging ex Vivo Bovine, Intact ex Vivo Rabbit, and in Vivo Rabbit Cartilage

    OpenAIRE

    Stewart, Rachel C.; Bansal, Prashant N.; Entezari, Vahid; Lusic, Hrvoje; Nazarian, Rosalynn M.; Snyder, Brian D.; Grinstaff, Mark W.

    2013-01-01

    The high affinity of a cationic iodinated contrast agent for cartilage provides better tissue visualization, easier segmentation, higher contrast-to-noise ratios, and longer usable imaging windows and requires a lower dose of injected contrast agent compared with an anionic contrast agent.

  5. 99mTc-O2S4: a new generation hepatobiliary imaging agent

    International Nuclear Information System (INIS)

    Babbar, A.K.; Mathur, R.; Katiyar, N.; Dutta, M.; Flora; Mishra, A.K.; Yadav, A.

    2010-01-01

    Full text: Hepatobiliary imaging radionuclide - 99m Tc-Mebrofenin is indicated as a hepatobiliary imaging agent for the evaluation of hepatobiliary tract patency to differentiate jaundice resulting from hepatocellular causes from jaundice resulting from partial or complete biliary obstruction; to differentiate extrahepatic biliary atresia from neonatal hepatitis; to detect cystic duct obstruction associated with acute cholecystitis; and to detect bile leaks. Also, 99m Tc-Mebrofenin may be useful to detect intrahepatic cholestasis and to distinguish it from other hepatobiliary diseases, which involve hepatocyte damage. However, the Mebrofenin kit has to be obtained at an exorbitant cost and there was need to develop an indigenous kit that was readily available and could give similar results. For the first time in India, a derivative of DMSA developed by DRDE, Gwalior and modified at INMAS, Delhi to adopt early transition metals, was successfully labelled with 99m Tc (LE>99%). The reaction conditions were optimized after studying the effects of amount of SnCl 2 , pH of the reaction and effect of incubation time. The labelled product 99m Tc-O 2 S 4 , was characterized by ITLC-SG using acetone and saline. The complex was found to be fairly stable at room temperature and showed>95% plasma protein binding. The biodistribution studies showed that after intravenous administration, there was immediate accumulation of radioactivity in liver, the activity kept on increasing in gall bladder with time and thereafter the radioactivity moved to common bile duct (CBD) and small intestines. No significant radioactivity was found in kidneys and blood. Clear visualization of the gallbladder and intestines, within 15 to 45 minutes of administration of 99m Tc-O 2 S 4 in normal rabbit, demonstrates hepatobiliary tract patency of the newly developed radiotracer. The dynamic and static images showed that the newly developed radiopharmaceutical 99m Tc-O 2 S 4 has full potential in studying

  6. Three-dimensional imaging of the aortic vessel wall using an elastin-specific magnetic resonance contrast agent.

    Science.gov (United States)

    Makowski, Marcus R; Preissel, Anne; von Bary, Christian; Warley, Alice; Schachoff, Sylvia; Keithan, Alexandra; Cesati, Richard R; Onthank, David C; Schwaiger, Markus; Robinson, Simon P; Botnar, René M

    2012-07-01

    The aim of this study was to demonstrate the feasibility of high-resolution 3-dimensional aortic vessel wall imaging using a novel elastin-specific magnetic resonance contrast agent (ESMA) in a large animal model. The thoracic aortic vessel wall of 6 Landrace pigs was imaged using a novel ESMA and a nonspecific control agent. On day 1, imaging was performed before and after the administration of a nonspecific control agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA; Bayer Schering AG, Berlin, Germany). On day 3, identical scans were repeated before and after the administration of a novel ESMA (Lantheus Medical Imaging, North Billerica, Massachusetts). Three-dimensional inversion recovery gradient echo delayed-enhancement imaging and magnetic resonance (MR) angiography of the thoracic aortic vessel wall were performed on a 1.5-T MR scanner (Achieva; Philips Medical Systems, the Netherlands). The signal-to-noise ratio and the contrast-to-noise ratio of arterial wall enhancement, including the time course of enhancement, were assessed for ESMA and Gd-DTPA. After the completion of imaging sessions, histology, electron microscopy, and inductively coupled plasma mass spectroscopy were performed to localize and quantify the gadolinium bound to the arterial vessel wall. Administration of ESMA resulted in a strong enhancement of the aortic vessel wall on delayed-enhancement imaging, whereas no significant enhancement could be measured with Gd-DTPA. Ninety to 100 minutes after the administration of ESMA, significantly higher signal-to-noise ratio and contrast-to-noise ratio could be measured compared with the administration of Gd-DTPA (45.7 ± 9.6 vs 13.2 ± 3.5, P wall imaging using a novel ESMA in a large animal model under conditions resembling a clinical setting. Such an approach could be useful for the fast 3-dimensional assessment of the arterial vessel wall in the context of atherosclerosis, aortic aneurysms, and hypertension.

  7. Hypoxic hypoxia as a means of modifying radiosensibility

    International Nuclear Information System (INIS)

    Neumeister, K.; Niemiec, C.; Bolck, M.; Jahns, J.; Kamprad, F.; Arnold, P.; Johannsen, U.; Koch, F.; Mehlhorn, G.

    1977-01-01

    Following an overview of the various possibilities of creating hypoxia in mammals, the problem of reducing radioresistance of hypoxic tumor cells is treated. Furthermore, the results of irradiation experiments with mice, rats and pigs breathing hypoxic mixtures of O 2 and N 2 are given and discussed with a view to applying hypoxic hypoxia in the radiotherapy of human tumors. (author)

  8. Further characterization of 4-bromomisonidazole as a potential detector of hypoxic cells

    International Nuclear Information System (INIS)

    Rasey, J.S.; Krohn, K.A.; Grunbaum, Z.; Conroy, P.J.; Bauer, K.; Sutherland, R.M.

    1985-01-01

    [ 14 C]Bromomisonidazole was prepared by direct bromination of [ring-2] [ 14 C]misonidazole in dioxane. The uptake and binding of the two labeled sensitizers were compared in vitro in 1-mm EMT-6 spheroids which contain a necrotic core. Using liquid scintillation counting it was shown that spheroids incubated with 50 μM [ 14 C]bromomisonidazole concentrated drug above levels in the medium by 1 1/2 hr and achieved maximum concentration by 10 hr with no further increase at 23 hr. Spheroids incubated with 50 μM[ 14 C]misonidazole may concentrate the sensitizer more slowly but ultimately reached the same fivefold increase over levels in the medium by 23 hr as was observed for bromomisonidazole. Autoradiographs prepared from spheroids after incubation with [ 14 C]misonidazole or [ 14 C]bromomisonidazole showed silver grains preferentially located over viable hypoxic cells in the inner half of the spheroid rim adjacent to the necrotic center, with lower grain density over nonviable necrotic areas and many fewer grains over oxic cells at the periphery of the spheroid. The data support the potential of radiolabled bromomisonidazole for in vivo imaging pending additional studies of the metabolism of this agent

  9. Harmonic US imaging of vesicoureteric reflux in children: usefulness of a second generation US contrast agent.

    Science.gov (United States)

    Ascenti, Giorgio; Zimbaro, Giovanni; Mazziotti, Silvio; Chimenz, Roberto; Fede, Carmelo; Visalli, Carmela; Scribano, Emanuele

    2004-06-01

    Contrast-enhanced voiding urosonography (VUS) is largely accepted both for the diagnosis and follow-up of vesicoureteric reflux (VUR) in children. To evaluate the usefulness of contrast-enhanced second-harmonic VUS in the diagnosis and grading of VUR, using a second-generation contrast agent. Eighty consecutive children were prospectively studied with contrast-enhanced second-harmonic VUS. All children received a second-generation contrast medium, constituted by phospholipid-stabilized microbubbles of sulphur-hexafluoride (SonoVue, Bracco, Milan, Italy). US monitoring of the bladder, of the retrovesical space and of the kidneys was performed using, alternatively, both tissue-harmonic and contrast-harmonic modes. In those young boys where VUR was depicted at VUS, examination was completed with transperineal, sagittal urethral exploration during micturition. VUR was graded in five steps and diagnoses were compared with voiding cystourethrography (VCUG). VUR was diagnosed in 52 reno-ureteral units with VUS. In 49 of these reno-ureteral units, VCUG confirmed the presence of VUR. In comparison to VUS, sensitivity and negative predictive value of VCUG were inferior. The grade of VUR detected at VUS was higher than that detected at VCUG in three units. In no case was the grade of VUR detected at VCUG higher than the one detected at VUS. The differences between VUS and VCUG in grading VUR were statistically significant (p=0.02). Imaging of the normal posterior urethra was skilfully demonstrated with US in 15 young boys with VUR. No statistically significant differences were found between tissue-harmonic and contrast-harmonic mode (p=0.102). Contrast-enhanced second-harmonic VUS is a sensitive and easy technique for the evaluation of VUR. A second-generation US contrast medium such as SonoVue, if available, should be the first choice as the dose required for one examination is much lower and consequently significant reduction of contrast agent cost is possible. Copyright

  10. {sup 18}F-Labelled metomidate analogues as adrenocortical imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Erlandsson, Maria; Karimi, Farhad [Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, S-751 23 Uppsala (Sweden); Lindhe, Orjan [Uppsala Imanet, GE Healthcare, Box 967, S-751 09 Uppsala (Sweden); Langstroem, Bengt [Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, S-751 23 Uppsala (Sweden)], E-mail: bengt.langstrom@biorg.uu.se

    2009-05-15

    Introduction: Two- and one-step syntheses of {sup 18}F-labelled analogues of metomidate, such as 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[{sup 18}F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[{sup 18}F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Methods: Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[{sup 18}F]fluoroethyl 4-methylbenzenesulfonate or 3-[{sup 18}F]fluoropropyl 4-methylbenzenesulfonate. These were used as {sup 18}F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. Results: The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46{+-}3% and 79{+-}30%, respectively. Conclusion: Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

  11. Magnetic field perturbation in proton MR imaging - A study of a contrast agent and of distortions due to metallic implants

    International Nuclear Information System (INIS)

    Olsson, M.

    1992-01-01

    Perturbations of the static magnetic field in proton MR imaging (NMR imaging, MRI, MRT) result in image distortion and/or signal loss. An investigation of a superparamagnetic contrast agent for MR imaging has been performed. Magnetite particles were embedded in biodegradable starch spheres with a diameter of one micrometer. Animal experiments showed that the agent was quickly accumulated in the reticulo-endothelial system (RES), causing a decrease in signal intensity in this region. Diffusion within the locally generated magnetic field perturbation is responsible for signal loss in spin-echo images. Furthermore, the magnetic properties of various aneurysm clips were investigated to determine which clips could be used safely in a clinical MR investigation. MR artifacts caused by the metallic clips were studied using a geometric phantom. Non-ferromagnetic clips were concluded to be safe for examinations with medium field (0.3 tesla) MR imaging systems. A comparison study between MR and CT was performed on patients harbouring intracranial, nonferromagnetic aneurysm clips. The artifacts close to the clips were equally serve for MR and CT, but at some distance, the MR images were much less affected than the CT images. Finally, a computer program capable of simulating any realistic MR imaging situation has been developed. Raw data matrices are obtained by solving the Bloch equations. Corrections for intravascular spin behaviour have been implemented together with efficient algorithms. A quantitative investigation of signal displacement and signal loss, caused by small metallic implants, has been performed by computer simulation. An exact expression for the magnetic field outside a homogeneous ellipsoid in an external magnetic field has been derived. Distortions in MR images, caused by perturbing ellipsoids of different shapes and orientations, were studied. (30 refs.) (au)

  12. Hypoxic conditioning as a new therapeutic modality

    Directory of Open Access Journals (Sweden)

    Samuel eVerges

    2015-06-01

    Full Text Available Preconditioning refers to a procedure by which a single noxious stimulus below the threshold of damage is applied to the tissue in order to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic preconditioning relies on complex and active defenses that organisms have developed to counter the adverse consequences of oxygen deprivation. The protection it confers against ischemic attack for instance as well as the underlying biological mechanisms have been extensively investigated in animal models. Based on these data, hypoxic conditioning (consisting in recurrent exposure to hypoxia has been suggested a potential non-pharmacological therapeutic intervention to enhance some physiological functions in individuals in whom acute or chronic pathological events are anticipated or existing. In addition to healthy subjects, some benefits have been reported in patients with cardiovascular and pulmonary diseases as well as in overweight and obese individuals. Hypoxic conditioning consisting in sessions of intermittent exposure to moderate hypoxia repeated over several weeks may induce hematological, vascular, metabolic and neurological effects. This review addresses the existing evidence regarding the use of hypoxic conditioning as a potential therapeutic modality and emphasizes on many remaining issues to clarify and future researches to be performed in the field.

  13. Hypoxic challenge test applied to healthy children

    DEFF Research Database (Denmark)

    Kobbernagel, Helene Elgaard; Nielsen, Kim Gjerum; Hanel, Birgitte

    2013-01-01

    BACKGROUND: Commercial aircraft are pressurised to ~2438 m (8000 ft) above sea level that equates breathing 15% oxygen at sea level. A preflight hypoxic challenge test (HCT) is therefore recommended for children with cystic fibrosis or other chronic lung diseases and inflight oxygen is advised if...

  14. The lifetime of hypoxic human tumor cells

    International Nuclear Information System (INIS)

    Durand, Ralph E.; Sham, Edward

    1998-01-01

    Purpose: For hypoxic and anoxic cells in solid tumors to be a therapeutic problem, they must live long enough to be therapeutically relevant, or else be rapidly recruited into the proliferating compartment during therapy. We have, therefore, estimated lifetime and recruitment rate of hypoxic human tumor cells in multicell spheroids in vitro, or in xenografted tumors in SCID mice. Materials and Methods: Cell turnover was followed by flow cytometry techniques, using antibodies directed at incorporated halogenated pyrimidines. The disappearance of labeled cells was quantified, and verified to be cell loss rather than label dilution. Repopulation was studied in SiHa tumor xenografts during twice-daily 2.5-Gy radiation exposures. Results: The longevity of hypoxic human tumor cells in spheroids or xenografts exceeded that of rodent cell lines, and cell turnover was slower in xenografts than under static growth as spheroids. Human tumor cells remained viable in the hypoxic regions of xenografts for 4-10 days, compared to 3-5 days in spheroids, and 1-3 days for most rodent cells in spheroids. Repopulation was observed within the first few radiation treatments for the SiHa xenografts and, with accumulated doses of more than 10 Gy, virtually all recovered cells had progressed through at least one S-phase. Conclusion: Our results suggest an important difference in the ability of human vs. rodent tumor cells to withstand hypoxia, and raise questions concerning the increased longevity seen in vivo relative to the steady-state spheroid system

  15. Value of an hepatobiliary imaging agent for diagnosing hepatoma. Example of diethyl-IDA

    International Nuclear Information System (INIS)

    Bourguet, P.; Estable, P.; Herry, J.Y.

    1985-01-01

    A comparative study was performed using two hepatic tracers, a Tc 99m labelled colloid and an hepatobiliary agent Tc 99m labelled diethyl-IDA. In some patients with isolated primary hepatocarcinoma the uptake of the hepatobiliary agent was observed but the colloid was not taken up. In the contrary, the hepatobiliary agent has proved to be of limited value for the diagnosis of hepatomas coexisting with cirrhosis and for the detection of secondary hepatocarcinoma [fr

  16. Value of an hepatobiliary imaging agent for diagnosing hepatoma. Example of diethyl-IDA

    Energy Technology Data Exchange (ETDEWEB)

    Bourguet, P; Estable, P; Herry, J Y

    1985-01-01

    A comparative study was performed using two hepatic tracers, a Tc 99m labelled colloid and an hepatobiliary agent Tc 99m labelled diethyl-IDA. In some patients with isolated primary hepatocarcinoma the uptake of the hepatobiliary agent was observed but the colloid was not taken up. In the contrary, the hepatobiliary agent has proved to be of limited value for the diagnosis of hepatomas coexisting with cirrhosis and for the detection of secondary hepatocarcinoma.

  17. Line-scanning confocal microscopy for high-resolution imaging of upconverting rare-earth-based contrast agents

    Science.gov (United States)

    Higgins, Laura M.; Zevon, Margot; Ganapathy, Vidya; Sheng, Yang; Tan, Mei Chee; Riman, Richard E.; Roth, Charles M.; Moghe, Prabhas V.; Pierce, Mark C.

    2015-01-01

    Abstract. Rare-earth (RE) doped nanocomposites emit visible luminescence when illuminated with continuous wave near-infrared light, making them appealing candidates for use as contrast agents in biomedical imaging. However, the emission lifetime of these materials is much longer than the pixel dwell times used in scanning intravital microscopy. To overcome this limitation, we have developed a line-scanning confocal microscope for high-resolution, optically sectioned imaging of samples labeled with RE-based nanomaterials. Instrument performance is quantified using calibrated test objects. NaYF4:Er,Yb nanocomposites are imaged in vitro, and in ex vivo tissue specimens, with direct comparison to point-scanning confocal microscopy. We demonstrate that the extended pixel dwell time of line-scanning confocal microscopy enables subcellular-level imaging of these nanomaterials while maintaining optical sectioning. The line-scanning approach thus enables microscopic imaging of this emerging class of contrast agents for preclinical studies, with the potential to be adapted for real-time in vivo imaging in the clinic. PMID:26603495

  18. Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions

    International Nuclear Information System (INIS)

    Bache, Matthias; Taubert, Helge; Vordermark, Dirk; Zschornak, Martin P; Passin, Sarina; Keßler, Jacqueline; Wichmann, Henri; Kappler, Matthias; Paschke, Reinhard; Kaluđerović, Goran N; Kommera, Harish

    2011-01-01

    Betulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied. In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses. Under normoxic conditions, a half maximal inhibitory concentration (IC 50 ) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The combination of BA with radiotherapy resulted in an additive effect in the U343MG cell line under normoxic and hypoxic conditions. Weak radiation enhancement was observed in U251MG cell line after treatment with BA under normoxic conditions. Furthermore, under hypoxic conditions, the incubation with BA resulted in increased radiation enhancement. The enhancement factor, at an irradiation dose of 15 Gy after treatment with 10 or 15 μM BA, was 2.20 (p = 0.02) and 4.50 (p = 0.03), respectively. Incubation with BA led to decreased cell migration, cleavage of PARP and decreased expression levels of survivin in both cell lines. Additionally, BA treatment resulted in a reduction of HIF-1α protein under hypoxic conditions. Our results suggest that BA is capable

  19. Synthesis and biological evaluation of [18F]tetrafluoroborate: a PET imaging agent for thyroid disease and reporter gene imaging of the sodium/iodide symporter

    International Nuclear Information System (INIS)

    Jauregui-Osoro, Maite; Sunassee, Kavitha; Weeks, Amanda J.; Berry, David J.; Paul, Rowena L.; Cleij, Marcel; O'Doherty, Michael J.; Marsden, Paul K.; Szanda, Istvan; Blower, Philip J.; Banga, Jasvinder Paul; Clarke, Susan E.M.; Ballinger, James R.; Cheng, Sheue-Yann

    2010-01-01

    The human sodium/iodide symporter (hNIS) is a well-established target in thyroid disease and reporter gene imaging using gamma emitters 123 I-iodide, 131 I-iodide and 99m Tc-pertechnetate. However, no PET imaging agent is routinely available. The aim of this study was to prepare and evaluate 18 F-labelled tetrafluoroborate ([ 18 F]TFB) for PET imaging of hNIS. [ 18 F]TFB was prepared by isotopic exchange of BF 4 - with [ 18 F]fluoride in hot hydrochloric acid and purified using an alumina column. Its identity, purity and stability in serum were determined by HPLC, thin-layer chromatography (TLC) and mass spectrometry. Its interaction with NIS was assessed in vitro using FRTL-5 rat thyroid cells, with and without stimulation by thyroid-stimulating hormone (TSH), in the presence and absence of perchlorate. Biodistribution and PET imaging studies were performed using BALB/c mice, with and without perchlorate inhibition. [ 18 F]TFB was readily prepared with specific activity of 10 GBq/mg. It showed rapid accumulation in FRTL-5 cells that was stimulated by TSH and inhibited by perchlorate, and rapid specific accumulation in vivo in thyroid (SUV = 72 after 1 h) and stomach that was inhibited 95% by perchlorate. [ 18 F]TFB is an easily prepared PET imaging agent for rodent NIS and should be evaluated for hNIS PET imaging in humans. (orig.)

  20. A kit prepared technetium-99m agent for cardiac imaging: a preliminary evaluation in dogs

    International Nuclear Information System (INIS)

    Thakur, M.L.

    1982-01-01

    A new 99mTc cardiac agent that can be prepared by a kit method has been developed. The preliminary results in animals indicate that the agent is distributed in the myocardium according to the regional myocardial blood flow and has ability to delineate a myocardial region of infarction

  1. Searching for an alternative oral contrast agent for GI tract MR imaging; in vitro phase, initial report

    International Nuclear Information System (INIS)

    Okla, W.; Szeszkowski, W.; Cieszanowski, A.; Golebiowski, M.

    2002-01-01

    MR has been recently considered to be suitable method for detection GI tract pathologies. A few substances (some of a natural origin) seem to act as an efficient oral MR contrast agents. The aim of this study is to find an alternative substance, which can be administrated orally to patients in order to enhance signal intensity (SI). The ideal agent should have a biphase pattern (high SI in T1 and low in T2), and should be nontoxic and cost effective. Phantom experiments were conducted with 1.5 T MR scanner. T1W and T2W sequences were used for initial estimation. Number of different agents such as: water, Gd-DTPA, barium sulfate, green tea, blueberry juice, cranberry juice, blackcurrant juice, and some more were evaluated. Signal intensity was measured by using elliptical region of interest (ROI). MR imaging in one patient with stomach cancer was also performed. In T1W-FFE sequence cranberry juice reached satisfactorily high signal (SI=1760.14). In T2W-TSE sequence this substance reduced signal intensity (SI=23.10) almost to background level. Blueberry juice appear to be the next substance capable to generate high signal (SI=1558.31) in T1W sequence (T1-TSE). MR examination of a patient with stomach adenocarcinoma (using blueberry juice as an oral contrast agent) satisfactorily depicted and delineated tumor mass on both: T1W and T2W images. Cranberry juice and blueberry juice seemed to act effectively as oral contrast agents for gastrointestinal MR imaging. Thus they need further exploration and trials. (author)

  2. Resistance of hypoxic cells to ionizing radiation is influenced by homologous recombination status

    International Nuclear Information System (INIS)

    Sprong, Debbie; Janssen, Hilde L.; Vens, Conchita; Begg, Adrian C.

    2006-01-01

    Purpose: To determine the role of DNA repair in hypoxic radioresistance. Methods and Materials: Chinese hamster cell lines with mutations in homologous recombination (XRCC2, XRCC3, BRAC2, RAD51C) or nonhomologous end-joining (DNA-PKcs) genes were irradiated under normoxic (20% oxygen) and hypoxic (<0.1% oxygen) conditions, and the oxygen enhancement ratio (OER) was calculated. In addition, Fanconi anemia fibroblasts (complementation groups C and G) were compared with fibroblasts from nonsyndrome patients. RAD51 foci were studied using immunofluorescence. Results: All hamster cell lines deficient in homologous recombination showed a decrease in OER (1.5-2.0 vs. 2.6-3.0 for wild-types). In contrast, the OER for the DNA-PKcs-deficient line was comparable to wild-type controls. The two Fanconi anemia cell strains also showed a significant reduction in OER. The OER for RAD51 foci formation at late times after irradiation was considerably lower than that for survival in wild-type cells. Conclusion: Homologous recombination plays an important role in determining hypoxic cell radiosensitivity. Lower OERs have also been reported in cells deficient in XPF and ERCC1, which, similar to homologous recombination genes, are known to play a role in cross-link repair. Because Fanconi anemia cells are also sensitive to cross-linking agents, this strengthens the notion that the capacity to repair cross-links determines hypoxic radiosensitivity

  3. Dual-purpose linker for alpha helix stabilization and imaging agent conjugation to glucagon-like peptide-1 receptor ligands.

    Science.gov (United States)

    Zhang, Liang; Navaratna, Tejas; Liao, Jianshan; Thurber, Greg M

    2015-02-18

    Peptides display many characteristics of efficient imaging agents such as rapid targeting, fast background clearance, and low non-specific cellular uptake. However, poor stability, low affinity, and loss of binding after labeling often preclude their use in vivo. Using glucagon-like peptide-1 receptor (GLP-1R) ligands exendin and GLP-1 as a model system, we designed a novel α-helix-stabilizing linker to simultaneously address these limitations. The stabilized and labeled peptides showed an increase in helicity, improved protease resistance, negligible loss or an improvement in binding affinity, and excellent in vivo targeting. The ease of incorporating azidohomoalanine in peptides and efficient reaction with the dialkyne linker enable this technique to potentially be used as a general method for labeling α helices. This strategy should be useful for imaging beta cells in diabetes research and in developing and testing other peptide targeting agents.

  4. Primary evaluation of a nickel-chlorophyll derivative as a multimodality agent for tumor imaging and photodynamic therapy

    International Nuclear Information System (INIS)

    Ozge Er; Fatma Yurt Lambrecht; Kasim Ocakoglu; Cagla Kayabasi; Cumhur Gunduz

    2015-01-01

    In this study, the biological potential of a nickel chlorophyll derivative (Ni-PH-A) as a multimodal agent for tumor imaging and photodynamic therapy (PDT) was investigated. Optimum conditions of labeling with 131 I were investigated and determined as pH 10 and 1 mg amount of iodogen. Biodistribution results of 131 I labeled Ni-PH-A in female rats indicated that radiolabeled Ni-PH-A maximum uptake in the liver, spleen and ovary was observed at 30 min. Intercellular uptake and PDT efficacy of Ni-PH-A were better in MDAH-2774 (human ovarian endometrioid adenocarcinoma) than in MCF-7 (human breast adenocarcinoma) cells. Ni-PH-A might be a promising multimodal agent for lung, ovary and liver tumor imaging and PDT. (author)

  5. The Impact of “Omic” and Imaging Technologies on Assessing the Host Immune Response to Biodefence Agents

    Directory of Open Access Journals (Sweden)

    Julia A. Tree

    2014-01-01

    Full Text Available Understanding the interactions between host and pathogen is important for the development and assessment of medical countermeasures to infectious agents, including potential biodefence pathogens such as Bacillus anthracis, Ebola virus, and Francisella tularensis. This review focuses on technological advances which allow this interaction to be studied in much greater detail. Namely, the use of “omic” technologies (next generation sequencing, DNA, and protein microarrays for dissecting the underlying host response to infection at the molecular level; optical imaging techniques (flow cytometry and fluorescence microscopy for assessing cellular responses to infection; and biophotonic imaging for visualising the infectious disease process. All of these technologies hold great promise for important breakthroughs in the rational development of vaccines and therapeutics for biodefence agents.

  6. Highly stable polymer coated nano-clustered silver plates: a multimodal optical contrast agent for biomedical imaging

    International Nuclear Information System (INIS)

    Ray, Aniruddha; Mukundan, Ananya; Karamchand, Leshern; Kopelman, Raoul; Xie, Zhixing; Wang, Xueding

    2014-01-01

    Here, we present a new optical contrast agent based on silver nanoplate clusters embedded inside of a polymer nano matrix. Unlike nanosphere clusters, which have been well studied, nanoplate clusters have unique properties due to the different possible orientations of interaction between the individual plates, resulting in a significant broadening of the absorption spectra. These nanoclusters were immobilized inside of a polymer cladding so as to maintain their stability and optical properties under in vivo conditions. The polymer-coated silver nanoplate clusters show a lower toxicity compared to the uncoated nanoparticles. At high nanoparticle concentrations, cell death occurs mostly due to apoptosis. These nanoparticles were used for targeted fluorescence imaging in a rat glioma cell line by incorporating a fluorescent dye into the matrix, followed by conjugation of a tumor targeting an F3 peptide. We further used these nanoparticles as photoacoustic contrast agents in vivo to enhance the contrast of the vasculature structures in a rat ear model. We observed a contrast enhancement of over 90% following the nanoparticle injection. It is also shown that these NPs can serve as efficient contrast agents, with specific targeting abilities for broadband multimodal imaging that are usable for diagnostic applications and that extend into use as therapeutic agents as well. (paper)

  7. Mechanical and dynamic characteristics of encapsulated microbubbles coupled by magnetic nanoparticles as multifunctional imaging and drug delivery agents

    Science.gov (United States)

    Guo, Gepu; Lu, Lu; Yin, Leilei; Tu, Juan; Guo, Xiasheng; Wu, Junru; Xu, Di; Zhang, Dong

    2014-11-01

    Development of magnetic encapsulated microbubble agents that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology and one which will have far-reaching impact on medical diagnosis and therapies. However, properly designing multifunctional agents that can satisfy particular diagnostic/therapeutic requirements has been recognized as rather challenging, because there is a lack of comprehensive understanding of how the integration of magnetic nanoparticles to microbubble encapsulating shells affects their mechanical properties and dynamic performance in ultrasound imaging and drug delivery. Here, a multifunctional imaging contrast and in-situ gene/drug delivery agent was synthesized by coupling super paramagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles. Systematical studies were performed to investigate the SPIO-concentration-dependence of microbubble mechanical properties, acoustic scattering response, inertial cavitation activity and ultrasound-facilitated gene transfection effect. These demonstrated that, with the increasing SPIO concentration, the microbubble mean diameter and shell stiffness increased and ultrasound scattering response and inertial cavitation activity could be significantly enhanced. However, an optimized ultrasound-facilitated vascular endothelial growth factor transfection outcome would be achieved by adopting magnetic albumin-shelled microbubbles with an appropriate SPIO concentration of 114.7 µg ml-1. The current results would provide helpful guidance for future development of multifunctional agents and further optimization of their diagnostic/therapeutic performance in clinic.

  8. Mechanical and dynamic characteristics of encapsulated microbubbles coupled by magnetic nanoparticles as multifunctional imaging and drug delivery agents

    International Nuclear Information System (INIS)

    Guo, Gepu; Lu, Lu; Tu, Juan; Guo, Xiasheng; Zhang, Dong; Yin, Leilei; Wu, Junru; Xu, Di

    2014-01-01

    Development of magnetic encapsulated microbubble agents that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology and one which will have far-reaching impact on medical diagnosis and therapies. However, properly designing multifunctional agents that can satisfy particular diagnostic/therapeutic requirements has been recognized as rather challenging, because there is a lack of comprehensive understanding of how the integration of magnetic nanoparticles to microbubble encapsulating shells affects their mechanical properties and dynamic performance in ultrasound imaging and drug delivery. Here, a multifunctional imaging contrast and in-situ gene/drug delivery agent was synthesized by coupling super paramagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles. Systematical studies were performed to investigate the SPIO-concentration-dependence of microbubble mechanical properties, acoustic scattering response, inertial cavitation activity and ultrasound-facilitated gene transfection effect. These demonstrated that, with the increasing SPIO concentration, the microbubble mean diameter and shell stiffness increased and ultrasound scattering response and inertial cavitation activity could be significantly enhanced. However, an optimized ultrasound-facilitated vascular endothelial growth factor transfection outcome would be achieved by adopting magnetic albumin-shelled microbubbles with an appropriate SPIO concentration of 114.7 µg ml −1 . The current results would provide helpful guidance for future development of multifunctional agents and further optimization of their diagnostic/therapeutic performance in clinic. (paper)

  9. Utility decay rates of T1-weighted magnetic resonance imaging contrast based on redox-sensitive paramagnetic nitroxyl contrast agents

    International Nuclear Information System (INIS)

    Matsumoto, Ken-ichiro

    2009-01-01

    The availability and applicability of the combination of paramagnetic nitroxyl contrast agent and T 1 -weighted gradient echo (GE)-based dynamic magnetic resonance imaging (MRI) measurement for redox imaging are described. The time courses of T 1 -weighted GE MRI signal intensities according to first-order paramagnetic loss of a nitroxyl contrast agent were simulated for several experimental conditions. The apparent decay rate calculated based on decreasing T 1 -weighted MRI contrast (k MRI ) can show an approximate value of the original decay rate (k true ) discretionarily given for simulation with suitable experimental parameters. The difference between k MRI and k true can be sufficiently small under T 1 -weighted spoiled gradient echo (SPGR) scan conditions (repetition time=75 ms, echo time=3 ms, and flip angle=45deg), with a conventional redox-sensitive nitroxyl contrast agent, such as 4-hydroxy-2,2,6,6,-tetramethylpiperidine-N-oxyl (TEMPOL) and/or 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (carbamoyl-PROXYL), and with intravenous (i.v.) doses of below 1.5 γmol/g body weight (b.w.) for mice. The results of this simulation suggest that the k MRI of nitroxyl contrast agents can be the primary index of redox status under biological conditions. (author)

  10. Seizure Severity Is Correlated With Severity of Hypoxic-Ischemic Injury in Abusive Head Trauma.

    Science.gov (United States)

    Dingman, Andra L; Stence, Nicholas V; O'Neill, Brent R; Sillau, Stefan H; Chapman, Kevin E

    2017-12-12

    The objective of this study was to characterize hypoxic-ischemic injury and seizures in abusive head trauma. We performed a retrospective study of 58 children with moderate or severe traumatic brain injury due to abusive head trauma. Continuous electroencephalograms and magnetic resonance images were scored. Electrographic seizures (51.2%) and hypoxic-ischemic injury (77.4%) were common in our cohort. Younger age was associated with electrographic seizures (no seizures: median age 13.5 months, interquartile range five to 25 months, versus seizures: 4.5 months, interquartile range 3 to 9.5 months; P = 0.001). Severity of hypoxic-ischemic injury was also associated with seizures (no seizures: median injury score 1.0, interquartile range 0 to 3, versus seizures: 4.5, interquartile range 3 to 8; P = 0.01), but traumatic injury severity was not associated with seizures (no seizures: mean injury score 3.78 ± 1.68 versus seizures: mean injury score 3.83 ± 0.95, P = 0.89). There was a correlation between hypoxic-ischemic injury severity and seizure burden when controlling for patient age (r s =0.61, P interquartile range 0 to 0.23 on magnetic resonance imaging done within two days versus median restricted diffusion ratio 0.13, interquartile range 0.01 to 0.43 on magnetic resonance imaging done after two days, P = 0.03). Electrographic seizures are common in children with moderate to severe traumatic brain injury from abusive head trauma, and therefore children with suspected abusive head trauma should be monitored with continuous electroencephalogram. Severity of hypoxic-ischemic brain injury is correlated with severity of seizures, and evidence of hypoxic-ischemic injury on magnetic resonance imaging may evolve over time. Therefore children with a high seizure burden should be reimaged to evaluate for evolving hypoxic-ischemic injury. Published by Elsevier Inc.

  11. Low-Cost, High-Throughput 3-D Pulmonary Imager Using Hyperpolarized Contrast Agents and Low-Field MRI

    Science.gov (United States)

    2017-10-01

    low- cost and high-throughput was a key element proposed for this project, which we believe will be of significant benefit to the patients suffering...Award Number: W81XWH-15-1-0272 TITLE: Low- Cost , High-Throughput 3-D Pulmonary Imager Using Hyperpolarized Contrast Agents and Low-Field MRI...STATEMENT: Approved for Public Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s

  12. Low Cost, High-Throughput 3-D Pulmonary Imager Using Hyperpolarized Contrast Agents and Low-Field MRI

    Science.gov (United States)

    2017-10-01

    greater gas polarizations and production amounts/ throughputs- benefiting in particular from the advent of com- pact, high-power, relatively low- cost ...Award Number: W81XWH-15-1-0271 TITLE: Low- Cost , High-Throughput 3-D Pulmonary Imager Using Hyperpolarized Contrast Agents and Low-Field MRI...DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the

  13. Development of Gd(III) porphyrin-conjugated chitosan nanoparticles as contrast agents for magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Jahanbin, Tania [Université Paul Sabatier, Toulouse III, INSERM U825, CHU Purpan, 31059 Toulouse Cedex 9 (France); Sauriat-Dorizon, Hélène [Institut de Chimie Moléculaire et des Matériaux d' Orsay, UMR CNRS 8182, ECBB, Université Paris-Sud, 91405 Orsay (France); Spearman, Peter [Faculty of Science, Engineering and Computing, University of Kingston, Penrhyn Road Kingston upon Thames Surrey KT1 2EE, London (United Kingdom); Benderbous, Soraya, E-mail: soraya.benderbous@univ-tlse3.fr [Université Paul Sabatier, Toulouse III, INSERM U825, CHU Purpan, 31059 Toulouse Cedex 9 (France); Korri-Youssoufi, Hafsa, E-mail: hafsa.korri-youssoufi@u-psud.fr [Institut de Chimie Moléculaire et des Matériaux d' Orsay, UMR CNRS 8182, ECBB, Université Paris-Sud, 91405 Orsay (France)

    2015-07-01

    A novel magnetic resonance imaging (MRI) contrast agent based on gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] conjugated with chitosan nanoparticles has been developed. The chitosan nanoparticles were synthesized following an ionic gelation method and the conditions optimized to generate small nanoparticles (CNs) with a narrow size distribution of 35–65 nm. The gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] was loaded into chitosan nanoparticles by passive adsorption. The interaction of chitosan with Gd(TPyP) has been examined by UV–visible, Fourier transform infrared spectroscopies (FT-IR) and inductively coupled plasma mass spectrometry (ICP-MS), which indicate the successful association of Gd(TPyP) without any structural distortion throughout the chitosan nanoparticles. The potential of Gd(TPyP)-CNs as MRI contrast agent has been investigated by magnetic resonance imaging (MRI) in-vitro. Relaxivities of Gd(TPyP)-CNs obtained from T{sub 1}-weighted images, increased with Gd concentration and attained an optimum r{sub 1} of 38.35 mM{sup −1} s{sup −1}, which is 12-fold higher compared to commercial Gd-DOTA (~ 4 mM{sup −1} s{sup −1} at 3T). The combination of such strong MRI contrast with the known properties of porphyrins in photodynamic therapy and biocompatibility of chitosan, presents a new perspective in using these compounds in cancer theranostics. - Highlights: • Synthesis of chitosan nanoparticles with small size • Study of loading properties with gadolinium porphyrins • In vitro properties of the conjugated complex as contrast agent for MRI imaging • Comparison of MRI properties with commercial contrast agent Gd-DOTA.

  14. Hyperthermia and chemotherapy agent

    International Nuclear Information System (INIS)

    Roizin-Towle, L.; Hall, E.J.

    1981-01-01

    The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

  15. Imaging of vaporised sub-micron phase change contrast agents with high frame rate ultrasound and optics

    Science.gov (United States)

    Lin, Shengtao; Zhang, Ge; Jamburidze, Akaki; Chee, Melisse; Hau Leow, Chee; Garbin, Valeria; Tang, Meng-Xing

    2018-03-01

    Phase-change ultrasound contrast agent (PCCA), or nanodroplet, shows promise as an alternative to the conventional microbubble agent over a wide range of diagnostic applications. Meanwhile, high-frame-rate (HFR) ultrasound imaging with microbubbles enables unprecedented temporal resolution compared to traditional contrast-enhanced ultrasound imaging. The combination of HFR ultrasound imaging and PCCAs can offer the opportunity to observe and better understand PCCA behaviour after vaporisation captures the fast phenomenon at a high temporal resolution. In this study, we utilised HFR ultrasound at frame rates in the kilohertz range (5-20 kHz) to image native and size-selected PCCA populations immediately after vaporisation in vitro within clinical acoustic parameters. The size-selected PCCAs through filtration are shown to preserve a sub-micron-sized (mean diameter  1 µm) that originate from native PCCA emulsion. The results demonstrate imaging signals with different amplitudes and temporal features compared to that of microbubbles. Compared with the microbubbles, both the B-mode and pulse-inversion (PI) signals from the vaporised PCCA populations were reduced significantly in the first tens of milliseconds, while only the B-mode signals from the PCCAs were recovered during the next 400 ms, suggesting significant changes to the size distribution of the PCCAs after vaporisation. It is also shown that such recovery in signal over time is not evident when using size-selective PCCAs. Furthermore, it was found that signals from the vaporised PCCA populations are affected by the amplitude and frame rate of the HFR ultrasound imaging. Using high-speed optical camera observation (30 kHz), we observed a change in particle size in the vaporised PCCA populations exposed to the HFR ultrasound imaging pulses. These findings can further the understanding of PCCA behaviour under HFR ultrasound imaging.

  16. Curved reformat of the paediatric brain MRI into a 'flat-earth map' - standardised method for demonstrating cortical surface atrophy resulting from hypoxic-ischaemic encephalopathy.

    Science.gov (United States)

    Simpson, Ewan; Andronikou, Savvas; Vedajallam, Schadie; Chacko, Anith; Thai, Ngoc Jade

    2016-09-01

    Hypoxic-ischaemic encephalopathy is optimally imaged with brain MRI in the neonatal period. However neuroimaging is often also performed later in childhood (e.g., when parents seek compensation in cases of alleged birth asphyxia). We describe a standardised technique for creating two curved reconstructions of the cortical surface to show the characteristic surface changes of hypoxic-ischaemic encephalopathy in children imaged after the neonatal period. The technique was applied for 10 cases of hypoxic-ischaemic encephalopathy and also for age-matched healthy children to assess the visibility of characteristic features of hypoxic-ischaemic encephalopathy. In the abnormal brains, fissural or sulcal widening was seen in all cases and ulegyria was identifiable in 7/10. These images could be used as a visual aid for communicating MRI findings to clinicians and other interested parties.

  17. STTARR: a radiation treatment and multi-modal imaging facility for fast tracking novel agent development in small animal models

    International Nuclear Information System (INIS)

    Yeung, Ivan; McKee, Trevor; Jaffray, David; Hill, Richard

    2014-01-01

    Small animal models play a pivotal role in the pipeline development of novel agents and strategies in personalized cancer therapy. The Spatio-Temporal Targeting and Amplification of Radiation Response Program (STTARR) consists of an animal imaging and precision radiation facility designed to provide innovative biologic imaging and targeted radiation treatment strategies in small animals. The design is to mirror the imaging and radiation treatment facility in a modern cancer center. The STTARR features imaging equipment of small animal scale including CT, MRI, PET, SPECT, Optical devices as well as image guided irradiators. The fleet of imaging and irradiation equipment provides a platform for identification of biological targets of the specific molecular pathways that influence both tumor progression and a patient's response to radiation therapy. Examples will be given in the utilization of the imaging facilities for development in novel approaches in cancer therapy including a PET-FAZA study for hypoxia measurement in a pancreatic adenocarcinoma xenograft model. In addition, the cone-beam image guided small animal irradiator developed at our institute will also be described. The animal platform (couch) provides motion in 3 dimensions to position the animal to the isocentre of the beam. A pair of rotational arms supporting the X-ray/detector pair enables acquisition of cone-beam images of the animal which give rise to image guided precision of 0.5 mm. The irradiation energy ranges from 50 to 225 kVp at a dose rate from 10-400 cGy/min. The gantry is able to direct X-ray beam of different directions to give conformal radiation treatment to the animal. A dedicated treatment planning system is able to perform treatment planning and provide commonly used clinical metrics in the animal treatment plan. Examples will be given to highlight the use of the image guided irradiator for research of drug/irradiation regimen in animal models. (author)

  18. PLGA nanoparticles from nano-emulsion templating as imaging agents: Versatile technology to obtain nanoparticles loaded with fluorescent dyes.

