Research Article: Effect of pH Variation on Cross-Linking of Water-Soluble and Acid- Soluble Chitosan with Sodium Tripolyphosphate and Gallium-67

Author(s): Narjes D. Kamali, Alireza Alishahi*, Marzieh Heidarieh*, Saeed Rajabifar, Hojat Mirsadeghi and Moazame Kordjazi

Background: Chitosan is a cationic biopolymer obtained from deacetylating chitin, a natural compound present in crustacean shell, fungi and exoskeleton of insects. Chitosan involves various applications, including as drug and gene delivery systems, as wound dressing material and scaffolds for tissue engineering, agriculture, textile, food and feed nanotechnology, and in wastewater treatments. Chitosan-TPP particle has been figured out as the most important and stable nanoparticle for chitosan application in various fields.

Objective: In this study, chitosan was chemically modified by sodium tripolyphosphate (TPP). Afterward, TPP-chitosan was radiolabeled with the gallium-67 radionuclide. The effect of several factors on labeling yield, such as chitosan solubility, acidity and concentration of TPPchitosan solution, and incubation time with gallium-67, were investigated.

Methods: To prepare [⁶⁷Ga] gallium-chitosan complex, chitosan (0.5 ml) was dissolved in 2.2 mCi of [⁶⁷Ga] gallium chloride solution. The obtained solution was stirred for 5 min and then kept for 30 min at room temperature. The radiochemical purity and radiolabeling yield were measured via radiochromatography, which was performed by using a radio thin-layer chromatography (TLC) scanner instrument. To investigate the effect of chitosan kind and concentration on the labeling yield, two kinds of chitosan (acid-soluble chitosan and water-soluble chitosan) at two different concentrations (1% and 0.5%) and different pH were used. In addition, labeling efficiency and stability of the ⁶⁷Ga-TPP-chitosan complex (acidic/water soluble chitosan) at both concentrations (0.5 and 1%) and at room temperature were assessed for 30, 45 and 60 min.

Results: The incubation time did not have any significant effect on labeling yield. The acidic soluble chitosan exhibited the highest radiolabeling yield at pH=9.3-10.4, while water-soluble chitosan showed the highest radiolabeling yield at pH > 5. Also, the prepared complex was stable in the final solution at room temperature and could even be used 24 hours after preparation for further application.

Conclusion: Taken together, the TPP-modified water-soluble chitosan at the concentration of 0.5 % depicted the highest radiochemical yield (>95 %) in the optimized condition (pH= 6.2– 7.6). Therefore, TPP modified water-soluble chitosan can prove to be an effective carrier for therapeutic radionuclides in tumor treatment.

learn more: https://bit.ly/3W0hTjs

Keywords: Chitosan, gallium-67 (⁶⁷Ga), pH, TPP, radiolabeling, water-soluble.

Wishing you a very Happy Birthday | Dr. Sean L. Kitson

Dr. Sean L. Kitson serves as the Editor-in-Chief of the Journal Current Radiopharmaceuticals

Sean L. Kitson
Department of Biocatalysis and Isotope Chemistry Almac Sciences
Almac House
Craigavon
Northern Ireland

Press Release | Dosimetry and toxicity studies of a sulfonamide derivative of Sulforhodamine 101

 

The article by Dr. E Savio et al. is published in Current Radiopharmaceuticals, 2018

BACKGROUND

The SR101 N-(3-[18F]Fluoropropyl) sulfonamide ([18F]SRF101) is a Sulforhodamine 101 (SR101) derivative that was previously synthesised by our group. The fluorescent dye SR101 has been reported as a specific marker of astroglia in the neocortex of rodents in vivo. Some limitations of SR101 with respect to cell specificity have been identified. This derivative was labelled to study its biological in vivo behaviour through PET imaging.

