Breaking News
October 16, 2018 - New research identifies modifiable dementia risk factor in elderly people
October 16, 2018 - Zebrafish study uncovers molecular ‘brake’ that helps control eye lens development
October 16, 2018 - Overlapping copy number variations underlie autism and schizophrenia in Japanese patients
October 16, 2018 - Majority of Americans’ ancestry can be traced through existing DNA databases
October 16, 2018 - Patients coerced into mental health care less likely to perceive treatment as effective
October 16, 2018 - What you need to know about autism spectrum disorder
October 16, 2018 - Antidepressants can be used to treat Alzheimer’s disease
October 16, 2018 - Study uncovers important role of PRMT1 in dilated cardiomyopathy
October 16, 2018 - Nutritional quality of breakfast linked to cardiovascular and metabolic risk factors in children
October 16, 2018 - Study uses novel approach to investigate genetic origins of mental illnesses
October 16, 2018 - Scientists develop dual anthrax-plague vaccine
October 16, 2018 - Poor Outcomes for Hispanic Infants With Congenital Heart Dz
October 16, 2018 - Global study finds youngest in class more likely to be diagnosed with ADHD
October 16, 2018 - Researchers sequence two selfish genes in the fungus Neurospora intermedia
October 16, 2018 - Survey results highlight the need for better communication between patients and HCPs about bacterial vaginosis
October 16, 2018 - Researchers develop fibrin-targeting immunotherapy to protect against neurodegeneration
October 16, 2018 - Researchers create open access database on healthy immunity
October 16, 2018 - Rice University chemist wins big award to study small surfaces
October 16, 2018 - Study finds 43% drop in stroke rate
October 16, 2018 - Researchers identify basic relationships of cell cycle and cellular senescence in the placenta
October 16, 2018 - UA professor receives NSF grant to develop antifouling materials for medical implants
October 16, 2018 - Obesity Doubles Odds for Colon Cancer in Younger Women
October 16, 2018 - Adults with ADHD not constrained in creativity
October 16, 2018 - Raising visibility for people and students with chronic illness and disability
October 16, 2018 - Allele awarded NIH grant to develop nanoantibody therapies for treatment of sepsis
October 16, 2018 - Only 59% of young adults undergoing surgery are fluid responsive
October 16, 2018 - Research points to potential new treatment for hearing loss
October 16, 2018 - MDI Biological Laboratory receives $1.2 million SEPA grant to promote data literacy
October 16, 2018 - Vast majority of dementia cases may arise from spontaneous genetic errors
October 16, 2018 - New project aims to deliver fast, effective treatment for autoimmune rheumatic diseases
October 16, 2018 - Study identifies molecular switch that controls fate of milk-producing breast cells
October 16, 2018 - Research shows diet has little influence on precursor to gout
October 16, 2018 - “Without Dr. Shumway doing his miracle work, three generations would not be here”: A Stanford heart transplant patient’s story
October 16, 2018 - Non-invasive brain stimulation sheds light on neurobiology underlying implicit bias
October 16, 2018 - Researchers demonstrate integrated technique to control production of cell therapeutics
October 16, 2018 - Breast tomosynthesis detects 34% more tumors than traditional mammography
October 16, 2018 - Rhode Island Hospital, Brown receive $800,000 grant to keep up fight against opioid epidemic
October 16, 2018 - UVA partners with health systems in AVIA network’s Medicaid Transformation Project
October 16, 2018 - Trevena Announces Oliceridine FDA Advisory Committee Meeting Outcome
October 16, 2018 - Study reveals early warning signs of heart problems in patients with newly diagnosed lupus
October 16, 2018 - Connecting the dots of Alzheimer’s disease
October 16, 2018 - New publication offers evidence-based content for global breast imaging medical community
October 16, 2018 - ‘EinsteinVision’ that improves hand-eye coordination of surgeons introduced at Harefield Hospital
October 16, 2018 - WRAIR clinical study evaluates safety and immunogenicity of Marburg vaccine
October 16, 2018 - Ketamine can be considered as alternative to opioids for short-term pain control in ED
October 16, 2018 - Endurance exercise training beneficially alters gut microbiota composition
October 15, 2018 - FDA Approves Yutiq (fluocinolone acetonide intravitreal implant) for Chronic Non-Infectious Posterior Segment Uveitis
October 15, 2018 - Birthing Options for Full-Term Pregnancy
October 15, 2018 - Stressed, toxic, zombie cells seen for first time in Alzheimer’s
October 15, 2018 - Concussion researchers study head motion in high school football hits | News Center
October 15, 2018 - Neuropsychiatric symptoms related to earliest stages of Alzheimer’s brain pathology
October 15, 2018 - Neck collar device may help protect the brain of female high school soccer players
October 15, 2018 - Research reveals how the inner ear processes speech
October 15, 2018 - Many parents still skeptical about safety and effectiveness of flu shot, survey finds
October 15, 2018 - Payer Policies May Discourage Non-Pharma Tx for Low Back Pain
October 15, 2018 - Exercise may delay cognitive decline in people with rare Alzheimer’s disease
October 15, 2018 - Researchers modify CRISPR to reorganize genome | News Center
October 15, 2018 - Innovative brain tumor operation set to tailor to patients’ needs
October 15, 2018 - Findings offer new insight into early changes that occur during AD pathology
October 15, 2018 - Neurons regulating reproductive hormone release have different activity in epileptic mice
October 15, 2018 - More parents are concerned about taking babies swimming in public pools
October 15, 2018 - Health Tip: Know the Risk Factors for Lower Back Pain
October 15, 2018 - Study shows cigarillo flavors enhanced by high-intensity sweeteners
October 15, 2018 - Study traces hospital-acquired bloodstream infections to patients’ own bodies | News Center
October 15, 2018 - Abnormal vision in childhood can affect development of brain areas responsible for attention
October 15, 2018 - Study highlights need for increased support for alcohol-related liver disease patients
October 15, 2018 - Color-changing contact lens could help doctors to monitor eye disease medications
October 15, 2018 - Tobacco heating products cause less staining to teeth than conventional cigarettes
October 15, 2018 - Young adults who are obese can expect to lose up to 10 years in life expectancy
October 15, 2018 - Scientists uncover how proteins meet on the cell membrane
October 15, 2018 - Affordable housing with supportive social services for senior citizens can reduce hospital use
October 15, 2018 - Schiller Easy Pulse Saves Lives
October 15, 2018 - The latest ECG device from Schiller
October 15, 2018 - Following a Tissue Sample
October 15, 2018 - Prisoners need drug and alcohol treatments but AA programs aren’t the answer
October 15, 2018 - Andrea Califano and Jordan Orange Elected to National Academy of Medicine
October 15, 2018 - The impending risk of African Swine Fever Virus
October 15, 2018 - Breastfeeding reduces the number of antibiotic-resistant bacteria in infant gut
October 15, 2018 - Researchers develop comprehensive molecular atlas of postnatal mouse heart development
October 15, 2018 - ObsEva SA Presents Clinical Data from Phase III IMPLANT 2 Trial of Nolasiban in IVF at the American Society of Reproductive Medicine (ASRM) Annual Meeting
Toxicological evaluation and dosimetry estimation of potential PET radiotracer

Toxicological evaluation and dosimetry estimation of potential PET radiotracer

image_pdfDownload PDFimage_print

Background

The SR101 N-(3-[18F]Fluoropropyl) sulfonamide ([18F]SRF101) is a Sulforhodamine 101 (SR101) derivative that was previously synthesized 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 labeled to study its biological in vivo behavior 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 characterization 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 metabolization 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.

Source:

https://benthamscience.com/

Tagged with:

About author

Related Articles