    Science.gov (United States)

    Fornaguera, C; Feiner-Gracia, N; Calderó, G; García-Celma, M J; Solans, C

    2016-11-01

    The interest in polymeric nanoparticles as imaging systems for biomedical applications has increased notably in the last decades. In this work, PLGA nanoparticles, prepared from nano-emulsion templating, have been used to prepare novel fluorescent imaging agents. Two model fluorescent dyes were chosen and dissolved in the oil phase of the nano-emulsions together with PLGA. Nano-emulsions were prepared by the phase inversion composition (PIC) low-energy method. Fluorescent dye-loaded nanoparticles were obtained by solvent evaporation of nano-emulsion templates. PLGA nanoparticles loaded with the fluorescent dyes showed hydrodynamic radii lower than 40nm; markedly lower than those reported in previous studies. The small nanoparticle size was attributed to the nano-emulsification strategy used. PLGA nanoparticles showed negative surface charge and enough stability to be used for biomedical imaging purposes. Encapsulation efficiencies were higher than 99%, which was also attributed to the nano-emulsification approach as well as to the low solubility of the dyes in the aqueous component. Release kinetics of both fluorescent dyes from the nanoparticle dispersions was pH-independent and sustained. These results indicate that the dyes could remain encapsulated enough time to reach any organ and that the decrease of the pH produced during cell internalization by the endocytic route would not affect their release. Therefore, it can be assumed that these nanoparticles are appropriate as systemic imaging agents. In addition, in vitro toxicity tests showed that nanoparticles are non-cytotoxic. Consequently, it can be concluded that the preparation of PLGA nanoparticles from nano-emulsion templating represents a very versatile technology that enables obtaining biocompatible, biodegradable and safe imaging agents suitable for biomedical purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. An MR Contrast Agent for Intra-Prostatic Imaging of Prostatic Cancer

    National Research Council Canada - National Science Library

    Josephson, Lee

    2004-01-01

    The goal of the current research is the development of a magnetic nanoparticle based MR contrast agent that binds the gastrin releasing peptide receptor, a molecular marker associated with neoplasia...

  20. An MR Contrast Agent for Intra-Prostatic Imaging of Prostatic Cancer

    National Research Council Canada - National Science Library

    Josephson, Lee

    2005-01-01

    An MR contrast agent targeted to the GRP receptor will be a novel pharmaceutical capable of non-invasively, and at high spatial resolution, characterizing healthy and patholological regions within the prostate...

  1. Biologically inspired autonomous agent navigation using an integrated polarization analyzing CMOS image sensor

    NARCIS (Netherlands)

    Sarkaer, M.; San Segundo Bello, D.; Van Hoof, C.; Theuwissen, A.

    2010-01-01

    The navigational strategies of insects using skylight polarization are interesting for applications in autonomous agent navigation because they rely on very little information for navigation. A polarization navigation sensor using the Stokes parameters to determine the orientation is presented. The

  2. Fabrication and imaging study of ultrasound/fluorescence bi-modal contrast agent based on polymeric microbubbles

    International Nuclear Information System (INIS)

    Xing Zhanwen; Ke Hengte; Wang Jinrui; Zhao Bo; Qu Enze; Yue Xiuli; Dai Zhifei

    2013-01-01

    Objective: To fabricate an ultrasound/fluorescence bi-modal contrast agent by encapsulating fluorescent quantum dots into polymeric ultrasound contrast agent microbubbles. Methods: Polylactic acid (PLA, 500 mg), (1R)-(+)-camphor (50 mg) and CdSe/ZnS quantum dots (0.5 ml, 2.3 μmol/L)were dissolved or dispersed in dichloromethane (10 ml) to form in an organic phase. Ammonium carbonate solution and poly (vinyl alcohol) solution were employed as the internal and external water phase, respectively. The fluorescent microbubbles were generated using double emulsion solvent evaporation and lyophilization methods. The morphology and illumination were characterized by scanning electron microscopy (SEM) and fluorescence spectrophotometry. Synchronized contrast-enhanced ultrasound and fluorescence imaging was acquired by injecting fluorescent microbubbles into the silicone tube coupled to a self-made ultrasound/fluorescence imaging device. Ultrasound/fluorescence bi-modal in vivo imaging was acquired on the kidney of New Zealand rabbits and suckling mice. Results: The fluorescent microbubbles were hollow spheres with an averaged diameter of (1.62 ± 1.47) μm. More than 99% of these microbubbles were less than 8 μm in diameter, which met the size criteria for ultrasound contrast agents. The fluorescence emission peak of the microbubbles appeared at 632 nm, indicating that good luminescence properties of quantum dots were maintained. In vitro ultrasound/fluorescence imaging showed no echoic signal when the silicone tube was filled with saline, but there was a strong echo when filled with fluorescent microbubbles. The liquid column with fluorescent microbubbles emitted red luminescence under ultraviolet irradiation. The kidney of the rabbit was remarkably enhanced after the administration of fluorescent microbubbles. Bright fluorescence could be observed at the injection site of the suckling mice via subcutaneous injection. Conclusions: A bi-modal but single contrast agent

  3. Activation of radiosensitizers by hypoxic cells

    International Nuclear Information System (INIS)

    Olive, P.L.; Durand, R.E.

    1978-01-01

    Hypoxic cells metabolize nitroheterocyclic compounds to produce toxic intermediates capable of affecting the survival of neighboring oxygenated cells. Mutagenesis experiments with E. coli WP-2 343 (deficient in nitro-reductase) indicated that reduction of nitroheterocyclics outside bacteria causes killing and mutations within bacteria, presumably due to the transfer of the 'active' specie(s). Using animal tissue slices to reduce nitrofurans, cultured L-929 cells incubated under aerobic conditions were far more sensitive to the toxic and DNA damaging effects of these drugs. Transfer of the active species also occurs in a tissue-like environment in multicell spheroids where the presence of a hypoxic central core served to convert the nitroheterocyclics to intermediates which also damaged the neighbouring oxygenated cells. (author)

  4. Activation of radiosensitizers by hypoxic cells

    Energy Technology Data Exchange (ETDEWEB)

    Olive, P L; Durand, R E [Wisconsin Clinical Cancer Center, Madison (USA). Dept. of Human Oncology

    1978-06-01

    Hypoxic cells metabolize nitroheterocyclic compounds to produce toxic intermediates capable of affecting the survival of neighboring oxygenated cells. Mutagenesis experiments with E. coli WP-2 343 (deficient in nitro-reductase) indicated that reduction of nitroheterocyclics outside bacteria causes killing and mutations within bacteria, presumably due to the transfer of the 'active' specie(s). Using animal tissue slices to reduce nitrofurans, cultured L-929 cells incubated under aerobic conditions were far more sensitive to the toxic and DNA damaging effects of these drugs. Transfer of the active species also occurs in a tissue-like environment in multicell spheroids where the presence of a hypoxic central core served to convert the nitroheterocyclics to intermediates which also damaged the neighbouring oxygenated cells.

  5. Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast Agent in Companion Dogs with Naturally Occurring Cancer.

    Science.gov (United States)

    Ghaghada, Ketan B; Sato, Amy F; Starosolski, Zbigniew A; Berg, John; Vail, David M

    2016-01-01

    Companion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography (CT) imaging of solid tumors in companion dogs with naturally occurring cancer. The institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years) with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study. Liposomal-I resulted in significant (p contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan. The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small and large tumors in companion dogs with naturally occurring cancer. The study warrants future work to assess the sensitivity and specificity of the Liposomal-I agent in various types of

  6. In vitro and in vivo evaluation of [123I]IBZM: a potential CNS D-2 dopamine receptor imaging agent

    International Nuclear Information System (INIS)

    Kung, H.F.; Pan, S.; Kung, M.P.; Billings, J.; Kasliwal, R.; Reilley, J.; Alavi, A.

    1989-01-01

    In vitro binding characteristics of a CNS dopamine D-2 receptor imaging agent, (S)-N-[(1-ethyl-2-pyrrolidinyl)] methyl-2-hydroxy-3-iodo-6-methoxybenzamide [( 125 I]IBZM), was carried out in rats. Also brain images, as well as organ biodistribution were determined in a monkey following the administration of 123 I-labeled compound. The S-(-)-I[ 125 I]IBZM showed high specific dopamine D-2 receptor binding in rat striatum (Kd = 0.426 +/- 0.082 nM, Bmax = 480 +/- 22 fmol/mg of protein). Competition of various ligands for the IBZM binding displayed the following rank order of potency: spiperone greater than S(-)IBZM much greater than R(+)IBZM greater than or equal to S(-)BZM greater than dopamine greater than ketanserin greater than SCH-23390 much greater than propranolol, norepinephrine, serotonin. In vivo planar images of a monkey injected with [ 123 I]IBZM demonstrated a high concentration in basal ganglia of brain. The ratios of activity in the basal ganglia to cerebellum and the cortex to cerebellum in monkey brain were 4.93 and 1.44, respectively, at 120 min postinjection. These preliminary results indicate that [ 123 I]IBZM is a potentially promising imaging agent for the investigation of dopamine D-2 receptors in humans

  7. Acute kidney injury with hypoxic respiratory failure

    OpenAIRE

    Neubert, Zachary; Hoffmann, Paul; Owshalimpur, David

    2014-01-01

    A 27-year-old Caucasian man was transferred from a remote clinic with acute kidney injury for the prior 7–10 days preceded by gastroenteritis. His kidney biopsy showed non-specific mesangiopathic glomerular changes, minimal tubulointerstitial disease without sclerosis, crescents, nor evidence of vasculitis. On his third hospital day, he developed acute hypoxic respiratory failure requiring intubation and mechanical ventilation. Pulmonary renal syndromes ranked highest on his differential diag...

  8. Hypoxic human cancer cells are sensitized to BH-3 mimetic–induced apoptosis via downregulation of the Bcl-2 protein Mcl-1

    Science.gov (United States)

    Harrison, Luke R.E.; Micha, Dimitra; Brandenburg, Martin; Simpson, Kathryn L.; Morrow, Christopher J.; Denneny, Olive; Hodgkinson, Cassandra; Yunus, Zaira; Dempsey, Clare; Roberts, Darren; Blackhall, Fiona; Makin, Guy; Dive, Caroline

    2011-01-01

    Solid tumors contain hypoxic regions in which cancer cells are often resistant to chemotherapy-induced apoptotic cell death. Therapeutic strategies that specifically target hypoxic cells and promote apoptosis are particularly appealing, as few normal tissues experience hypoxia. We have found that the compound ABT-737, a Bcl-2 homology domain 3 (BH-3) mimetic, promotes apoptotic cell death in human colorectal carcinoma and small cell lung cancer cell lines exposed to hypoxia. This hypoxic induction of apoptosis was mediated through downregulation of myeloid cell leukemia sequence 1 (Mcl-1), a Bcl-2 family protein that serves as a biomarker for ABT-737 resistance. Downregulation of Mcl-1 in hypoxia was independent of hypoxia-inducible factor 1 (HIF-1) activity and was consistent with decreased global protein translation. In addition, ABT-737 induced apoptosis deep within tumor spheroids, consistent with an optimal hypoxic oxygen tension being necessary to promote ABT-737–induced cell death. Tumor xenografts in ABT-737–treated mice also displayed significantly more apoptotic cells within hypoxic regions relative to normoxic regions. Synergies between ABT-737 and other cytotoxic drugs were maintained in hypoxia, suggesting that this drug may be useful in combination with chemotherapeutic agents. Taken together, these findings suggest that Mcl-1–sparing BH-3 mimetics may induce apoptosis in hypoxic tumor cells that are resistant to other chemotherapeutic agents and may have a role in combinatorial chemotherapeutic regimens for treatment of solid tumors. PMID:21393866

  9. Synthesis and evaluation of novel Tc-99m labeled NGR-containing hexapeptides as tumor imaging agents.

    Science.gov (United States)

    Kim, Dae-Weung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Kim, Chang Guhn

    2015-02-01

    Asparagine-glycine-arginine (NGR)-containing peptides targeting aminopeptidase N (APN)/CD13 can be an excellent candidate for targeting ligands in molecular tumor imaging. In this study, we developed two NGR-containing hexapeptides, and evaluated the diagnostic performance of Tc-99m labeled hexapeptides as molecular imaging agents in an HT-1080 fibrosarcoma-bearing murine model. Peptides were synthesized using Fmoc solid-phase peptide synthesis. Radiochemical purity of Tc-99m was evaluated using instant thin-layer chromatography. The uptake of two NGR-containing hexapeptides within HT-1080 cells was evaluated in vitro. In HT-1080 fibrosarcoma tumor-bearing mice, gamma images were acquired. A biodistribution study was performed to calculate percentage of the injected dose per gram of tissue (%ID/g). Two hexapeptides, glutamic acid-cysteine-glycine (ECG)-NGR and NGR-ECG were successfully synthesized. After radiolabeling procedures with Tc-99m, the complexes Tc-99m hexapeptides were prepared in high yield. The uptake of Tc-99m ECG-NGR within the tumor cells had been assured by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-NGR was accumulated substantially in the subcutaneously engrafted tumor. However, Tc-99m NGR-ECG was accumulated minimally in the tumor. Two NGR-containing hexapeptides, ECG-NGR and NGR-ECG were developed as molecular imaging agents to target APN/CD13 in HT-1080 fibrosarcoma. Tc-99m ECG-NGR showed a significant uptake in the tumor, and it is a good candidate for tumor imaging. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Increased transverse relaxivity in ultrasmall superparamagnetic iron oxide nanoparticles used as MRI contrast agent for biomedical imaging.

    Science.gov (United States)

    Mishra, Sushanta Kumar; Kumar, B S Hemanth; Khushu, Subash; Tripathi, Rajendra P; Gangenahalli, Gurudutta

    2016-09-01

    Synthesis of a contrast agent for biomedical imaging is of great interest where magnetic nanoparticles are concerned, because of the strong influence of particle size on transverse relaxivity. In the present study, biocompatible magnetic iron oxide nanoparticles were synthesized by co-precipitation of Fe 2+ and Fe 3+ salts, followed by surface adsorption with reduced dextran. The synthesized nanoparticles were spherical in shape, and 12 ± 2 nm in size as measured using transmission electron microscopy; this was corroborated with results from X-ray diffraction and dynamic light scattering studies. The nanoparticles exhibited superparamagnetic behavior, superior T 2 relaxation rate and high relaxivities (r 1  = 18.4 ± 0.3, r 2  = 90.5 ± 0.8 s -1 mM -1 , at 7 T). MR image analysis of animals before and after magnetic nanoparticle administration revealed that the signal intensity of tumor imaging, specific organ imaging and whole body imaging can be clearly distinguished, due to the strong relaxation properties of these nanoparticles. Very low concentrations (3.0 mg Fe/kg body weight) of iron oxides are sufficient for early detection of tumors, and also have a clear distinction in pre- and post-enhancement of contrast in organs and body imaging. Many investigators have demonstrated high relaxivities of magnetic nanoparticles at superparamagnetic iron oxide level above 50 nm, but this investigation presents a satisfactory, ultrasmall, superparamagnetic and high transverse relaxivity negative contrast agent for diagnosis in pre-clinical studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Synthesis, characterization and identification of the hexakis (trimethylphosphite) [Tc-99m]technetium(I) cation as a myocardial imaging agent

    International Nuclear Information System (INIS)

    Dean, R.T.; Adams, M.D.; Miller, F.W.; Robbins, M.S.; Wester, D.W.; White, D.H.

