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

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

RECENTLY PUBLISHED ISSUES – BENTHAM SCIENCE JOURNALS

Drug Delivery Letters 7-3

http://bit.ly/2CSTUu5

Mini-Reviews in Medicinal Chemistry 17-17

http://bit.ly/2BrqB17

Mini-Reviews in Medicinal Chemistry 17-18

http://bit.ly/2Cxnwfq

Medicinal Chemistry 13-8

http://bit.ly/2j8h1  rM

Reviews on Recent Clinical Trials 12-3

http://bit.ly/2AU9nZy

Reviews on Recent Clinical Trials 12-4

http://bit.ly/2ARFAAF

Cardiovascular & Hematological Agents in Medicinal Chemistry 15-1

http://bit.ly/2jbxwDi

Current Analytical Chemistry 13-6

http://bit.ly/2kcWeUK

Recent Advances in Electrical & Electronic Engineering 10-3

http://bit.ly/2BFeYGu

Current Radiopharmaceuticals 10-3

http://bit.ly/2ySh28A

recent-issues

Highlighted Article – Radiochemical Evaluation and In Vitro Assessment of the Targeting Ability of a Novel 99mTc-HYNIC-RGD for U87MG Human Brain Cancer Cells – Current Radiopharmaceuticals

CR-Articles_10-3-Nourollah Sadeghzadeh.jpg

To access this article, please visit: http://www.eurekaselect.com/153889

Podcast: Personalized And Precision Medicine In Cancer By Dr. Partha S Choudhury

Author(s): Partha S Choudhury, Manoj Gupta.

For article details, visit: http://www.eurekaselect.com/154535/article

Subscribe our YouTube channelhttp://bit.ly/1lr0czy

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.

crp

Articles from the journal Current Radiopharmaceuticals 10, Issue 1:

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

Highlighted Article for the journal “Current Radiopharmaceuticals”

CR-Articles_9-3- Baljinder Singh

http://benthamscience.com/journals/current-radiopharmaceuticals/

New Issue :: Current Radiopharmaceuticals 9, Issue 3

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.

crp

Articles from the journal Current Radiopharmaceuticals 9, Issue 3:

               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.

Articles from the journal Current Radiopharmaceuticals , 9 Issue 2

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

“Bone Metastases Radiopharmaceuticals: An Overview”

Most Cited Article from the Journal

“Current Radiopharmaceuticals”

1969209_795547127204252_9043461346528902104_nAbstract:

The skeleton is one of the preferential sites for metastases of solid tumors, and metastatic disease is the most common malignancy of the bone. Diagnosis and evaluation of skeletal metastases require more frequently a combined approach of different diagnostic methods. Between the currently available imaging modalities, a major role is devoted to two radionuclide functional techniques namely scintigraphy and positron emission tomography (PET) imaging. Both these techniques require the use of different radiopharmaceuticals. The aim of this paper is to review the most important radiocompounds that can be successfully used to detect and/or characterize bone metastases.

For details, visit: http://benthamscience.com/journals/current-radiopharmaceuticals/volume/6/issue/1/page/41/

%d bloggers like this: