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High Uptake (high + uptake)
Selected AbstractsRadioevaluation of PAMs, CMs, and PS-Lip as an oral carrier for vaccine delivery into intestinal Peyer's patchesDRUG DEVELOPMENT RESEARCH, Issue 12 2006Chang-Moon Lee Abstract The aim of the present study was to evaluate the utility of pullulan acetate microparticles (PAMs), chitosan micropaticles (CMs), and dipalmitoylphosphatidyl-serine-liposomes (PS-Lip) as oral carriers for delivery to the intestinal Peyer's patches (PPs). To monitor PP delivery after oral administration, PAMs, CMs, and PS-Lip were radiolabeled with 99mTc. Radiolabeling efficiencies of the particles were 95±2.5% (PAMs), 87±4.3% (CMs), and 77.2±5.8% (PS-Lip). In delivery studies to the PPs, the percentage of PS-Lip taken up to the PPs was 3.8 × 10,3±0.3% of the administered dose with PS-Lip group showed significantly high uptake compared to the PAM and CM groups. These results suggest that PS-Lip may be used as a potential system for developing an oral delivery carrier. Drug Dev. Res. 67:884,889, 2006. © 2007 Wiley-Liss, Inc. [source] Radiosynthesis and in vivo study of [18F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine: a promising new sigma-1 receptor ligandJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2005Jun Zhao Abstract The novel sigma-1 receptor PET radiotracer [18F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([18F]WLS1.002, [18F]-2) was synthesized (n=6) by heating the corresponding N -ethylmesylate precursor in an anhydrous acetonitrile solution containing [18F]fluoride, Kryptofix K222 and potassium carbonate for 15 min. Purification was accomplished by reverse-phase HPLC methods, providing [18F]-2 in 59±8% radiochemical yield (EOB), with specific activity of 2.89±0.80 Ci/µmol (EOS) and radiochemical purity of 98.3±2.1%. Rat biodistribution studies revealed relatively high uptake in many organs known to contain sigma-1 receptors, including the lungs, kidney, heart, spleen, and brain. Good clearance from normal tissues was observed over time. Blocking studies (60 min) demonstrated high (>80%) specific binding of [18F]-2 in the brain, with reduction also noted in other organs known to express these sites. Copyright © 2005 John Wiley & Sons, Ltd. [source] Binding characteristics and sensitivity to endogenous dopamine of [11C]-(+)-PHNO, a new agonist radiotracer for imaging the high-affinity state of D2 receptors in vivo using positron emission tomographyJOURNAL OF NEUROCHEMISTRY, Issue 4 2006Nathalie Ginovart Abstract [11C]-(+)-PHNO (4-propyl-9-hydroxynaphthoxazine) is a new agonist radioligand that provides a unique opportunity to measure the high-affinity states of the D2 receptors (D2 -high) using positron emission tomography (PET). Here we report on the distribution, displaceablity, specificity and modeling of [11C]-(+)-PHNO and compare it with the well characterized antagonist D2 radioligand, [11C]raclopride, in cat. [11C]-(+)-PHNO displayed high uptake in striatum with a mean striatal binding potential (BP) of 3.95 ± 0.85. Pre-treatment with specific D1 (SCH23390), D2 (raclopride, haloperidol) and D3 receptor (SB-277011) antagonists indicated that [11C]-(+)-PHNO binding in striatum is specific to D2 receptors. Within-subject comparisons showed that [11C]-(+)-PHNO BP in striatum was almost 2.5-fold higher than that measured with [11C]-(,)-NPA ([11C]-(,)-N-propyl-norapomorphine). Comparison of the dose-effect of amphetamine (0.1, 0.5 and 2 mg/kg; i.v.) showed that [11C]-(+)-PHNO was more sensitive to the dopamine releasing effect of amphetamine than [11C]raclopride. Amphetamine induced up to 83 ± 4% inhibition of [11C]-(+)-PHNO BP and only up to 56 ± 8% inhibition of [11C]raclopride BP. Scatchard analyses of [11C]-(+)-PHNO and [11C]raclopride bindings in two cats showed that the Bmax obtained with the agonist (29.6 and 32.9 pmol/mL) equalled that obtained with the antagonist (30.6 and 33.4 pmol/mL). The high penetration of [11C]-(+)-PHNO in brain, its high signal-to-noise ratio, its favorable in vivo kinetics and its high sensitivity to amphetamine shows that [11C]-(+)-PHNO has highly suitable characteristics for probing the D2 -high with PET. [source] Rosai,Dorfman disease presenting as a solitary mediastinal massPATHOLOGY INTERNATIONAL, Issue 4 2009Akira I. Hida Rosai,Dorfman disease (RDD) involving an extranodal site is a diagnostic challenge. Reported herein is the case of a 67-year-old man who presented with a solitary superior mediastinal mass. The lesion was clinically suspected of malignancy including lymphoma because of its high uptake during a 67Ga-scintigram and 18F-fluorodeoxyglucose,positron emission tomography. There was no evidence of spread of the disease. Histology of thoracoscopic biopsy specimens indicated granulomatous lesion with infiltration of lymphocytes, plasma cells, and histiocytes with lymphocytes engulfed in their cytoplasm. The lesion did not contain lymph node or thymic elements. On immunohistochemistry the histiocytes were positive for S-100 protein, CD68, and CD163 but were negative for CD1a. These findings suggested a diagnosis of RDD. Despite lack of intervention, the lesion remained almost the same size for 3 years. To the best of the authors' knowledge this is the first case of RDD presenting as a solitary mediastinal mass. [source] Heterozygote Carrier Testing in High Schools Abroad: What are the Lessons for the U.S.?THE JOURNAL OF LAW, MEDICINE & ETHICS, Issue 4 2006Lainie Friedman Ross M.D., Ph.D.Article first published online: 23 NOV 200 The main value of carrier detection in the general population is to determine reproductive risks. In this manuscript I examine the practice of providing carrier screening programs in the school setting. While the data show that high school screening programs can achieve high uptake, I argue that this may reflect a lack of full understanding about risks, benefits, and alternatives, and the right not to know. It may also reflect the inherent coercion in group testing, particularly for adolescents who are prone to peer pressure. The problem of carrier screening in the schools is compounded when the condition has a predilection for certain groups based on race, ethnicity or religion. I examine programs around the world that seek to test high school students for Tay Sachs and Cystic Fibrosis carrier status. I argue that carrier programs should be designed so as to minimize stigma and to allow individuals to refuse. The mandatory school environment cannot achieve this. Rather, I conclude that screening programs should be designed to attract young adults and not adolescents to participate in a more voluntary venue. [source] Synthesis of a novel boronated 1-aminocyclobutanecarboxylic acid as a potential boron neutron capture therapy agent,APPLIED ORGANOMETALLIC CHEMISTRY, Issue 6-7 2003George W. Kabalka Abstract A boronated aminocyclobutanecarboxylic acid was synthesized for potential use in neutron capture therapy. The synthesis involves the preparation of hydroxymethylcyclobutanone ketal, which is then converted to an amino acid using Bucherer,Strecker methodology. The molecule is modeled after the unnatural amino acid, 1-aminocyclobutanecarboxylic acid, which has demonstrated high uptake in brain tumors. Copyright © 2003 John Wiley & Sons, Ltd. [source] Challenges, lessons learned and results following the implementation of a human papilloma virus school vaccination program in South AustraliaAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 4 2009Maureen Watson Abstract Objective: To describe the process and challenges in the roll out of a large cervical cancer vaccination program to protect against human papilloma virus (HPV) infection. Methods: This article describes the process of planning and implementing a HPV vaccination program using the existing state-wide framework that supports vaccine delivery to all 219 high schools in South Australia. The decision was made to offer three doses of HPV vaccine to 50,191 female students in Years 8-12 during the 2007 school year. Results: By November 2007, despite many challenges, the school vaccination program had delivered 107,541 doses of HPV vaccine. Coverage of dose 1 was highest in Years 8 (83%) and 10 (70%), but was reduced for doses 2 and 3 in all year levels, with dose 3 coverage ranging from 55% (Year 11) to 77% (Year 8). Conclusions: The introduction of a large school-based vaccination program at short notice posed new challenges for the co-ordination and implementation. Not all schools supported the introduction of HPV vaccine, resulting in reduced access for some students. Negative media messages provided a strong platform for individuals who opposed