    1984-01-01

    Hexakis(trimethylphosphite)[Tc-99m]technetium(I), a monocationic complex, was synthesized for evaluation as a myocardial imaging agent. The above product was synthesized by reacting a methanolic solution of NaTcO/sub 4/ with trimethyl phosphite in an inert atmosphere at 100 0 for 30 min. Using the Tc-99 isotope, mg quantities were isolated for full characterization by precipitation from the reaction mixture using sodium tetraphenylborate. Recrystallization from methanol gave crystals of the tetraphenylborate salt. Elemental analyses, Tc-99 and P-31 NMR, mass spectra, X-ray photoelectron spectra, ir and X-ray crystal structure were all consistent with a hexacoordinate octahedral structure of the proposed monocation. The products formed from the Tc-99 isotope and the Tc-99m isotope were shown to be identical by HPLC using simultaneous radiometric and UV detection. The myocardial imaging properties of the title compound were evaluated by rat biodistribution and dog imaging. Five minutes after intravenous administration in rats, 3% dose/gm was in the heart with tissue ratios of heart/blood of 30, heart/liver of 4, heart/lung of 2. These compare to T1-201 values of 6% dose/gm in the heart with tissue ratios of heart/blood of 24, heart/liver of 6, heart/lung of 1. Imaging in an anesthetized dog revealed excellent myocardial uptake with persistent images through a 60 minute period. From these data the hexakis(trimethylphosphite)[Tc-99m]technetium(I) cation was identified as a myocardial imaging agent suitable for further evaluation

  12. Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging

    Directory of Open Access Journals (Sweden)

    Justin J. Tse

    2017-01-01

    Full Text Available Micro-computed tomography (micro-CT facilitates the visualization and quantification of contrast-enhanced microvessels within intact tissue specimens, but conventional preclinical vascular contrast agents may be inadequate near dense tissue (such as bone. Typical lead-based contrast agents do not exhibit optimal X-ray absorption properties when used with X-ray tube potentials below 90 kilo-electron volts (keV. We have developed a high-atomic number lanthanide (erbium contrast agent, with a K-edge at 57.5 keV. This approach optimizes X-ray absorption in the output spectral band of conventional microfocal spot X-ray tubes. Erbium oxide nanoparticles (nominal diameter 4000 Hounsfield units, and perfusion of vessels < 10 μm in diameter was demonstrated in kidney glomeruli. The described new contrast agent facilitated the visualization and quantification of vessel density and microarchitecture, even adjacent to dense bone. Erbium’s K-edge makes this contrast agent ideally suited for both single- and dual-energy micro-CT, expanding potential preclinical research applications in models of musculoskeletal, oncological, cardiovascular, and neurovascular diseases.

  13. Synthesis and Preclinical Characterization of a Cationic Iodinated Imaging Contrast Agent (CA4+) and Its Use for Quantitative Computed Tomography of Ex Vivo Human Hip Cartilage.

    Science.gov (United States)

    Stewart, Rachel C; Patwa, Amit N; Lusic, Hrvoje; Freedman, Jonathan D; Wathier, Michel; Snyder, Brian D; Guermazi, Ali; Grinstaff, Mark W

    2017-07-13

    Contrast agents that go beyond qualitative visualization and enable quantitative assessments of functional tissue performance represent the next generation of clinically useful imaging tools. An optimized and efficient large-scale synthesis of a cationic iodinated contrast agent (CA4+) is described for imaging articular cartilage. Contrast-enhanced CT (CECT) using CA4+ reveals significantly greater agent uptake of CA4+ in articular cartilage compared to that of similar anionic or nonionic agents, and CA4+ uptake follows Donnan equilibrium theory. The CA4+ CECT attenuation obtained from imaging ex vivo human hip cartilage correlates with the glycosaminoglycan content, equilibrium modulus, and coefficient of friction, which are key indicators of cartilage functional performance and osteoarthritis stage. Finally, preliminary toxicity studies in a rat model show no adverse events, and a pharmacokinetics study documents a peak plasma concentration 30 min after dosing, with the agent no longer present in vivo at 96 h via excretion in the urine.

  14. Cell-permeable Ln(III) chelate-functionalized InP quantum dots as multimodal imaging agents.

    Science.gov (United States)

    Stasiuk, Graeme J; Tamang, Sudarsan; Imbert, Daniel; Poillot, Cathy; Giardiello, Marco; Tisseyre, Céline; Barbier, Emmanuel L; Fries, Pascal Henry; de Waard, Michel; Reiss, Peter; Mazzanti, Marinella

    2011-10-25

    Quantum dots (QDs) are ideal scaffolds for the development of multimodal imaging agents, but their application in clinical diagnostics is limited by the toxicity of classical CdSe QDs. A new bimodal MRI/optical nanosized contrast agent with high gadolinium payload has been prepared through direct covalent attachment of up to 80 Gd(III) chelates on fluorescent nontoxic InP/ZnS QDs. It shows a high relaxivity of 900 mM(-1) s(-1) (13 mM(-1 )s(-1) per Gd ion) at 35 MHz (0.81 T) and 298 K, while the bright luminescence of the QDs is preserved. Eu(III) and Tb(III) chelates were also successfully grafted to the InP/ZnS QDs. The absence of energy transfer between the QD and lanthanide emitting centers results in a multicolor system. Using this convenient direct grafting strategy additional targeting ligands can be included on the QD. Here a cell-penetrating peptide has been co-grafted in a one-pot reaction to afford a cell-permeable multimodal multimeric MRI contrast agent that reports cellular localization by fluorescence and provides high relaxivity and increased tissue retention with respect to commercial contrast agents.

  15. Gadolinium Contrast Agent is of Limited Value for Magnetic Resonance Imaging Assessment of Synovial Hypertrophy in Hemophiliacs

    Energy Technology Data Exchange (ETDEWEB)

    Lundin, B.; Berntorp, E.; Pettersson, H.; Wirestam, R.; Jonsson, K.; Staahlberg, F.; Ljung, R. [Dept. of Radiology, Univ Hospital of Lund, Lund (Sweden)

    2007-07-15

    Purpose: To examine the influence of different doses of gadolinium contrast agent on synovial enhancement, to compare magnetic resonance imaging (MRI) findings of synovial hypertrophy and radiographic joint changes in hemophiliacs, and to investigate the value of gadolinium in MRI assessment of synovial hypertrophy in hemophiliacs using dynamic MRI and MRI scoring. Material and Methods: Twenty-one hemophiliacs on prophylactic factor treatment without recent bleeds were subjected to radiography and gadolinium contrast-enhanced dynamic and static MRI of the knee using a standard dose of 0.1 mmol/kg b.w. gadoteridol. In 17 of the patients, the MRI procedure was repeated after a triple dose of gadoteridol. Results: MRI findings of synovial hypertrophy were significantly correlated with Pettersson radiographic scores. In 19 of the 21 MRI investigated joints, administration of contrast agent did not alter the result of the evaluation of synovial hypertrophy. Conclusion: The optimal time interval for volume assessment of synovial hypertrophy after injection of gadolinium contrast agent is dose dependent. Hemophiliacs without recent bleeds have minor to abundant synovial hypertrophy in joints with pronounced radiographic changes. Dynamic MRI is not useful for evaluating hemophilic arthropathy, and gadolinium contrast agent is not routinely indicated for MRI scoring of joints in hemophiliacs.

  16. Gadolinium Contrast Agent is of Limited Value for Magnetic Resonance Imaging Assessment of Synovial Hypertrophy in Hemophiliacs

    International Nuclear Information System (INIS)

    Lundin, B.; Berntorp, E.; Pettersson, H.; Wirestam, R.; Jonsson, K.; Staahlberg, F.; Ljung, R.

    2007-01-01

    Purpose: To examine the influence of different doses of gadolinium contrast agent on synovial enhancement, to compare magnetic resonance imaging (MRI) findings of synovial hypertrophy and radiographic joint changes in hemophiliacs, and to investigate the value of gadolinium in MRI assessment of synovial hypertrophy in hemophiliacs using dynamic MRI and MRI scoring. Material and Methods: Twenty-one hemophiliacs on prophylactic factor treatment without recent bleeds were subjected to radiography and gadolinium contrast-enhanced dynamic and static MRI of the knee using a standard dose of 0.1 mmol/kg b.w. gadoteridol. In 17 of the patients, the MRI procedure was repeated after a triple dose of gadoteridol. Results: MRI findings of synovial hypertrophy were significantly correlated with Pettersson radiographic scores. In 19 of the 21 MRI investigated joints, administration of contrast agent did not alter the result of the evaluation of synovial hypertrophy. Conclusion: The optimal time interval for volume assessment of synovial hypertrophy after injection of gadolinium contrast agent is dose dependent. Hemophiliacs without recent bleeds have minor to abundant synovial hypertrophy in joints with pronounced radiographic changes. Dynamic MRI is not useful for evaluating hemophilic arthropathy, and gadolinium contrast agent is not routinely indicated for MRI scoring of joints in hemophiliacs

  17. [SOS response of DNA repair and genetic cell instability under hypoxic conditions].

    Science.gov (United States)

    Vasil'eva, S V; Strel'tsova, D A

    2011-01-01

    The SOS DNA repair pathway is induced in E. coli as a multifunctional cell response to a wide variety of signals: UV, X or gamma-irradiation, mitomycin C or nalidixic acid treatment, thymine starvation, etc. Triggering of the system can be used as a general and early sign of DNA damage. Additionally, the SOS-response is known to be an "error-prone" DNA repair pathway and one of the sources of genetic instability. Hypoxic conditions are established to be the major factor of genetic instability as well. In this paper we for the first time studied the SOS DNA repair response under hypoxic conditions induced by the well known aerobic SOS-inducers. The SOS DNA repair response was examined as a reaction of E. coli PQ37 [sfiA::lacZ] cells to UVC, NO-donating agents and 4NQO. Here we provide evidence that those agents were able to induce the SOS DNA repair response in E. coli at anaerobic growth conditions. The process does not depend on the transcriptional activity of the universal protein of E. col anaerobic growth Fnr [4Fe-4S]2+ or can not be referred to as an indicator of genetic instability in hypoxic conditions.

  18. Discovery of Radioiodinated Monomeric Anthraquinones as a Novel Class of Necrosis Avid Agents for Early Imaging of Necrotic Myocardium.

    Science.gov (United States)

    Wang, Qin; Yang, Shengwei; Jiang, Cuihua; Li, Jindian; Wang, Cong; Chen, Linwei; Jin, Qiaomei; Song, Shaoli; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2016-02-16

    Assessment of myocardial viability is deemed necessary to aid in clinical decision making whether to recommend revascularization therapy for patients with myocardial infarction (MI). Dianthraquinones such as hypericin (Hyp) selectively accumulate in necrotic myocardium, but were unsuitable for early imaging after administration to assess myocardial viability. Since dianthraquinones can be composed by coupling two molecules of monomeric anthraquinone and the active center can be found by splitting chemical structure, we propose that monomeric anthraquinones may be effective functional groups for necrosis targetability. In this study, eight radioiodinated monomeric anthraquinones were evaluated as novel necrosis avid agents (NAAs) for imaging of necrotic myocardium. All (131)I-anthraquinones showed high affinity to necrotic tissues and (131)I-rhein emerged as the most promising compound. Infarcts were visualized on SPECT/CT images at 6 h after injection of (131)I-rhein, which was earlier than that with (131)I-Hyp. Moreover, (131)I-rhein showed satisfactory heart-to-blood, heart-to-liver and heart-to-lung ratios for obtaining images of good diagnostic quality. (131)I-rhein was a more promising "hot spot imaging" tracer for earlier visualization of necrotic myocardium than (131)I-Hyp, which supported further development of radiopharmaceuticals based on rhein for SPECT/CT ((123)I and (99m)Tc) or PET/CT imaging ((18)F and (124)I) of myocardial necrosis.

  19. Further evidence for the absence of a hypoxic fraction in the 9L rat tumour multicellular spheroid system

    International Nuclear Information System (INIS)

    Gutin, P.H.; Barcellos, M.H.; Shrieve, D.C.; Sano, Y.; Bernstein, M.; Deen, D.F.

    1982-01-01

    The 9L gliosarcoma is an N-methylnitrosourea-induced rat brain tumour that has served as a predictive model for the efficacy of various chemotherapeutic agents against human brain tumours. Because it is one of two known animal tumour models that has no hypoxic fraction, the 9L model is of questionable value for the study of the radiobiology of hypoxic cell sensitizers. Hypoxic 9L monolayer cells are sensitive to misonidazole, as shown by the abrupt decrease in survival after a 2-4 h radiation exposure. However, when 9L spheroids in the size ranges of 200-300, 300-400, 500-600 and 1027+-33μm were incubated in euoxic spinner culture for up to 96 h in 1.5 or 3.0 mM misonidazole, there was no effect on the survival of the dissociated cells over a dose range 0-20 Gy. It is concluded that, in view of the demonstrated sensitivity to misonidazole of hypoxic 9L cells in monolayer culture, this finding provides further evidence that there are no hypoxic cells even in large 9L spheroids with a histologically distinct zone of central necrosis. Moreover, 9L spheroids irradiated in the presence of 3.0 mM misonidazole showed no dose enhancement. (U.K.)

  20. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kuzmanić Šamija, R. [Department of Pediatrics, University Hospital Split, Split (Croatia); Primorac, D. [School of Medicine Split, University of Split, Split (Croatia); Department of Pediatrics, School of Medicine, University of Osijek, Osijek (Croatia); Eberly College of Science, Penn State University, University Park, PA (United States); St. Catherine Speciality Hospital, Zabok (Croatia); Rešić, B. [School of Medicine Split, University of Split, Split (Croatia); Pavlov, V. [Department of Neonatology, University Hospital Split, Split (Croatia); Čapkun, V. [Department of Nuclear Medicine, University Hospital Split, Split (Croatia); Punda, H. [School of Medicine Split, University of Split, Split (Croatia); Lozić, B. [Department of Pediatrics, University Hospital Split, Split (Croatia); Zemunik, T. [Department of Medical Biology, School of Medicine Split, University of Split, Split (Croatia)

    2014-08-15

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  1. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

    International Nuclear Information System (INIS)

    Kuzmanić Šamija, R.; Primorac, D.; Rešić, B.; Pavlov, V.; Čapkun, V.; Punda, H.; Lozić, B.; Zemunik, T.

    2014-01-01

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children

  2. Biofilm imaging in porous media by laboratory X-Ray tomography: Combining a non-destructive contrast agent with propagation-based phase-contrast imaging tools.