As some recent investigations have shown, astroglia is affected in the early stages of different neurologic diseases, and reactive astrocytes contribute to neuroinflammation at later stages. This investigation focused on reactive astrocytosis in Alzheimer’s disease (AD). It is postulated that [18F]SRF101 is a potential PET radiotracer for astrocytosis detection. A biological characterisation of the novel tracer in a triple-transgenic mice model of AD (3xTg) was performed, and the results were compared with those of healthy Black C57BL6J mice. The biodistribution studies showed a hepatobiliary metabolisation of the compound. PET imaging with [18F]SRF101 revealed that the novel tracer could be a marker of astrocytosis in this animal model. These results suggested that [18F]SRF101 is a promising candidate for a more extensive evaluation as a PET astrocyte tracer.

To conclude the preclinical characterisation of [18F]SRF101 and to allow for drafting a pilot clinical evaluation in patients, radiation dosimetry studies of [18F]SRF101 injections were conducted on mice considering the following issues: i) the absorbed dose assessment can be based on biokinetic data obtained in small animals and ii) to develop new radiotracers for brain imaging, studies have been carried out on time-activity curves in different sections of the brain and in other organs.

A single-dose toxicity study was also carried out considering the guidelines on toxicology studies applicable to radiopharmaceuticals. The toxicological limit chosen in this case was <100 μg based on the concept of microdosing. The study was carried out with a dose set by allometric scaling with a safety factor of 100. Because [18F]SRF101 is a radiopharmaceutical prepared by a not-quantitative radiolabelling reaction and its synthetic procedure involves a purification step to separate the desired radioactive compound from the reaction mixture, toxicity studies were performed for unlabelled SRF101.

In summary, the aim of this study was to perform a toxicological evaluation of [18F]SRF101 and to estimate the human radiation dosimetry of this tracer based on preclinical studies. Obtaining this data will allow for moving forward to assess its potential as a PET imaging radiopharmaceutical for clinical use.

RESULTS

All animals survived until the end of the study with no systemic signs of toxicity throughout the entire observation period. No drug related changes were noted in the parameters examined during the 14-day study, including body weight, food consumption, eyes changes, clinical pathology parameters, gross necropsy findings, absolute and relative organ weights, histopathology findings, or microscopic lesions.

The absorbed and effective doses were estimated by OLINDA/EXM V2.0. Both dosimetric models–male and female–presented the same tendency. The highest total absorbed dose values were for the different sections of the intestines (left colon, small intestine, right colon and rectum). For the male dosimetric model, other organs exhibiting a high total absorbed dose included the liver, kidneys, gallbladder wall and pancreas. For the female dosimetric model, the uterus was added in addition to the mentioned organs.

The effective dose for male and female dosimetric models was 4.03E-03mSv/MBq and 5.08E-03mSv/MBq, respectively. For an administrated activity of 350MBq this would correspond to 1.41mSv and 1.78mSv for the same dosimetric models.

CONCLUSIONS

A toxicological evaluation of SRF101 was performed, which verified the biosafety of the new compound for single-intravenous injections in humans. The dosimetry calculations from the animal data revealed that the radiation-associated risk of [18F]SRF101 would be of the same order as other 18F radiopharmaceuticals used in clinical applications. In summary, the data generated through these studies confirm that the novel radiotracer would be safe for use in human PET imaging. This would allow for drafting a pilot clinical evaluation of patients.

Browse the Article at: http://www.eurekaselect.com/165008

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New Issue :: Current Radiopharmaceuticals 10, Issue 1

Current Radiopharmaceuticals publishes original research articles, letters, reviews, drug clinical trial studies and guest edited issues on all aspects of research and development of radiolabelled compound preparations. The scope of the journal covers the following areas: radio imaging techniques, therapies; preparation and application of radionuclide compounds including the incorporation of tracer methods used in scientific research and applications.