vaccination. These factors may have contributed to the less-than-expected uptake of HPV vaccine. Implications: Historically, there has been high uptake of other vaccines given to adolescents. However, the introduction of HPV vaccine may have adversely affected the uptake of Hepatitis B vaccine, given concurrently in the school program. Further studies are needed to determine if this is likely to have a negative effect on the public perception of the value of vaccine programs in general. [source] Residual tumor uptake of [99mTc]-sestamibi after neoadjuvant chemotherapy for locally advanced breast carcinoma predicts survivalCANCER, Issue 4 2005Lisa K. Dunnwald B.S. Abstract BACKGROUND Studies utilizing serial [99mTc]-sestamibi (MIBI) scintimammography have reported accurate prediction of tumor response in patients with locally advanced breast carcinoma (LABC) undergoing neoadjuvant chemotherapy. The pathologic response of LABC to presurgical treatment regimens is a prognostic indicator of survival. The authors tested whether MIBI uptake posttherapy predicted survival. METHODS Sixty-two patients with LABC underwent MIBI scintimammography just before chemotherapy and 2 months after treatment initiation. An additional MIBI scan was performed if treatment lasted > 3 months. The affected breast was imaged within 10 minutes after injection to reflect early uptake, which the authors have shown to be related to tumor blood flow. MIBI uptake was quantified using the lesion-to-normal breast (L:N) ratio. Most patients (93%) received weekly dose-intensive doxorubicin-based treatment. Disease-free survival (DFS) and overall survival (OS) were compared with posttherapy primary MIBI uptake and with other established prognostic factors for neoadjuvantly treated LABC, namely, primary tumor pathologic response and posttherapy axillary lymph node status. RESULTS Patients with high uptake on the last observed MIBI scan (i.e., the L:N ratio was greater than the median value) had poorer DFS and OS (P < 0.01 and P = 0.01, respectively). Residual MIBI uptake retained independent prognostic significance in preliminary multivariate analysis that included other established prognostic markers. CONCLUSIONS High primary breast tumor MIBI uptake after neoadjuvant chemotherapy predicted poor survival, suggesting serial MIBI imaging may provide a useful quantitative surrogate end point for neoadjuvant chemotherapy trials. Given the association between MIBI uptake and tumor blood flow, this prognostic capability may be related to retained tumor vascularity after treatment. Cancer 2005. © 2005 American Cancer Society. [source] In vitro and preclinical studies of targeted alpha therapy (TAT) for colorectal cancerCOLORECTAL DISEASE, Issue 5 2001S. M. A. Rizvi Introduction Effective targeted cancer therapy requires high selectivity and cytotoxicity of the labelled product. We report the preparation and testing of anticolorectal cancer monoclonal antibody c30.6 radioimmunoconjugates (RIC) labelled with alpha-emitting Bismuth-213 and positron emitting Terbium-152 using two chelators, viz. Cyclic dianhydride of diethylenetriaminepentacetic acid (DTPA) and CHX-A,, (a DTPA derivative). Methods Selectivity and stability of the RIC were tested in vitro (flow cytometry) and in vivo (biodistribution, organ/tumour uptake and retention). Cytotoxicity assays were carried out using tritiated thymidine uptake (inhibition of DNA synthesis) and MTS assay. Results High labelling efficiency (ranging between 89 and 91%) and stability over 2,5 half-lives of the isotopes were seen. Kidney retention was not seen in contrast to high uptake and retention of both conjugates in tumours. Flow cytometry studies showed high specificity of the antibody before and after labelling and this unchanged targeting behaviour was reflected in cytotoxicity assays. These assays showed that only alpha-labelled antibody could selectively kill the cancer cells for activities as low as 2,3 ,Ci. The study also revealed that free isotopes or isotopes bound to nonspecific antibodies did not kill cancer cells. Conclusion The stability of the RICs and outstanding cytotoxicity of the alpha emitter, together with no kidney retention and high tumour uptake and retention of the radiolabel, offers a new approach for the potential control of colorectal cancer. [source] | |||||||||||||