    Science.gov (United States)

    Carrel, Maxence; Beltran, Mario A; Morales, Verónica L; Derlon, Nicolas; Morgenroth, Eberhard; Kaufmann, Rolf; Holzner, Markus

    2017-01-01

    X-ray tomography is a powerful tool giving access to the morphology of biofilms, in 3D porous media, at the mesoscale. Due to the high water content of biofilms, the attenuation coefficient of biofilms and water are very close, hindering the distinction between biofilms and water without the use of contrast agents. Until now, the use of contrast agents such as barium sulfate, silver-coated micro-particles or 1-chloronaphtalene added to the liquid phase allowed imaging the biofilm 3D morphology. However, these contrast agents are not passive and potentially interact with the biofilm when injected into the sample. Here, we use a natural inorganic compound, namely iron sulfate, as a contrast agent progressively bounded in dilute or colloidal form into the EPS matrix during biofilm growth. By combining a very long source-to-detector distance on a X-ray laboratory source with a Lorentzian filter implemented prior to tomographic reconstruction, we substantially increase the contrast between the biofilm and the surrounding liquid, which allows revealing the 3D biofilm morphology. A comparison of this new method with the method proposed by Davit et al (Davit et al., 2011), which uses barium sulfate as a contrast agent to mark the liquid phase was performed. Quantitative evaluations between the methods revealed substantial differences for the volumetric fractions obtained from both methods. Namely, contrast agent-biofilm interactions (e.g. biofilm detachment) occurring during barium sulfate injection caused a reduction of the biofilm volumetric fraction of more than 50% and displacement of biofilm patches elsewhere in the column. Two key advantages of the newly proposed method are that passive addition of iron sulfate maintains the integrity of the biofilm prior to imaging, and that the biofilm itself is marked by the contrast agent, rather than the liquid phase as in other available methods. The iron sulfate method presented can be applied to understand biofilm development

  3. Methylene blue microbubbles as a model dual-modality contrast agent for ultrasound and activatable photoacoustic imaging

    Science.gov (United States)

    Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L.; Leung, Ben Y. C.; Goertz, David E.; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F.; Kim, Chulhong

    2014-01-01

    Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

  4. Synthesis and biological evaluation of [{sup 18}F]tetrafluoroborate: a PET imaging agent for thyroid disease and reporter gene imaging of the sodium/iodide symporter

    Energy Technology Data Exchange (ETDEWEB)

    Jauregui-Osoro, Maite; Sunassee, Kavitha; Weeks, Amanda J.; Berry, David J.; Paul, Rowena L.; Cleij, Marcel; O' Doherty, Michael J.; Marsden, Paul K.; Szanda, Istvan; Blower, Philip J. [King' s College London, Division of Imaging Sciences, London (United Kingdom); Banga, Jasvinder Paul [King' s College London, Division of Cell and Gene Based Therapy, London (United Kingdom); Clarke, Susan E.M.; Ballinger, James R. [Guy' s and St Thomas' NHS Trust, Department of Nuclear Medicine, London (United Kingdom); Cheng, Sheue-Yann [National Cancer Institute, Laboratory of Molecular Biology, Bethesda (United States)

    2010-11-15

    The human sodium/iodide symporter (hNIS) is a well-established target in thyroid disease and reporter gene imaging using gamma emitters {sup 123}I-iodide, {sup 131}I-iodide and {sup 99m}Tc-pertechnetate. However, no PET imaging agent is routinely available. The aim of this study was to prepare and evaluate {sup 18}F-labelled tetrafluoroborate ([{sup 18}F]TFB) for PET imaging of hNIS. [{sup 18}F]TFB was prepared by isotopic exchange of BF{sub 4} {sup -} with [{sup 18}F]fluoride in hot hydrochloric acid and purified using an alumina column. Its identity, purity and stability in serum were determined by HPLC, thin-layer chromatography (TLC) and mass spectrometry. Its interaction with NIS was assessed in vitro using FRTL-5 rat thyroid cells, with and without stimulation by thyroid-stimulating hormone (TSH), in the presence and absence of perchlorate. Biodistribution and PET imaging studies were performed using BALB/c mice, with and without perchlorate inhibition. [{sup 18}F]TFB was readily prepared with specific activity of 10 GBq/mg. It showed rapid accumulation in FRTL-5 cells that was stimulated by TSH and inhibited by perchlorate, and rapid specific accumulation in vivo in thyroid (SUV = 72 after 1 h) and stomach that was inhibited 95% by perchlorate. [{sup 18}F]TFB is an easily prepared PET imaging agent for rodent NIS and should be evaluated for hNIS PET imaging in humans. (orig.)

  5. Evaluation of 2-amino-5-nitrothiazole as a hypoxic cell radiosensitizer

    International Nuclear Information System (INIS)

    Rockwell, S.; Mroczkowski, Z.; Rupp, W.D.

    1982-01-01

    The nitroheterocyclic compound 2-amino-5-nitrothiazole (ANT) was evaluated as a hypoxic radiosensitizer. Experiments with bacteria showed that this agent was similar to misonidozole in radiosensitizing activity, but was less cytotoxic and less mutagenic than misonidazole. Experiments with EMT6 tumor cells in culture showed ANT to be an effective hypoxic radiosensitizer, although slightly less active than misonidazole, and to be less cytotoxic than misonidazole. ANT was more toxic to mice than misonidazole and produced a spectrum of symptoms, including hyperactivity and agitation, different from those of misonidazole. The toxicities of ANT and misonidazole were additive. The maximum levels of ANT achieveable in the tumors after ip injection of nontoxic doses of drug were low ( -4 M) and the radiosensitization obtainable with the drug in vivo was inferior to that obtainable with misonidazole. These findings suggest that nitrothiazoles might be an interesting class of nitroheterocyclic radiosensitizers, but that molecules with increased solubility and improved pharmacokinetics would be necessary for efficacy in vivo

  6. Preparation and biodistribution assessment of {sup 111}In-BPAMD as a novel agent for bone SPECT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yousefnia, Hassan; Zolghadri, Samaneh; Jalilian, Amir Reza [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of)

    2015-07-01

    An early diagnosis of bone metastases is very important for providing a profound decision on a subsequent therapy. In this study, a new agent for SPECT-imaging of bone metastases, {sup 111}In-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl) -1,4,7,10-tetraazacyclododec-1-yl) acetic acid ({sup 111}In-BPAMD) complex has been developed with specific activity of 2.85 TBq/mmol. Radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography method indicated high radiochemical purity > 95% at the optimal conditions. The complex demonstrated significant stability at room temperature and in human serum at least for 48 h. Hydroxyapatite (HA) binding assay showed high binding ability of the radiolabeled complex even at the low amounts of HA. Also, log P measurements highlighted the strong hydrophilic nature of the complex. Biodistribution studies as well as planar imaging after injection of the complex into the male Syrian mice showed major accumulation of the labelled compound in the bone tissue. Totally, the obtained results indicated that {sup 111}In-BPAMD has interesting characteristics as an agent for SPECT-imaging of the bone metastases.

  7. Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer early detection using magnetic resonance imaging.

    Science.gov (United States)

    Mouffouk, Fouzi; Simão, Teresa; Dornelles, Daniel F; Lopes, André D; Sau, Pablo; Martins, Jorge; Abu-Salah, Khalid M; Alrokayan, Salman A; Rosa da Costa, Ana M; dos Santos, Nuno R

    2015-01-01

    Early cancer detection is a major factor in the reduction of mortality and cancer management cost. Here we developed a smart and targeted micelle-based contrast agent for magnetic resonance imaging (MRI), able to turn on its imaging capability in the presence of acidic cancer tissues. This smart contrast agent consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock copolymer (poly(ethyleneglycol-b-trimethylsilyl methacrylate)), loaded with a gadolinium hydrophobic complex ((t)BuBipyGd) and exploits the acidic pH in cancer tissues. In vitro MRI experiments showed that (t)BuBipyGd-loaded micelles were pH-sensitive, as they turned on their imaging capability only in an acidic microenvironment. The micelle-targeting ability toward cancer cells was enhanced by conjugation with an antibody against the MUC1 protein. The ability of our antibody-decorated micelles to be switched on in acidic microenvironments and to target cancer cells expressing specific antigens, together with its high Gd(III) content and its small size (35-40 nm) reveals their potential use for early cancer detection by MRI.

  8. Ex Vivo Perfusion-Simulation Measurements of Microbubbles as a Scattering Contrast Agent for Grating-Based X-Ray Dark-Field Imaging.

    Directory of Open Access Journals (Sweden)

    Astrid Velroyen

    Full Text Available The investigation of dedicated contrast agents for x-ray dark-field imaging, which exploits small-angle scattering at microstructures for contrast generation, is of strong interest in analogy to the common clinical use of high-atomic number contrast media in conventional attenuation-based imaging, since dark-field imaging has proven to provide complementary information. Therefore, agents consisting of gas bubbles, as used in ultrasound imaging for example, are of particular interest. In this work, we investigate an experimental contrast agent based on microbubbles consisting of a polyvinyl-alcohol shell with an iron oxide coating, which was originally developed for multimodal imaging and drug delivery. Its performance as a possible contrast medium for small-animal angiography was examined using a mouse carcass to realistically consider attenuating and scattering background signal. Subtraction images of dark field, phase contrast and attenuation were acquired for a concentration series of 100%, 10% and 1.3% to mimic different stages of dilution in the contrast agent in the blood vessel system. The images were compared to the gold-standard iodine-based contrast agent Solutrast, showing a good contrast improvement by microbubbles in dark-field imaging. This study proves the feasibility of microbubble-based dark-field contrast-enhancement in presence of scattering and attenuating mouse body structures like bone and fur. Therefore, it suggests a strong potential of the use of polymer-based microbubbles for small-animal dark-field angiography.

  9. Hypoxic cell turnover in different solid tumor lines

    International Nuclear Information System (INIS)

    Ljungkvist, Anna S.E.; Bussink, Johan; Kaanders, Johannes H.A.M.; Rijken, Paulus F.J.W.; Begg, Adrian C.; Raleigh, James A.; Kogel, Albert J. van der

    2005-01-01

    Purpose: Most solid tumors contain hypoxic cells, and the amount of tumor hypoxia has been shown to have a negative impact on the outcome of radiotherapy. The efficacy of combined modality treatments depends both on the sequence and timing of the treatments. Hypoxic cell turnover in tumors may be important for optimal scheduling of combined modality treatments, especially when hypoxic cell targeting is involved. Methods and Materials: Previously we have shown that a double bioreductive hypoxic marker assay could be used to detect changes of tumor hypoxia in relation to the tumor vasculature after carbogen and hydralazine treatments. This assay was used in the current study to establish the turnover rate of hypoxic cells in three different tumor models. The first hypoxic marker, pimonidazole, was administered at variable times before tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. Hypoxic cell turnover was defined as loss of pimonidazole (first marker) relative to CCI-103F (second marker). Results: The half-life of hypoxic cell turnover was 17 h in the murine C38 colon carcinoma line, 23 h and 49 h in the human xenograft lines MEC82 and SCCNij3, respectively. Within 24 h, loss of pimonidazole-stained areas in C38 and MEC82 occurred concurrent with the appearance of pimonidazole positive cell debris in necrotic regions. In C38 and MEC82, most of the hypoxic cells had disappeared after 48 h, whereas in SCCNij3, viable cells that had been labeled with pimonidazole were still observed after 5 days. Conclusions: The present study demonstrates that the double hypoxia marker assay can be used to study changes in both the proportion of hypoxic tumor cells and their lifespan at the same time. The present study shows that large differences in hypoxic cell turnover rates may exist among tumor lines, with half-lives ranging from 17-49 h

  10. Evaluation of six new /sup 99m/Tc-IDA agents for hepatobiliary imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chervu, L.R.; Joseph, J.A.; Chun, S.B.; Rolleston, R.E.; Synnes, E.I.; Thompson, L.M.; Aldis, A.E.; Rosenthall, L.

    1988-10-01

    IDA derivatives of three substituted benzothiazol, and two substituted chlorophenyl and one substituted pyrazoline compounds have been labeled with /sup 99m/Tc and screened with four rat models with hepatocellular dysfunction manifesting varying degrees of change of liver architecture and hepatocellular damage associated with an active parenchymal destruction, fatty metamorphosis and cirrhosis. Organ distribution studies at 1 h postinjection have been compared in normal and diseased animal models for each agent labeled with /sup 99m/Tc and with /sup 99m/Tc-Disofenin (Disida) and Lidofenin (Hida) and /sup 131/I-Rose Bengal. From the data obtained with the six new IDA derivatives, the distribution kinetics of /sup 99m/Tc-Arclophenin, (N-N'-2-benzoyl-4-chlorophenyl)carbamoylmethyl) imino diacetic acid (Phenida), are closely comparable to /sup 99m/Tc-Disofenin in all animal models. Crossover patient studies (n = 14) for clinical evaluation of /sup 99m/Tc-Arclophenin vs /sup 99m/Tc-Disofenin indicate the close similarity of the 2 agents with regard to blood pool retention, gross liver/heart ratios and liver washout, suggesting Arclophenin as a suitable agent for hepatobiliary function studies. The impaired hepatocellular animal models presented should serve for fast screening of hepatobiliary agents and enable comparison of a series of closely related compounds.

  11. Fostering Multimedia Learning of Science: Exploring the Role of an Animated Agent's Image

    Science.gov (United States)

    Dunsworth, Qi; Atkinson, Robert K.

    2007-01-01

    Research suggests that students learn better when studying a picture coupled with narration rather than on-screen text in a computer-based multimedia learning environment. Moreover, combining narration with the visual presence of an animated pedagogical agent may also encourage students to process information deeper than narration or on-screen…

  12. Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging.

    Science.gov (United States)

    Kaneshiro, Todd L; Ke, Tianyi; Jeong, Eun-Kee; Parker, Dennis L; Lu, Zheng-Rong

    2006-06-01

    The purpose of this study was to synthesize biodegradable Gd-DTPA L-cystine bisamide copolymers (GCAC) as safe and effective, macromolecular contrast agents for magnetic resonance imaging (MRI) and to evaluate their biodegradability and efficacy in MR blood pool imaging in an animal model. Three new biodegradable GCAC with different substituents at the cystine bisamide [R = H (GCAC), CH2CH2CH3 (Gd-DTPA L-cystine bispropyl amide copolymers, GCPC), and CH(CH3)2 (Gd-DTPA cystine bisisopropyl copolymers, GCIC)] were prepared by the condensation copolymerization of diethylenetriamine pentaacetic acid (DTPA) dianhydride with cystine bisamide or bisalkyl amides, followed by complexation with gadolinium triacetate. The degradability of the agents was studied in vitro by incubation in 15 microM cysteine and in vivo with Sprague-Dawley rats. The kinetics of in vivo contrast enhancement was investigated in Sprague-Dawley rats on a Siemens Trio 3 T scanner. The apparent molecular weight of the polydisulfide Gd(III) chelates ranged from 22 to 25 kDa. The longitudinal (T1) relaxivities of GCAC, GCPC, and GCIC were 4.37, 5.28, and 5.56 mM(-1) s(-1) at 3 T, respectively. The polymeric ligands and polymeric Gd(III) chelates readily degraded into smaller molecules in incubation with 15 microM cysteine via disulfide-thiol exchange reactions. The in vitro degradation rates of both the polymeric ligands and macromolecular Gd(III) chelates decreased as the steric effect around the disulfide bonds increased. The agents readily degraded in vivo, and the catabolic degradation products were detected in rat urine samples collected after intravenous injection. The agents showed strong contrast enhancement in the blood pool, major organs, and tissues at a dose of 0.1 mmol Gd/kg. The difference of their in vitro degradability did not significantly alter the kinetics of in vivo contrast enhancement of the agents. These novel GCAC are promising contrast agents for cardiovascular and tumor MRI

  13. Contrast enhanced cartilage imaging: Comparison of ionic and non-ionic contrast agents

    International Nuclear Information System (INIS)

    Wiener, Edzard; Woertler, Klaus; Weirich, Gregor; Rummeny, Ernst J.; Settles, Marcus

    2007-01-01

    Our objective was to compare relaxation effects, dynamics and spatial distributions of ionic and non-ionic contrast agents in articular cartilage at concentrations typically used for direct MR arthrography at 1.5 T. Dynamic MR-studies over 11 h were performed in 15 bovine patella specimens. For each of the contrast agents gadopentetate dimeglumine, gadobenate dimeglumine, gadoteridol and mangafodipir trinatrium three patellae were placed in 2.5 mmol/L contrast solution. Simultaneous measurements of T 1 and T 2 were performed every 30 min using a high-spatial-resolution 'MIX'-sequence. T 1 , T 2 and ΔR 1 , ΔR 2 profile plots across cartilage thickness were calculated to demonstrate the spatial and temporal distributions. The charge is one of the main factors which controls the amount of the contrast media diffusing into intact cartilage, but independent of the charge, the spatial distribution across cartilage thickness remains highly inhomogeneous even after 11 h of diffusion. The absolute ΔR 2 -effect in cartilage is at least as large as the ΔR 1 -effect for all contrast agents. Maximum changes were 5-12 s -1 for ΔR 1 and 8-15 s -1 for ΔR 2 . This study indicates that for morphologically intact cartilage only the amount of contrast agents within cartilage is determined by the charge but not the spatial distribution across cartilage thickness. In addition, ΔR 2 can be considered for quantification of contrast agent concentrations, since it is of the same magnitude and less time consuming to measure than ΔR 1

  14. Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao [Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp [Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan)

    2016-08-05

    The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4–5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba{sup 2+}-sensitive inward rectifier K{sup +} current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca{sup 2+} imaging study revealed that the hypoxic stress enhanced store-operated Ca{sup 2+} (SOC) entry, which was significantly reduced in the presence of 100 μM Ba{sup 2+}. On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba{sup 2+}. We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca{sup 2+} entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. -- Highlights: •Hypoxic culture of brain endothelial cells (BEC) caused membrane hyperpolarization. •This hyperpolarization was due to the increased expression of Kir2.1 channels. •Hypoxia enhanced store-operated Ca{sup 2+} (SOC) entry via Kir2.1 up-regulation. •Expression levels of putative SOC

  15. Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells

    International Nuclear Information System (INIS)

    Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao; Asai, Kiyofumi; Imaizumi, Yuji

    2016-01-01

    The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4–5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba 2+ -sensitive inward rectifier K + current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca 2+ imaging study revealed that the hypoxic stress enhanced store-operated Ca 2+ (SOC) entry, which was significantly reduced in the presence of 100 μM Ba 2+ . On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba 2+ . We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca 2+ entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. -- Highlights: •Hypoxic culture of brain endothelial cells (BEC) caused membrane hyperpolarization. •This hyperpolarization was due to the increased expression of Kir2.1 channels. •Hypoxia enhanced store-operated Ca 2+ (SOC) entry via Kir2.1 up-regulation. •Expression levels of putative SOC channels were not affected by hypoxia.

  16. Method for nuclear magnetic resonance imaging using deuterum as a contrast agent

    Science.gov (United States)

    Kehayias, Joseph J.; Joel, Darrel D.; Adams, William H.; Stein, Harry L.

    1990-01-01

    A method for in vivo NMR imaging of the blood vessels and organs of a patient characterized by using a dark dye-like imaging substance consisting essentially of a stable, high-purity concentration of D.sub.2 O in a solution with water.

  17. Hypothermia for neonatal hypoxic-ischemic encephalopathy: NICHD Neonatal Research Network contribution to the field.

    Science.gov (United States)

    Shankaran, Seetha; Natarajan, Girija; Chalak, Lina; Pappas, Athina; McDonald, Scott A; Laptook, Abbot R

    2016-10-01

    In this article, we summarize the NICHD Neonatal Research Network (NRN) trial of whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy in relation to other randomized controlled trials (RCTs) of hypothermia neuroprotection. We describe the NRN secondary studies that have been published in the past 10 years evaluating clinical, genetic, biochemical, and imaging biomarkers of outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Synthesis, biological evaluation, and baboon PET imaging of the potential adrenal imaging agent cholesteryl-p-[{sup 18}f]fluorobenzoate

    Energy Technology Data Exchange (ETDEWEB)

    Jonson, Stephanie D.; Welch, Michael J. E-mail: welch@mirlink.wustl.edu

    1999-01-01

    Cholesteryl-p-[{sup 18}F]fluorobenzoate ([{sup 18}F]CFB) was investigated as a potential adrenal positron emission tomography (PET) imaging agent for the diagnostic imaging of adrenal disorders. We describe the synthesis, biodistribution, adrenal autoradiography, and baboon PET imaging of [{sup 18}F]CFB. The synthesis of [{sup 18}F]CFB was facilitated by the use of a specially designed microwave cavity that was instrumental in effecting 70-83% incorporation of fluorine-18 in 60 s via [{sup 18}F]fluoro-for-nitro exchange. Tissue distribution studies in mature female Sprague-Dawley rats showed good accumulation of [{sup 18}F]CFB in the steroid-secreting tissues, adrenals and ovaries, at 1 h postinjection. The effectiveness of [{sup 18}F]CFB to accumulate in diseased adrenals was shown through biodistribution studies in hypolipidemic rats, which showed a greater than threefold increase in adrenal uptake at 1 h and increased adrenal/liver and adrenal/kidney ratios. Analysis of the metabolites at 1 h in the blood, adrenals, spleen, and ovaries of hypolipidemic and control rats showed the intact tracer representing greater than 86%, 93%, 92%, and 82% of the accumulated activity, respectively. [{sup 18}F]CFB was confirmed to selectively accumulate in the adrenal cortex versus the adrenal medulla by autoradiography. Normal baboon PET imaging with [{sup 18}F]CFB effectively showed adrenal localization as early as 15 min after injection of the tracer, with enhanced adrenal contrast seen at 60-70 min. These results suggest that [{sup 18}F]CFB may be useful as an adrenal PET imaging agent for assessing adrenal disorders.

  19. [Autonomic regulation at emotional stress under hypoxic conditions in the elderly with physiological and accelerated aging: effect of hypoxic training].

    Science.gov (United States)

    Os'mak, E D; Asanov, É O

    2014-01-01

    The effect of hypoxic training on autonomic regulation in psycho-emotional stress conditions in hypoxic conditions in older people with physiological (25 people) and accelerated (28 people) aging respiratory system. It is shown that hypoxic training leads to an increase in vagal activity indicators (HF) and reduced simpatovagal index (LF/HF), have a normalizing effect on the autonomic balance during stress loads in older people with different types of aging respiratory system.

  20. Development of more efficacious Tc-99m organ imaging agents for use in nuclear medicine by analytical characterization of radiopharmaceutical mixtures

    International Nuclear Information System (INIS)

    Heineman, W.R.

    1992-01-01

    The long-range objective of this research program is the development of more efficacious technetium-99m radiopharmaceuticals for use as imaging agents in diagnostic nuclear medicine. We seek to isolate and develop distinct site imaging agents, each of which has properties optimized to provide diagnostic information concerning a given pathological condition. The specific objectives during the period (9/1/89 to 8/31/92) include: (1) Development of strategies for improving yields of specific Tc-diphosphonate complexes with optimum imaging properties; (2) Development of electrodes for rapid in situ electrochemical generation of skeletal imaging agents; (3) Development of electrochemical sensors for T c and Re imaging agents; (4) Characterization of stable T c - and Re-diphosphonate complexes obtainable in high yield by structural studies with techniques such as NMR, EXAFS, and Raman spectroscopy; (5) Development of improved separation techniques for the characterization of diphosphonate skeletal imaging agents; (6) Evaluation of the effect of the biological milieu on T c -diphosphonate complexes; and (7) Electrochemical studies of technetium and rhenium complexes synthesized by Professor Deutsch's research group for heart and brain imaging

  1. Technical Report (Final): Development of Solid State Reagents for Preparing Radiolabeled Imaging Agents

    Energy Technology Data Exchange (ETDEWEB)

    Kabalka, George W

    2011-05-20

    The goal of this research was on the development of new, rapid, and efficient synthetic methods for incorporating short-lived radionuclides into agents of use in measuring dynamic processes. The initial project period (Year 1) was focused on the preparation of stable, solid state precursors that could be used to efficiently incorporate short-lived radioisotopes into small molecules of use in biological applications (environmental, plant, and animal). The investigation included development and evaluation of new methods for preparing carbon-carbon and carbon-halogen bonds for use in constructing the substrates to be radiolabeled. The second phase (Year 2) was focused on developing isotope incorporation techniques using the stable, boronated polymeric precursors. The final phase (Year 3), was focused on the preparation of specific radiolabeled agents and evaluation of their biodistribution using micro-PET and micro-SPECT. In addition, we began the development of a new series of polymeric borane reagents based on polyethylene glycol backbones.

  2. 64Cu radiolabeled nano-materials as bimodal contrast agent for optical imaging and Positron Emission Tomography (PET)

    International Nuclear Information System (INIS)

    Nonat, A.M.; Roux, A.; Yahia-Ammar, A.; Charbonniere, L.J.; Platas-Iglesias, C.; Camerle, F.

    2015-01-01

    Fluorescent nano-crystals made of semiconductor material, also called Quantum Dots, are ideal agents for long-term or real-time optical imaging. They have been found to outperform traditional organic fluorescent dyes in many ways (size-tunable optical properties, high quantum yields, high extinction coefficients, resistance to photo bleaching). We have developed a microwave method for the synthesis of highly luminescent water soluble CdTe x S 1-x nano-crystals (Φ= 53% at 600 nm). Their surface functionalization has been developed and controlled using a Nile-Red derivative as a fluorescent marker. The same coupling strategy will be used to incorporate 64 Cu-radiotracers for PET imaging at the surface of the Quantum Dots. A large variety of poly-aza-macrocyclic ligands, have been studied in order to optimize the in vivo stability of the 64 Cu-radiolabeled complexes and their efficiency as radiopharmaceuticals

  3. I-123-labelled heptadecanoic acid as myocardial imaging agent: comparison with thallium-201 and first-pass nuclear ventriculography

    International Nuclear Information System (INIS)

    Abdullah, A.Z.; Hawkins, L.A.; Britton, K.E.; Elliott, A.T.; Stephens, J.D.

    1981-01-01

    Results of the use of 123 I-iodoheptadecanoic acid (HA) as a myocardial imaging agent in eight patients and six normals are presented. It was shown that 123 I-HA gave comparable results to the widely used radiopharmaceutical 201 Tl. However the advantages of using 123 I-HA are that the 159 KeV energy is better suited to the conventional gamma camera, it gives a lower radiation dose to the patient and has a lower cost per study. 123 I-HA also has an important advantage in its potential for studying regional myocardial metabolic activity; in one patient, a defect due to ischaemia was seen at rest with 123 I-HA but required stress to make it evident with 201 Tl imaging. (U.K.)

  4. Screening and Monitoring Response to Treatment Using Subsecond Molecular Imaging and Hyperpolarized Contrast Agents

    Science.gov (United States)

    2013-05-01

    DCE-MRI analysis typically involves the application of various pharmacokinetic equations to model the movement of contrast agent molecules between...position over a short time interval due to random, thermally-induced motion (ie, Brownian motion). DW-MRI exploits applied gradients of the main...intracel- lular organelles tend to restrict or hinder the free movement of water.47,48 Moreover, cancerous tissues often show sig- nificantly reduced ADC

  5. Aptamer-crosslinked microbubbles: smart contrast agents for thrombin-activated ultrasound imaging.

    Science.gov (United States)

    Nakatsuka, Matthew A; Mattrey, Robert F; Esener, Sadik C; Cha, Jennifer N; Goodwin, Andrew P

    2012-11-27

    Thrombosis, or malignant blood clotting, is associated with numerous cardiovascular diseases and cancers. A microbubble contrast agent is presented that produces ultrasound harmonic signal only when exposed to elevated thrombin levels. Initially silent microbubbles are activated in the presence of both thrombin-spiked and freshly clotting blood in three minutes with detection limits of 20 nM thrombin and 2 aM microbubbles. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Iodine-123-labeled pH shift brain-imaging agents

    International Nuclear Information System (INIS)

    Blau, M.; Kung, H.F.

    1985-01-01

    HIPDM is an 123 I-labeled agent with a distribution in brain reflecting regional perfusion. This compound is neutral and lipid soluble at blood pH and freely crosses the blood-brain barrier. At the lower pH in brain, it picks up a hydrogen ion and becomes positively charged. In this form the molecule is not lipid soluble and it is trapped in brain

  7. Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

    OpenAIRE

    Nagendra Sanyasihally Ningaraj; Divya eKhaitan

    2013-01-01

    Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB) not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB). Studies in our laboratory have identifi...

  8. Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

    Directory of Open Access Journals (Sweden)

    Ding F

    2014-09-01

    Full Text Available Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM to human renal proximal tubular cells (HK-2 by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the

  9. Peracetic acid as a superior oxidant for preparation of [123I]IBZM: a potential dopamine D-2 receptor imaging agent

    International Nuclear Information System (INIS)

    Kung, Meiping; Kung, H.F.

    1989-01-01

    Various oxidizing agents: chloramine-T, hydrogen peroxide, sodium persulfate, m-chloroperoxybenzoic acid and peracetic acid were examined as the oxidant for preparing radioiodinated IBZM ((S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzami de), which is a useful dopamine D-2 receptor imaging agent. Of all the oxidizing agents tested, peracetic acid appears to be the best agent for no-carrier added radioiodination. The advantages of using peracetic acid as the oxidant for the preparation of [ 125 I] or [ 123 I] IBZM include: high radiochemical yield, high radiochemical purity, and short reaction time at room temperature. (Author)

  10. In vitro effects of piracetam on the radiosensitivity of hypoxic cells (adaptation of MTT assay to hypoxic conditions)

    International Nuclear Information System (INIS)

    Gheuens, E.E.O.; Bruijn, E.A. de; Van der Heyden, S.; Van Oosterom, A.T.; Lagarde, P.; Pooter, C.M.J. de; Chomy, F.