Articles from the journal Current Radiopharmaceuticals 10, Issue 1:

• Radiopharmaceuticals for the Diagnosis and Therapy of Neuroendocrine Differentiated Prostate Cancer
• New Horizons on Molecular Pharmacology Applied to Drug Discovery: When Resonance Overcomes Radioligand Binding
• 177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma
• 99mTc-labeled White Blood Cell Scan as a Guide to Open Biopsy in the Management of Hip and Knee Prosthesis Infection: Preliminary Results
• Development of a Novel Carbon-11 Labeled PET Radioligand for Melanin- Concentrating Hormone Receptor 1
• Synthesis and Preliminary Evaluation of 5-[18F]fluoroleucine
• Development of a Radiolabeled Amlodipine Analog for L-type Calcium Channel Imaging
• A Sensitive Method for the Measurement of Copper at Trace Levels Using an HPLC-Based Assay
• Evaluation of the Influence of the Conjugation Site of the Chelator Agent HYNIC to GLP1 Antagonist Radiotracer for Insulinoma Diagnosis

                    For details on the articles, please visit this link :: http://bit.ly/2pBOwbj

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Current Radiopharmaceuticals publishes original research articles, letters, reviews, drug clinical trial studies and guest edited issues on all aspects of research and development of radiolabelled compound preparations. The scope of the journal covers the following areas: radio imaging techniques, therapies; preparation and application of radionuclide compounds including the incorporation of tracer methods used in scientific research and applications.

Articles from the journal Current Radiopharmaceuticals 9, Issue 3:

• Radiolabeled Sugars Used for PET and SPECT Imaging
• Gallium-68 in Medical Imaging
• Production of 68Ga-citrate Based on a SnO2 Generator for Short-Term Turpentine Oil-Induced Inflammation Imaging in Rats
• Radiosynthesis of [18F]-fluorobenzoate-doxorubicin Using Acylation Approach
• Dual Nuclear/Fluorescence Imaging Potantial of Zinc(II) Phthalocyanine in MIA PaCa-2 Cell Line
• 18F-FDG-PET/CT in Patients Affected by Differentiated Thyroid Carcinoma with Positive Thyroglobulin Level and Negative 131I Whole Body Scan. It’s Value Confirmed by a Bicentric Experience
• Automated PET Radiotracer Manufacture on the BG75 System and Imaging Validation Studies of [18F]fluoromisonidazole ([18F]FMISO)
• 18F-Fluoroestradiol Positron Emission Tomography in Breast Cancer Patients: Systematic Review of the Literature & Meta-Analysis
• Combination Treatment of Glioblastoma by Low-Dose Radiation and Genistein

               For details on the articles, please visit this link :: http://bit.ly/2hU69zz

 

New Issue ::: Current Radiopharmaceuticals , 9 Issue 2

Current Radiopharmaceuticals publishes original research articles, letters, reviews, drug clinical trial studies and guest edited issues on all aspects of research and development of radiolabelled compound preparations. The scope of the journal covers the following areas: radio imaging techniques, therapies; preparation and application of radionuclide compounds including the incorporation of tracer methods used in scientific research and applications.

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• Small-Animal Molecular Imaging for Preclinical Cancer Research: μPET and μSPECT
• Radioguided Surgery for Localization of Nonpalpable Breast Lesions A Mini-Review
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• Convenient and Efficient Method for Quality Control Analysis of 18F-Fluorocholine: For a Small Scale GMP-based Radiopharmaceuticals Laboratory Set-up
• Evaluation of a Labelled Bacteriophage with 99mTc as a Potential Agent for Infection Diagnosis
• Preparation and Administration of I-125 Labeled Seeds for Localization of Nonpalpable Breast Lesions
• Brain Network Underlying the Improvement of Social Functioning in Schizophrenic Patients After One-year Treatment with Social Skills Training
• Preliminary Experience with Yttrium-90-labelled Rituximab (Chimeric Anti CD-20 Antibody) in Patients with Relapsed and Refractory B Cell Non-Hodgkins Lymphoma
• Diagnostic and Prognostic Value of 18F-FDG PET/CT in Male Breast Cancer: Results From a Bicentric Population
• Hypoxia Radiotracer Produced Automatically in Dose-on-Demand Fashion

For details on the articles, please visit this link :: http://bit.ly/2c285zA