160 research outputs found
PET Imaging of Carbonic Anhydrase IX Expression of HT-29 Tumor Xenograft Mice with 68Ga-Labeled Benzenesulfonamides
Synthesis and evaluation of 18F-labeled carbonic anhydrase IX inhibitors for imaging with positron emission tomography
Two carbonic anhydrase IX (CA IX) inhibitors were radiolabeled with (18)F, and evaluated for imaging CA IX expression. Despite good affinity for CA IX and excellent plasma stability, uptake of both tracers in CA IX-expressing HT-29 tumor xenografts in mice was low. (18)F-FEC accumulated predominately in the liver and nasal cavity, whereas a significant amount of (18)F-U-104 was retained in blood. Due to minimal uptake in HT-29 tumors compared to other organs/tissues, these two tracers are not suitable for use for CA IX-targeted imaging
Fabrication and Characterization of CuInSe 2
The chalcopyrite CuInSe2 thin film synthesized via a low temperature solid state reaction from CuSe and InSe powders was investigated using X-ray diffractomy (XRD), scanning electron microscope (SEM), energy dispersive spectrometer (EDS), transmission electron microscopy (TEM), and UV-vis absorption spectroscopy. CuSe and InSe phases react and directly transform into CuInSe2 without the occurrence of any intermediate phase. The morphology of the newly formed CuInSe2 crystalline was close to that of the CuSe reactant particle based on the TEM results, which indicate that the solid state reaction kinetics may be dominated by the In3+ ions diffusion. The CuInSe2 thin film prepared from the solid state reaction did not use the selenide process; its band gap might reach 1.06 eV, which is competent and suitable to be used for a thin film solar cell light absorption layer
Subamolide A Induces Mitotic Catastrophe Accompanied by Apoptosis in Human Lung Cancer Cells
This study investigated the anticancer effects of subamolide A (Sub-A), isolated from Cinnamomum subavenium, on human nonsmall cell lung cancer cell lines A549 and NCI-H460. Treatment of cancer cells with Sub-A resulted in decreased cell viability of both lung cancer cell lines. Sub-A induced lung cancer cell death by triggering mitotic catastrophe with apoptosis. It triggered oxidant stress, indicated by increased cellular reactive oxygen species (ROS) production and decreased glutathione level. The elevated ROS triggered the activation of ataxia-telangiectasia mutation (ATM), which further enhanced the ATF3 upregulation and subsequently enhanced p53 function by phosphorylation at Serine 15 and Serine 392. The antioxidant, EUK8, significantly decreased mitotic catastrophe by inhibiting ATM activation, ATF3 expression, and p53 phosphorylation. The reduction of ATM and ATF3 expression by shRNA decreased Sub-A-mediated p53 phosphorylation and mitotic catastrophe. Sub-A also caused a dramatic 70% reduction in tumor size in an animal model. Taken together, cell death of lung cancer cells in response to Sub-A is dependent on ROS generation, which triggers mitotic catastrophe followed by apoptosis. Therefore, Sub-A may be a novel anticancer agent for the treatment of nonsmall cell lung cancer
Recurrent disturbances and the degradation of hard coral communities in Taiwan
Recurrent disturbances can have a critical effect on the structure and function of coral reef communities. In this study, long-term changes were examined in the hard coral community at Wanlitung, in southern Taiwan, between 1985 and 2010. In this 26 year interval, the reef has experienced repeated disturbances that include six typhoons and two coral-bleaching events. The frequency of disturbance has meant that species susceptible to disturbance, such as those in the genus Acropora and Montipora have almost disappeared from the reef. Indeed, almost all hard coral species have declined in abundance, with the result that total hard coral cover in 2010 (17.7%) was less than half what it was in 1985 (47.5%). In addition, macro-algal cover has increased from 11.3% in 2003 to 28.5% in 2010. The frequency of disturbance combined with possible chronic influence of a growing human population mean that a diverse reef assemblage is unlikely to persist on this reef into the future
Synthesis and Evaluation of [F-18]FEtLos and [F-18]AMBF(3)Los as Novel F-18-Labelled Losartan Derivatives for Molecular Imaging of Angiotensin II Type 1 Receptors
Losartan is widely used in clinics to treat cardiovascular related diseases by selectively blocking the angiotensin II type 1 receptors (AT(1)Rs), which regulate the renin-angiotensin system (RAS). Therefore, monitoring the physiological and pathological biodistribution of AT(1)R using positron emission tomography (PET) might be a valuable tool to assess the functionality of RAS. Herein, we describe the synthesis and characterization of two novel losartan derivatives PET tracers, [F-18]fluoroethyl-losartan ([F-18]FEtLos) and [F-18]ammoniomethyltrifluoroborate-losartan ([F-18]AMBF(3)Los). [F-18]FEtLos was radiolabeled by F-18-fluoroalkylation of losartan potassium using the prosthetic group 2-[F-18]fluoroethyl tosylate; whereas [F-18]AMBF(3)Los was prepared following an one-step F-18-F-19 isotopic exchange reaction, in an overall yield of 2.7 +/- 0.9% and 11 +/- 4%, respectively, with high radiochemical purity (>95%). Binding competition assays in AT(1)R-expressing membranes showed that AMBF(3)Los presented an almost equivalent binding affinity (K-i 7.9 nM) as the cold reference Losartan (K-i 1.5 nM), unlike FEtLos (K-i 2000 nM). In vitro and in vivo assays showed that [F-18]AMBF(3)Los displayed a good binding affinity for AT(1)R-overexpressing CHO cells and was able to specifically bind to renal AT(1)R. Hence, our data demonstrate [F-18]AMBF(3)Los as a new tool for PET imaging of AT(1)R with possible applications for the diagnosis of cardiovascular, inflammatory and cancer diseases
Polycythemia vera as a presentation of renal angiomyolipoma: a case report
