scholarly journals Arsenic-72, 77 as a matched pair radiopharmaceutical for imaging and radiotherapy

2018 ◽  
Author(s):  
◽  
Yutian Feng
Keyword(s):  
Physical Properties ◽  
Half Life ◽  
Operation Time ◽  
Matched Pair ◽  
Generator Column ◽  
Bombesin Receptor ◽  
Targeting Peptide ◽  
High Yields ◽  
No Carrier Added

Radiopharmaceuticals deliver radionuclides to specific target sites via the bifunctional chelate approach, where the radionuclides are chelated with a ligand and linked to a targeting biomolecule. They can be categorized as imaging or therapeutic agents based on the physical properties of the radionuclides. Matched pair radionuclides have advantages because of identical chemistry of the imaging and therapy counterparts and true matched pair radionuclides are rare (e.g., 64,67Cu, 44,47Sc, 135,131I). Radioimmunoimaging and therapy commonly use antibodies (or antibody fragments) as targeting biomolecules, and may take a few days to accumulate in tumor cells. Thus they require radionuclides with longer half-lives. Arsenic-72 ([beta]+, 26 hour half-life) and 77As ([beta]- emitter, 38.8 hour half-life) have suitable physical properties as a true matched pair for radioimaging and therapy. This dissertation focuses on the development of 72,77As matched pair for potential PET imaging and radiotherapy. ... The production and separation of no carrier added (nca) 72,77As will be discussed in Chapter 2. No carrier added 77As separation was improved based on the reported method by decreasing the operation time and increasing capacity based on reported method.[1] The parameters for a 72Se/72As generator were evaluated and nca 72Se was produced via the 70Ge([alpha], 2n)72Se nuclear reaction, separated and loaded onto a generator column. Further evaluations are underway. Radiochemistry of nca 72,77As will be discussed in Chapters 3 and 4 since two chelating approaches were evaluated. The aryl dithiol approach incorporates an aryl ring to nca radioarsenic and complexes it with dithiol ligands. After various modifications and optimizations, radiolabeling nca 72,77As affording dithioarylarsines were accomplished in high yields. The trithiol approach complexes nca 72,77As with a trithiol chelate. Its in vivo stability was evaluated by conjugating the trithiol chelate to a Bombesin receptor targeting peptide and investigating its biodistribution in normal mice. An improved trithiol chelate was proposed and synthesized based on the high in vivo stability but poor targeting efficacy of the initial trithiol complex.

A facile methodology for the synthesis and detection of N7-guanine adduct of sulfur mustard as a biomarker

2002 ◽  
Vol 80 (5) ◽  
pp. 504-509 ◽  
Author(s):  
Mula Kameswara Rao ◽  
Pinaki S Bhadury ◽  
Mamta Sharma ◽  
Rajinder S Dangi ◽  
Appanabhotla S Bhaskar ◽  
...  
Keyword(s):  
Physical Properties ◽  
Spectral Data ◽  
Convenient Method ◽  
Sulfur Mustard ◽  
2D Nmr ◽  
High Yields

A simple and convenient method has been developed for the synthesis of a N7-guanine adduct of sulfur mustard (SM), which can serve as an efficient biomarker for alleged exposure to SM. The adduct obtained in high yields (~78%) was characterized on the basis of its physical properties and spectral data. In addition, HPLC and LC-MS conditions have been standardized for the detection of the adduct in both in vitro and in vivo samples, which is useful for retrospective detection of exposure to SM in biological samples.Key words: sulfur mustard, biomarker, N7-guanine adduct, in vitro, in vivo, HPLC, LC-MS, electrospray, 2D NMR.

scholarly journals Designed ferritin nanocages displaying trimeric TRAIL and tumor-targeting peptides confer superior anti-tumor efficacy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jae Do Yoo ◽  
Sang Mun Bae ◽  
Junyoung Seo ◽  
In Seon Jeon ◽  
Sri Murugan Poongkavithai Vadevoo ◽  
...  
Keyword(s):  
Half Life ◽  
Tumor Targeting ◽  
Threefold Axis ◽  
Apoptosis Pathway ◽  
Cancer Models ◽  
Promising Target ◽  
Extrinsic Apoptosis ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide

AbstractTRAIL is considered a promising target for cancer therapy because it mediates activation of the extrinsic apoptosis pathway in a tumor-specific manner by binding to and trimerizing its functional receptors, DR4 or DR5. Although recombinant human TRAIL has shown high potency and specificity for killing cancer cells in preclinical studies, it has failed in multiple clinical trials for several reasons, including a very short half-life mainly caused by instability of the monomeric form of TRAIL and rapid renal clearance of the off-targeted TRAIL. To overcome such obstacles, we developed a TRAIL-active trimer nanocage (TRAIL-ATNC) that presents the TRAIL ligand in its trimer-like conformation by connecting it to a triple helix sequence that links to the threefold axis of the ferritin nanocage. We also ligated the tumor-targeting peptide, IL4rP, to TRAIL-ATNC to enhance tumor targeting. The developed TRAIL-ATNCIL4rP showed enhanced agonistic activity compared with monomeric TRAIL. The in vivo serum half-life of TRAIL-ATNCIL4rP was ~ 16-times longer than that of native TRAIL. As a consequence of these properties, TRAIL-ATNCIL4rP exhibited efficacy as an anti-tumor agent in vivo against xenograft breast cancer as well as orthotopic pancreatic cancer models, highlighting the promise of this system for development as novel therapeutics against cancer.

