scholarly journals Pretargeting CD45 enhances the selective delivery of radiation to hematolymphoid tissues in nonhuman primates

Blood ◽  
2009 ◽  
Vol 114 (6) ◽  
pp. 1226-1235 ◽  
Author(s):  
Damian J. Green ◽  
John M. Pagel ◽  
Eneida R. Nemecek ◽  
Yukang Lin ◽  
Aimee Kenoyer ◽  
...  
Keyword(s):  
Macaca Fascicularis ◽  
Nonhuman Primates ◽  
Second Step ◽  
Malignant Cells ◽  
Normal Organ ◽  
Therapeutic Advantage ◽  
Rapid Clearance ◽  
Selective Delivery ◽  
Pretargeted Radioimmunotherapy ◽  
Time Point

Abstract Pretargeted radioimmunotherapy (PRIT) is designed to enhance the directed delivery of radionuclides to malignant cells. Through a series of studies in 19 nonhuman primates (Macaca fascicularis), the potential therapeutic advantage of anti-CD45 PRIT was evaluated. Anti-CD45 PRIT demonstrated a significant improvement in target-to-normal organ ratios of absorbed radiation compared with directly radiolabeled bivalent antibody (conventional radioimmunotherapy [RIT]). Radio-DOTA-biotin administered 48 hours after anti-CD45 streptavidin fusion protein (FP) [BC8 (scFv)4SA] produced markedly lower concentrations of radiation in nontarget tissues compared with conventional RIT. PRIT generated superior target:normal organ ratios in the blood, lung, and liver (10.3:1, 18.9:1, and 9.9:1, respectively) compared with the conventional RIT controls (2.6:1, 6.4:1, and 2.9:1, respectively). The FP demonstrated superior retention in target tissues relative to comparable directly radiolabeled bivalent anti-CD45 RIT. The time point of administration of the second step radiolabeled ligand (radio-DOTA-biotin) significantly impacted the biodistribution of radioactivity in target tissues. Rapid clearance of the FP from the circulation rendered unnecessary the addition of a synthetic clearing agent in this model. These results support proceeding to anti-CD45 PRIT clinical trials for patients with both leukemia and lymphoma.

scholarly journals PrimaTB STAT-PAK Assay, a Novel, Rapid Lateral-Flow Test for Tuberculosis in Nonhuman Primates

2007 ◽  
Vol 14 (9) ◽  
pp. 1158-1164 ◽  
Author(s):  
Konstantin P. Lyashchenko ◽  
Rena Greenwald ◽  
Javan Esfandiari ◽  
David Greenwald ◽  
Carol A. Nacy ◽  
...  
Keyword(s):  
Macaca Fascicularis ◽  
Nonhuman Primates ◽  
Tuberculin Test ◽  
Lateral Flow ◽  
Antibody Responses ◽  
Bacterial Disease ◽  
Flow Test ◽  
Immunodominant Antigens ◽  
Lateral Flow Test ◽  
Cercopithecus Aethiops Sabaeus

ABSTRACT Tuberculosis (TB) is the most important zoonotic bacterial disease in nonhuman primates (NHP). The current diagnostic method, the intradermal palpebral tuberculin test, has serious shortcomings. We characterized antibody responses in NHP against Mycobacterium tuberculosis to identify immunodominant antigens and develop a rapid serodiagnostic test for TB. A total of 422 NHP were evaluated, including 243 rhesus (Macaca mulatta), 46 cynomolgus (Macaca fascicularis), and 133 African green (Cercopithecus aethiops sabaeus) monkeys at five collaborative centers. Of those, 50 monkeys of the three species were experimentally inoculated with M. tuberculosis. Antibody responses were monitored every 2 to 4 weeks for up to 8 months postinfection by MultiAntigen Print ImmunoAssay with a panel of 12 recombinant antigens. All of the infected monkeys produced antibodies at various levels and with different antigen recognition patterns. ESAT-6 and MPB83 were the most frequently recognized proteins during infection. A combination of selected antigens which detected antibodies in all of the infected monkeys was designed to develop the PrimaTB STAT-PAK assay by lateral-flow technology. Serological evaluation demonstrated high diagnostic sensitivity (90%) and specificity (99%). The highest rate of TB detection was achieved when the skin test was combined with the PrimaTB STAT-PAK kit. This novel immunoassay provides a simple, rapid, and accurate test for TB in NHP.

Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): reproductive performance and birth outcome

2004 ◽  
Vol 26 (5) ◽  
pp. 639-650 ◽  
Author(s):  
Thomas M Burbacher ◽  
Kimberly S Grant ◽  
Danny D Shen ◽  
Lianne Sheppard ◽  
Doris Damian ◽  
...  
Keyword(s):  
Reproductive Performance ◽  
Macaca Fascicularis ◽  
Nonhuman Primates ◽  
Birth Outcome

Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): Exposure and toxicokinetics prior to and during pregnancy

2004 ◽  
Vol 26 (2) ◽  
pp. 201-221 ◽  
Author(s):  
Thomas M. Burbacher ◽  
Danny D. Shen ◽  
Bojan Lalovic ◽  
Kimberly S. Grant ◽  
Lianne Sheppard ◽  
...  
Keyword(s):  
Macaca Fascicularis ◽  
Nonhuman Primates

scholarly journals Berberine-Loaded Liposomes for the Treatment of Leishmania infantum-Infected BALB/c Mice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 858 ◽  
Author(s):  
Alba Calvo ◽  
Esther Moreno ◽  
Esther Larrea ◽  
Carmen Sanmartín ◽  
Juan Manuel Irache ◽  
...  
Keyword(s):  
Parasite Burden ◽  
Isoquinoline Alkaloid ◽  
Free Drug ◽  
Immunomodulatory Activity ◽  
Drug Concentrations ◽  
Ic50 Values ◽  
Mean Size ◽  
Rapid Clearance ◽  
Selective Delivery

Berberine (BER)—an anti-inflammatory quaternary isoquinoline alkaloid extracted from plants—has been reported to have a variety of biologic properties, including antileishmanial activity. This work addresses the preparation of BER-loaded liposomes with the aim to prevent its rapid liver metabolism and improve the drug selective delivery to the infected organs in visceral leishmaniasis (VL). BER liposomes (LP-BER) displayed a mean size of 120 nm, negative Z-potential of −38 mV and loaded 6 nmol/μmol lipid. In vitro, the loading of BER in liposomes enhanced its selectivity index more than 7-fold by decreasing its cytotoxicity to macrophages. In mice, LP-BER enhanced drug accumulation in the liver and the spleen. Consequently, the liposomal delivery of the drug reduced parasite burden in the liver and spleen by three and one logarithms (99.2 and 93.5%), whereas the free drug only decreased the infection in the liver by 1-log. The organ drug concentrations—far from IC50 values— indicate that BER immunomodulatory activity or drug metabolites also contribute to the efficacy. Although LP-BER decreased 10-fold—an extremely rapid clearance of the free drug in mice—the value remains very high. Moreover, LP-BER reduced plasma triglycerides levels.

Comparison of anti-CD20 and anti-CD45 antibodies for conventional and pretargeted radioimmunotherapy of B-cell lymphomas

Blood ◽  
2003 ◽  
Vol 101 (6) ◽  
pp. 2340-2348 ◽  
Author(s):  
John M. Pagel ◽  
Nathan Hedin ◽  
Krishnan Subbiah ◽  
Damon Meyer ◽  
Robert Mallet ◽  
...  
Keyword(s):  
Tumor Uptake ◽  
Tetraacetic Acid ◽  
Athymic Mice ◽  
Normal Organ ◽  
Non Hodgkin Lymphoma ◽  
Antibody Conjugate ◽  
Pretargeted Radioimmunotherapy ◽  
Anti Cd20 ◽  
Yttrium 90 ◽  
Cd20 Antibodies