<p>Abstract</p> <p>Introduction</p> <p>Angiomyolipoma is a common benign renal tumor composed of thick-walled blood vessels, smooth muscle, and adipose tissue. It may be found incidentally during workup for suspected renal disease. Although angiomyolipoma may present as a palpable, tender renal mass with flank pain and gross or microscopic hematuria, many patients are asymptomatic. Erythrocytosis is an unusual presentation, and malignant transformation may be suspected. This report describes a rare case of a woman diagnosed with renal angiomyolipoma and polycythemia vera. The report discusses the differential diagnosis using erythropoietin, erythropoietin-receptor and Janus kinase 2.</p> <p>Case presentation</p> <p>A 79-year-old Chinese woman was diagnosed with erythrocytosis according to World Health Organization criteria. An upper left renal pole angiomyolipoma was successfully ablated after multiple phlebotomy treatments. Red cell count immediately returned to normal, but gradually increased after 4 months. Polycythemia vera was finally diagnosed by positive mutation of Janus kinase 2 and negative erythropoietin protein expression. Her clinical symptoms improved with regular phlebotomy and hydroxyurea treatment.</p> <p>Conclusion</p> <p>Concurrent occurence of angiomyolipoma and polycythemia vera is rare. Polycythemia vera can be easily missed. Polycythemia vera can be confirmed with high specificity and sensitivity by the acquired somatic mutation. Surgical intervention for this renal tumor should be avoided unless malignancy or renal cell carcinoma is suspected or to prevent spontaneous rupture of larger tumors.</p
Molecular Imaging and Radionuclide Therapy of Melanoma Targeting the Melanocortin 1 Receptor
Melanoma is a deadly disease at late metastatic stage, and early diagnosis and accurate staging remain the key aspects for managing melanoma. The melanocortin 1 receptor (MC1 R) is overexpressed in primary and metastatic melanomas, and its endogenous ligand, the α-melanocyte-stimulating hormone (αMSH), has been extensively studied for the development of MC1 R-targeted molecular imaging and therapy of melanoma. Natural αMSH is not well suited for this purpose due to low stability in vivo. Unnatural amino acid substitutions substantially stabilized the peptide, while cyclization via lactam bridge and metal coordination further improved binding affinity and stability. In this study, we summarized the development and the in vitro and in vivo characteristics of the radiolabeled αMSH analogues, including 99m Tc-, 111 In-, 67 Ga-, or 125 I-labeled αMSH analogues for imaging with single-photon emission computed tomography; 68 Ga-, 64 Cu-, or 18 F-labeled αMSH analogues for imaging with positron emission tomography; and 188 Re-, 177 Lu-, 90 Y-, or 212 Pb-labeled αMSH analogues for radionuclide therapy. These radiolabeled αMSH analogues showed promising results with high tumor uptake and rapid normal tissue activity clearance in the preclinical model of B16F1 and B16F10 mouse melanomas. These results highlight the potential of using radiolabeled αMSH analogues in clinical applications for molecular imaging and radionuclide therapy of melanoma
Application of Cleavable Linkers to Improve Therapeutic Index of Radioligand Therapies
Radioligand therapy (RLT) is an emergent drug class for cancer treatment. The dose administered to cancer patients is constrained by the radiation exposure to normal tissues to maintain an appropriate therapeutic index. When a radiopharmaceutical or its radiometabolite is retained in the kidneys, radiation dose deposition in the kidneys can become a dose-limiting factor. A good exemplar is [177Lu]Lu-DOTATATE, where patients receive a co-infusion of basic amino acids for nephroprotection. Besides peptides, there are other classes of targeting vectors like antibody fragments, antibody mimetics, peptidomimetics, and small molecules that clear through the renal pathway. In this review, we will review established and emerging strategies that can be used to mitigate radiation-induced nephrotoxicity, with a focus on the development and incorporation of cleavable linkers for radiopharmaceutical designs. Finally, we offer our perspectives on cleavable linkers for RLT, highlighting future areas of research that will help advance the technology.Medicine, Faculty ofNon UBCMedical Oncology, Division ofMedicine, Department ofRadiology, Department ofReviewedFacult
A Systematic Review of Molecular Imaging Agents Targeting Bradykinin B1 and B2 Receptors
Kinins, bradykinin and kallidin are vasoactive peptides that signal through the bradykinin B1 and B2 receptors (B1R and B2R). B2R is constitutively expressed in healthy tissues and mediates responses such as vasodilation, fluid balance and retention, smooth muscle contraction, and algesia, while B1R is absent in normal tissues and is induced by tissue trauma or inflammation. B2R is activated by kinins, while B1R is activated by kinins that lack the C-terminal arginine residue. Perturbations of the kinin system have been implicated in inflammation, chronic pain, vasculopathy, neuropathy, obesity, diabetes, and cancer. In general, excess activation and signaling of the kinin system lead to a pro-inflammatory state. Depending on the disease context, agonism or antagonism of the bradykinin receptors have been considered as therapeutic options. In this review, we summarize molecular imaging agents targeting these G protein-coupled receptors, including optical and radioactive probes that have been used to interrogate B1R/B2R expression at the cellular and anatomical levels, respectively. Several of these preclinical agents, described herein, have the potential to guide therapeutic interventions for these receptors.Medicine, Faculty ofNon UBCRadiology, Department ofReviewedFacult
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