scholarly journals Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 521
Author(s):  
Shuang Yin ◽  
Yan Wang ◽  
Bingyang Zhang ◽  
Yiran Qu ◽  
Yongdong Liu ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Half Life ◽  
Tumor Targeting ◽  
Drug Carrier ◽  
Life Extension ◽  
Sprague Dawley ◽  
Functional Peptides ◽  
Targeting Peptide

Ferritin, one of the most investigated protein nanocages, is considered as a promising drug carrier because of its advantageous stability and safety. However, its short half-life and undesirable tumor targeting ability has limited its usage in tumor treatment. In this work, two types of functional peptides, half-life extension peptide PAS, and tumor targeting peptide RGDK (Arg-Gly-Asp-Lys), are inserted to human heavy-chain ferritin (HFn) at C-terminal through flexible linkers with two distinct enzyme cleavable sites. Structural characterizations show both HFn and engineered HFns can assemble into nanoparticles but with different apparent hydrodynamic volumes and molecular weights. RGDK peptide enhanced the internalization efficiency of HFn and showed a significant increase of growth inhibition against 4T1 cell line in vitro. Pharmacokinetic study in vivo demonstrates PAS peptides extended ferritin half-life about 4.9 times in Sprague Dawley rats. RGDK peptides greatly enhanced drug accumulation in the tumor site rather than in other organs in biodistribution analysis. Drug loaded PAS-RGDK functionalized HFns curbed tumor growth with significantly greater efficacies in comparison with drug loaded HFn.

The Infection of Cells by Bullet-Shaped Viruses

1969 ◽  
Vol 27 ◽  
pp. 372-373
Author(s):  
Frederick A. Murphy ◽  
Alyne K. Harrison ◽  
Sylvia G. Whitfield
Keyword(s):  
Electron Microscopy ◽  
Physical Properties ◽  
Host Cell ◽  
Thin Section ◽  
Cultured Cells ◽  
Cell Infection ◽  
Thin Section Electron Microscopy ◽  
Section Electron ◽  
Section Electron Microscopy

The bullet-shaped viruses are currently classified together on the basis of similarities in virion morphology and physical properties. Biologically and ecologically the member viruses are extremely diverse. In searching for further bases for making comparisons of these agents, the nature of host cell infection, both in vivo and in cultured cells, has been explored by thin-section electron microscopy.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

Half-Life of Platelet Factor 4 (PF-4) in Plasma and Platelets from Macaca Mulatta

1977 ◽  
Vol 37 (01) ◽  
pp. 073-080 ◽  
Author(s):  
Knut Gjesdal ◽  
Duncan S. Pepper
Keyword(s):  
Macaca Mulatta ◽  
Half Life ◽  
Human Platelet ◽  
Gel Filtration ◽  
Platelet Factor 4 ◽  
Active Protein ◽  
Platelet Factor ◽  
Membrane Bound

SummaryHuman platelet factor 4 (PF-4) showed a reaction of complete identity with PF-4 from Macaca mulatta when tested against rabbit anti-human-PF-4. Such immunoglobulin was used for quantitative precipitation of in vivo labelled PF-4 in monkey serum. The results suggest that the active protein had an intra-platelet half-life of about 21 hours. In vitro 125I-labelled human PF-4 was injected intravenously into two monkeys and isolated by immuno-precipita-tion from platelet-poor plasma and from platelets disrupted after gel-filtration. Plasma PF-4 was found to have a half-life of 7 to 11 hours. Some of the labelled PF-4 was associated with platelets and this fraction had a rapid initial disappearance rate and a subsequent half-life close to that of plasma PF-4. The results are compatible with the hypothesis that granular PF-4 belongs to a separate compartment, whereas membrane-bound PF-4 and plasma PF-4 may interchange.

Turnover of Human Extrinsic (Tissue-Type) Plasminogen Activator in Rabbits

1981 ◽  
Vol 46 (03) ◽  
pp. 658-661 ◽  
Author(s):  
C Korninger ◽  
J M Stassen ◽  
D Collen
Keyword(s):  
Plasminogen Activator ◽  
Intravenous Injection ◽  
Active Site ◽  
Half Life ◽  
Degradation Products ◽  
Gel Filtration ◽  
Tissue Type ◽  
Organ Distribution ◽  
Small Rise

SummaryThe turnover of highly purified human extrinsic plasminogen activator (EPA) (one- and two-chain form) was studied in rabbits. Following intravenous injection, EPA-activity declined rapidly. The disappearance rate of EPA from the plasma could adequately be described by a single exponential term with a t ½ of approximately 2 min for both the one-chain and two-chain forms of EPA.The clearance and organ distribution of EPA was studied by using 125I-labeled preparations. Following intravenous injection of 125I-1abeled EPA the radioactivity disappeared rapidly from the plasma also with a t ½ of approximately 2 min down to a level of 15 to 20 percent, followed by a small rise of blood radioactivity. Gel filtration of serial samples revealed that the secondary increase of the radioactivity was due to the reappearance of radioactive breakdown products in the blood. Measurement of the organ distribution of 125I at different time intervals revealed that EPA was rapidly accumulated in the liver, followed by a release of degradation products in the blood.Experimental hepatectomy markedly prolonged the half-life of EPA in the blood. Blocking the active site histidine of EPA had no effect on the half-life of EPA in blood nor on the gel filtration patterns of 125I in serial plasma samples.It is concluded that human EPA is rapidly removed from the blood of rabbits by clearance and degradation in the liver. Recognition by the liver does not require a functional active site in the enzyme. Neutralization in plasma by protease inhibitors does not represent a significant pathway of EPA inactivation in vivo.

Clearance and In Vivo Release by Heparin of Human Platelet Factor 4 (PF4) in the Rabbit

1984 ◽  
Vol 52 (02) ◽  
pp. 157-159 ◽  
Author(s):  
M Prosdocimi ◽  
N Scattolo ◽  
A Zatta ◽  
F Fabris ◽  
F Stevanato ◽  
...  
Keyword(s):  
Half Life ◽  
Human Platelet ◽  
Slow Component ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
In Vivo Release ◽  
Partial Release ◽  
Different Doses ◽  
New Zealand Rabbits

Summary13 male New Zealand rabbits were injected with two different doses (25 μg/Kg and 100 μg/Kg) of human platelet factor 4 antigen (PF4). The disappearance of the protein was extremely fast with an half-life for the fast component of 1.07 ± 0.16 and 1.76 ± 0.11 min respectively. The half-life for the slow component, detectable only with the highest dosage, was 18.8 min.The administration of 2500 I.U. of heparin 30 min after PF4 administration induced a partial release of the injected protein and its clearance from plasma was slow, with half-life of 23.3 ± 5.9 min and 30.9 ± 2.19 min respectively.

(Preprint)

2018 ◽  
Author(s):  
Dr Malathi Dayalan ◽  
Dr Sudeshna Sharma ◽  
Dr Shweta Poovani ◽  
Dr Saher Altaf
Keyword(s):  
Myofascial Pain ◽  
Mouth Opening ◽  
Masticatory Muscles ◽  
Matched Pair ◽  
Masticatory Muscle ◽  
Muscle Disorders ◽  
Occlusal Contact ◽  
Group I ◽  
Group Ii

BACKGROUND Masticatory system is a complex functional unit, primarily engaged in chewing, swallowing and breathing functions, and some parts are involved in taste recognition and determination of food consistency. Sophisticated functional performances of speech and emotional expressions are specifically human qualities. Irregularities in occlusion appears to be the precipitating factor in the pathogenesis of myofascial pain dysfunction syndrome. Tek- Scan III records the bite length, number, distribution, timing, duration and the relative force of each tooth contact. It also records the sequence of occlusal contacts in terms of time and the associated force with each occlusal contact. The aim of this study was to treat masticatory muscle disorders with occlusal equilibration, and compare the efficacy of treatment outcomes between selective grinding and stabilization splints using Tek-Scan III. OBJECTIVE Objective of this study was to compare the efficacy of occlusal equilibration achieved through selective griding and stabilization splints using Tek-Scan III. METHODS In this in vivo study, 40 patients with masticatory muscle disorders were selected based on the inclusion and exclusion criteria. The occlusal discrepancies were analyzed using Tek-Scan III. The selected 40 subjects were then randomly divided into 2 groups based on the treatment they recieved; Group I – Selective grinding group (20) and Group II – Stabilization splint group (20). Comparison of pre-treatment and post treatment results were evaluated in terms of pain, mouth opening, left and right side force percentage as recorded through Tek-Scan III and reduction of disclusion time. Statistical analysis was carried out with Kolmogorov Smirnov test, Wilcoxon matched pair test and Mann-Whitney U test. RESULTS Wilcoxon matched pairs test demonstrated that there was statistically significant results ( p = 0.0007) in both the groups for reduction of disclusion time, elimination of pain and improved mouth opening. Patients in Group I showed better results as compared to Group II in terms of disclusion time, pain and mouth opening. CONCLUSIONS Occlusal equilibration brought about by reducing the disclusion time using the Tek- Scan III reduced the symptoms of pain in masticatory muscles. Patients in group I (Selective grinding) however showed better results when compared to patients in group II (Stabilization splints).

scholarly journals Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Click Reaction ◽  
Chemotherapy Drugs ◽  
Targeting Peptide ◽  
And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

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