Radiolabeled anti-CD20 antibodies produce responses in 60% to 95% of patients with relapsed non-Hodgkin lymphoma (NHL); however, absorbed radiation ratios between tumors and normal organs are relatively low, and many patients have relapses. In this study we compared the abilities of anti-CD45 (BC8) and anti-CD20 (1F5) antibodies to target human Ramos lymphoma xenografts in athymic mice. When direct radioiodination was performed with conventional methods, BC8 delivered 2- to 4-fold more radioiodine to tumors than 1F5, with tumor-to–normal organ ratios as high as 20:1 using radiolabeled BC8 compared with a maximal ratio of 9.8:1 using radioiodinated 1F5. To optimize the biodistribution of radioactivity, we performed studies following a pretargeting method using streptavidin (SA)–conjugated BC8 and 1F5. Injection of a synthetic clearing agent decreased the circulating level of conjugates by 80% to 90% within 1 hour. Pretargeting with BC8-SA resulted in a 2- to 4-fold greater tumor uptake of radiolabeled biotin than with 1F5-SA, with maximal tumor-to–normal organ ratios of more than 80:1 and approximately 16:1, respectively. Therapy experiments demonstrated that 400 μCi (14.8 MBq) or more of yttrium-90-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)–biotin cured 100% of mice treated with BC8-SA and more than 90% of mice pretargeted with 1F5-SA, with complete remission occurring 8 to 10 days sooner in mice receiving BC8-SA. After treatment with 200 μCi (7.4 MBq) 90Y-DOTA-biotin, 70% of the mice treated with BC8-SA were cured, but no mice were cured using 1F5-SA. Doses up to 800 μCi (29.6 MBq) 90Y-DOTA-biotin were delivered with minor toxicity using either antibody conjugate. These lymphoma xenograft data suggest that pretargeted radioimmunotherapy using either anti-CD20 or anti-CD45 conjugates is highly effective and minimally toxic.

scholarly journals Therapeutic Advantage of Pretargeted Radioimmunotherapy Using a Recombinant Bispecific Antibody in a Human Colon Cancer Xenograft

2005 ◽  
Vol 11 (21) ◽  
pp. 7879-7885 ◽  
Author(s):  
Habibe Karacay ◽  
Pierre-Yves Brard ◽  
Robert M. Sharkey ◽  
Chien-Hsing Chang ◽  
Edmund A. Rossi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Bispecific Antibody ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Therapeutic Advantage ◽  
Pretargeted Radioimmunotherapy

scholarly journals Liposomal Antioxidants for Protection against Oxidant-Induced Damage

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Zacharias E. Suntres
Keyword(s):  
Cell Structure ◽  
Cellular Systems ◽  
Amphiphilic Molecules ◽  
Significant Damage ◽  
Rapid Clearance ◽  
Selective Delivery ◽  
High Concentrations ◽  
Structure And Functions ◽  
Pass Metabolism

Reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions.In vitrostudies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress.

scholarly journals Development of a monkey avatar to study social perception in macaques

2019 ◽  
Author(s):  
Vanessa A.D. Wilson ◽  
Carolin Kade ◽  
Sebastian Moeller ◽  
Stefan Treue ◽  
Igor Kagan ◽  
...  
Keyword(s):  
Macaca Fascicularis ◽  
Nonhuman Primates ◽  
Rhesus Macaques ◽  
Future Research ◽  
Uncanny Valley ◽  
Overt Attention ◽  
Cognitive Studies ◽  
The Uncanny ◽  
Further Development ◽  
Shed Light

AbstractFollowing the expanding use and applications of virtual reality in every-day life, dynamic virtual stimuli are of increasing interest in cognitive studies. They allow for control of features such as gaze, expression and movement, which may help to overcome limitations of using either static or poorly controlled real stimuli. In using virtual stimuli however, one must be careful to avoid the uncanny valley effect - where realistic stimuli can be perceived as eerie, and induce an aversion response. At the same time, it is important to establish whether responses to virtual stimuli mirror responses to depictions of a real conspecific. In the current study, we describe the development of a new avatar with realistic features for nonhuman primates, the ‘primatar’. As a first step towards validation, we assessed how monkeys respond to images of this avatar compared to images of real monkeys, and an unrealistic avatar. We also compared responses between original images and scrambled as well as obfuscated versions of these images. We measured looking time to images in six free moving long-tailed macaques (Macaca fascicularis) and eye movement exploration behaviour in three rhesus macaques (Macaca mulatta). Both groups showed more of such signs of overt attention to original images than scrambled or obfuscated images. In addition, we assessed whether the realistic avatar created an uncanny valley effect through decreased looking time, finding that in both groups, monkeys did not differentiate between real, realistic or unrealistic images. These results provide support for further development of our avatar for use in social cognition studies, and more generally for cognitive research with virtual stimuli in nonhuman primates. Future research needs to shed light on the source of the inconsistent findings for the uncanny valley effect in macaques, to elucidate the roots of this mechanism in humans.

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