    1995-01-01

    This paper describes the adaptation of the MTT assay to hypoxic conditions in order to test the in vitro effect of piracetam on hypoxic cells and particularly on the radiosensitivity of hypoxic cells since this drug has shown clinical effect on acute and chronic hypoxia. The V79 cell line was selected by reference to preliminary hypoxic experiments using clonogenic assay and euoxic experiments using clonogenic and MTT assays. Cell growth and survival in our hypoxic conditions were assessed using MTT assay with an enclosure and special 48-well plates both made of glass. Growth curves on glass plates after 1-hour exposure to nitrogen versus air were comparable, so there is no bias effect due to gas composition. Survival curves using MTT versus reference clonogenic assay were comparable after radiation exposure in eu- and hypoxic conditions, and confirm the validity of our original technique for creating hypoxia. The Oxygen Enhancement Ratio was of about 3 for 1-hour hypoxic exposure. Piracetam gave no cytotoxic effect up to 10 mM of piracetam. Growth curves after continuous drug exposure and 1-hour euoxic versus hypoxic exposure gave no cytotoxic effect up to 10 mM of piracetam. Survival curves after continuous drug exposure to 10 mM of piracetam gave no significant effect on the radiosensitivity of hypoxic V79 cells using MTT or clonogenic assay. (author). 32 refs., 6 figs

  11. Molecular imaging of a cell-penetrating peptide labeled fluorescein-5-isothiocyanate and MR contrast agents: gadopentetate dimeglumine

    International Nuclear Information System (INIS)

    Liu Min; Guo Youmin; Duan Xiaoyi; Guo Xiaojuan; Yang Junle; Xu Min

    2006-01-01

    Objective: To study the value of a new intracellular contrast agent--cell penetrating peptide labeled Fluorescein-5-isothiocyanate (FITC) and MRI contrast agent, Gadopentetate dimeglumine in molecular imaging. Methods: A new cell penetration peptides (CPPs)sequence LAGRRRRRRRRRK were synthesized in solid phase on the base of arginine (9) and were labelled with FITC (CPP 13 -FITC) and Gd - DTPA (CPP 13 -DTPA-Gd). Hepatic carcinoma cell line-HEPG 2 and mouse bone marrow stem cell was respectively stained by CPP 13 -FITC for different time intervals for observing the uptake and intracellular distribution. HEPG 2 in three l00 mm 2 culture plates was respectively incubated with CPP 13 -DTPA-Gd, Gd- DTPA and Dulbecco minimum essential medium for 30 min and imaged by 1.5 T MRI for studying the intracellular uptake and T 1 WI signal characteristics. Results: The peptide was synthesized by the manual solid-phase method successfully. The calculated molecular weight was 1792.78 and the chemical purity was over 95%. By inverted fluorescence microscope, HEPG 2 and mouse stem cell could transport CPP-FITC in cytoplasm and nuclear in 10 min. By MR imaging, CPP-DTPA-Gd could be uptake by HEPG 2 in 30 min and had a short T 1 short T 2 signal, furthermore. T 1 WI signal intensity ratio between in-tube (Ii) and out-tube (Io) in three groups of three scan slices were shown below: Iil/Io of group 1 (Group 1 was the cell incubated by CPP 13 -DTPA-Gd ) respectively was 2.84, 2.60, 2. 48; Iil/Io of group 2 (Group 2 was the cell incubated by DTPA-Gd) respectively is 1.15, 1.11, 1.12; Iil/Io of group 3 (Group 3 was the controled cell ) respectively was 1.15, 1.11, 1.11. By ANVOA analysis, the signal intensity among group 1, group 2 and group 3 had significant difference(F (1,2) = 201.88 P (1,3) =206.37 P (2,3) =0.529 P=0.507). Conclusion: The new constructed cell penetration peptide on the base of the polyargnine can translocate cell by carting FITC and MRI contrast agent-DTPA-Gd and the

  12. High spatial resolution and high contrast visualization of brain arteries and veins. Impact of blood pool contrast agent and water-selective excitation imaging at 3T

    International Nuclear Information System (INIS)

    Spuentrup, E.; Jacobs, J.E.; Kleimann, J.F.

    2010-01-01

    Purpose: To investigate a blood pool contrast agent and water-selective excitation imaging at 3 T for high spatial and high contrast imaging of brain vessels including the veins. Methods and Results: 48 clinical patients (47 ± 18 years old) were included. Based on clinical findings, twenty-four patients received a single dose of standard extracellular Gadoterate-meglumine (Dotarem registered ) and 24 received the blood pool contrast agent Gadofosveset (Vasovist registered ). After finishing routine MR protocols, all patients were investigated with two high spatial resolution (0.15 mm 3 voxel size) gradient echo sequences in random order in the equilibrium phase (steady-state) as approved by the review board: A standard RF-spoiled gradient-echo sequence (HR-SS, TR/TE 5.1 / 2.3 msec, FA 30 ) and a fat-suppressed gradient-echo sequence with water-selective excitation (HR-FS, 1331 binominal-pulse, TR/TE 8.8 / 3.8 msec, FA 30 ). The images were subjectively assessed (image quality with vessel contrast, artifacts, depiction of lesions) by two investigators and contrast-to-noise ratios (CNR) were compared using the Student's t-test. The image quality and CNR in the HR-FS were significantly superior compared to the HR-SS for both contrast agents (p < 0.05). The CNR was also improved when using the blood pool agent but only to a minor extent while the subjective image quality was similar for both contrast agents. Conclusion: The utilized sequence with water-selective excitation improved image quality and CNR properties in high spatial resolution imaging of brain arteries and veins. The used blood pool contrast agent improved the CNR only to a minor extent over the extracellular contrast agent. (orig.)

  13. Prostate-specific membrane antigen targeted protein contrast agents for molecular imaging of prostate cancer by MRI

    Science.gov (United States)

    Pu, Fan; Salarian, Mani; Xue, Shenghui; Qiao, Jingjuan; Feng, Jie; Tan, Shanshan; Patel, Anvi; Li, Xin; Mamouni, Kenza; Hekmatyar, Khan; Zou, Juan; Wu, Daqing; Yang, Jenny J.

    2016-06-01

    Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high resolution has yet to be achieved due to the lack of contrast agents with significantly improved relaxivity for sensitivity, targeting capabilities and metal selectivity. We have previously reported our creation of a novel class of protein Gd3+ contrast agents, ProCA32, which displayed significantly improved relaxivity while exhibiting strong Gd3+ binding selectivity over physiological metal ions. In this study, we report our effort in further developing biomarker-targeted protein MRI contrast agents for molecular imaging of PSMA. Among three PSMA targeted contrast agents engineered with addition of different molecular recognition sequences, ProCA32.PSMA exhibits a binding affinity of 1.1 +/- 0.1 μM for PSMA while the metal binding affinity is maintained at 0.9 +/- 0.1 × 10-22 M. In addition, ProCA32.PSMA exhibits r1 of 27.6 mM-1 s-1 and r2 of 37.9 mM-1 s-1 per Gd (55.2 and 75.8 mM-1 s-1 per molecule r1 and r2, respectively) at 1.4 T. At 7 T, ProCA32.PSMA also has r2 of 94.0 mM-1 s-1 per Gd (188.0 mM-1 s-1 per molecule) and r1 of 18.6 mM-1 s-1 per Gd (37.2 mM-1 s-1 per molecule). This contrast capability enables the first MRI enhancement dependent on PSMA expression levels in tumor bearing mice using both T1 and T2-weighted MRI at 7 T. Further development of these PSMA-targeted contrast agents are expected to be used for the precision imaging of prostate cancer at an early stage and to monitor disease progression and staging, as well as determine the effect of therapeutic treatment by non-invasive evaluation of the PSMA level using MRI.Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high

  14. Preparation and Evaluation of Multiple Nanoemulsions Containing Gadolinium (III) Chelate as a Potential Magnetic Resonance Imaging (MRI) Contrast Agent.

    Science.gov (United States)

    Sigward, Estelle; Corvis, Yohann; Doan, Bich-Thuy; Kindsiko, Kadri; Seguin, Johanne; Scherman, Daniel; Brossard, Denis; Mignet, Nathalie; Espeau, Philippe; Crauste-Manciet, Sylvie

    2015-09-01

    The objective was to develop, characterize and assess the potentiality of W1/O/W2 self-emulsifying multiple nanoemulsions to enhance signal/noise ratio for Magnetic Resonance Imaging (MRI). For this purpose, a new formulation, was designed for encapsulation efficiency and stability. Various methods were used to characterize encapsulation efficiency ,in particular calorimetric methods (Differential Scanning Calorimetry (DSC), thermogravimetry analysis) and ultrafiltration. MRI in vitro relaxivities were assessed on loaded DTPA-Gd multiple nanoemulsions. Characterization of the formulation, in particular of encapsulation efficiency was a challenge due to interactions found with ultrafiltration method. Thanks to the specifically developed DSC protocol, we were able to confirm the formation of multiple nanoemulsions, differentiate loaded from unloaded nanoemulsions and measure the encapsulation efficiency which was found to be quite high with a 68% of drug loaded. Relaxivity studies showed that the self-emulsifying W/O/W nanoemulsions were positive contrast agents, exhibiting higher relaxivities than those of the DTPA-Gd solution taken as a reference. New self-emulsifying multiple nanoemulsions that were able to load satisfactory amounts of contrasting agent were successfully developed as potential MRI contrasting agents. A specific DSC protocol was needed to be developed to characterize these complex systems as it would be useful to develop these self-formation formulations.

  15. A phase 2 clinical study of 99mTc-MAG3 injectable, a dynamic renal imaging agent

    International Nuclear Information System (INIS)

    Torizuka, Kanji; Yamamoto, Kazutaka; Nishibuchi, Shigeo; Ishibashi, Akira; Ikekubo, Katsuji.

    1993-01-01

    A phase 2 clinical study of 99m Tc-mercapto acetyl glycylglycylglycine ( 99m Tc-MAG3) injectable, a new dynamic renal imaging agent, was performed in 110 patients with renal and/or urinary disorders to evaluate the safety, efficacy and optimal dose of this agent. Neither adverse reactions nor abnormal laboratory findings due to intravenous administration of 99m Tc-MAG3 were observed. The investigators evaluated the clinical efficacy of 99m Tc-MAG3 was to be effective in 96 of 97 cases. Among the doses of 92.5 MBq, 370 MBq and 555 MBq, the dose of 92.5 MBq was not large enough to provide adequate-quality blood flow images or reliable information for evaluation of the renal blood flow. It was concluded that the optimal dose range of 99m Tc-MAG3 was 185-555 MBq with 370 MBq as the standard dose. Also, we summarize that 555 MBq is especially recommendable when detailed blood flow information is required. These results indicate that 99m Tc-MAG3 injectable is useful for the diagnosis of renal and urinary disorders. (author)

  16. Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments.

    Science.gov (United States)

    Nwe, Kido; Huang, Ching-Hui; Tsourkas, Andrew

    2013-10-24

    Neoplastic lesions can create a hostile tumor microenvironment with low extracellular pH. It is commonly believed that these conditions can contribute to tumor progression as well as resistance to therapy. We report the development and characterization of a pH-responsive magnetic resonance imaging contrast agent for imaging the acidic tumor microenvironment. The preparation included the conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5-dioxo-1-pyrrolidinyl) ester (DOTA-NHS) to the surface of a water-soluble glycol chitosan (GC) polymer, which contains pH-titrable primary amines, followed by gadolinium complexation (GC-NH2-GdDOTA). GC-NH2-GdDOTA had a chelate-to-polymer ratio of approximately1:24 and a molar relaxivity of 9.1 mM(-1) s(-1). GC-NH2-GdDOTA demonstrated pH-dependent cellular association in vitro compared to the control. It also generated a 2.4-fold enhancement in signal in tumor-bearing mice 2 h postinjection. These findings suggest that glycol chitosan coupled with contrast agents can provide important diagnostic information about the tumor microenvironment.

  17. Availability of perfluoroctylbromide (PFOB) emulsion used as agent in the liver tumor imaging of computed tomography (CT)

    International Nuclear Information System (INIS)

    Ozawa, Takachika

    1986-01-01

    We carried out a fundamental study on the availability of perfluoroctylbromide (PFOB) emulsion used as an agent in the liver tumor imaging of computed tomography (CT). For this study, we used emulsified yolk phospolipid as a surfactant for PFOB emulsion because it is generally considered to have higher safety relative to the administration to the humans. In the rabbits' liver tumor model in which VX 2 tumor cell was implanted into their livers, we observed increases in the CT values of the livers when 5 to 10 ml/kg of PFOB emulsion (20 % w/v) was administered into the vein, and also ringlike enhancement and increases in the CT values on the tumor rim when 20 ml/kg of PFOB emulsion was administered. In addition, in the chemical analysis of a gas chromatography, we also observed significant increases in the PFOB concentration on the tumor rim, compared with those of normal liver parenchyma, when 20 ml/kg of PFOB emulsion was given. In the finding of CT values in the human liver tumor by means of organ perfusion system, we recognized increases in the CT values (induced by the accumulation of PFOB emulsion) on the rim of the metastatic tumor of colon cancer. These results suggest that PFOB emulsion has certain availability as an agent for the liver tumor imaging of computed tomography (CT). (author)

  18. Biodegradable human serum albumin nanoparticles as contrast agents for the detection of hepatocellular carcinoma by magnetic resonance imaging.

    Science.gov (United States)

    Watcharin, Waralee; Schmithals, Christian; Pleli, Thomas; Köberle, Verena; Korkusuz, Hüdayi; Huebner, Frank; Zeuzem, Stefan; Korf, Hans W; Vogl, Thomas J; Rittmeyer, Claudia; Terfort, Andreas; Piiper, Albrecht; Gelperina, Svetlana; Kreuter, Jörg

    2014-05-01

    Tumor visualization by magnetic resonance imaging (MRI) and nanoparticle-based contrast agents may improve the imaging of solid tumors such as hepatocellular carcinoma (HCC). In particular, human serum albumin (HSA) nanoparticles appear to be a suitable carrier due to their safety and feasibility of functionalization. In the present study HSA nanoparticles were conjugated with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) using carbodiimide chemistry. The nanoparticles had a uniform spherical shape and a diameter of 235±19nm. For better optical visualization in vitro and in vivo, the HSA-Gd nanoparticles were additionally labeled with rhodamine 123. As shown by confocal microscopy and flow cytometry analysis, the fluorescent nanoparticles were readily taken up by Huh-7 hepatocellular carcinoma cells. After 24h incubation in blood serum, less than 5% of the Gd(III) was released from the particles, which suggests that this nanoparticulate system may be stable in vivo and, therefore, may serve as potentially safe T1 MRI contrast agent for MRI of hepatocellular carcinoma. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Subcellular SIMS imaging of gadolinium isotopes in human glioblastoma cells treated with a gadolinium containing MRI agent

    Science.gov (United States)

    Smith, Duane R.; Lorey, Daniel R.; Chandra, Subhash

    2004-06-01

    Neutron capture therapy is an experimental binary radiotherapeutic modality for the treatment of brain tumors such as glioblastoma multiforme. Recently, neutron capture therapy with gadolinium-157 has gained attention, and techniques for studying the subcellular distribution of gadolinium-157 are needed. In this preliminary study, we have been a