Breaking News
December 16, 2018 - Sex work criminalization linked to incidences of violence finds study
December 16, 2018 - Johns Hopkins researchers discover swarming behavior in fish-dwelling parasite
December 16, 2018 - Schistosomiasis prevention and treatment could help control HIV
December 16, 2018 - Early postpartum opioids linked with persistent usage
December 16, 2018 - Johns Hopkins researchers identify molecular causes of necrotizing enterocolitis in preemies
December 16, 2018 - Advanced illumination expands capabilities of light-sheet microscopy
December 16, 2018 - Alzheimer’s could possibly be spread via contaminated neurosurgery
December 16, 2018 - Unraveling the complexity of cancer biology can prompt new avenues for drug development
December 16, 2018 - Inflammatory Bowel Disease, Prostate Cancer Linked
December 16, 2018 - Cannabis youth prevention strategy should target mental wellbeing
December 15, 2018 - Recent developments and challenges in hMAT inhibitors
December 15, 2018 - Sewage bacteria found lurking in Hudson River sediments
December 15, 2018 - CDC selects UMass Amherst biostatistician model that helps predict influenza outbreaks
December 15, 2018 - Researchers reveal brain mechanism that drives itch-evoked scratching behavior
December 15, 2018 - New computer model helps predict course of the disease in prostate cancer patients
December 15, 2018 - Obesity to Blame for Almost 1 in 25 Cancers Worldwide
December 15, 2018 - How the brain tells you to scratch that itch
December 15, 2018 - New findings could help develop new immunotherapies against cancer
December 15, 2018 - World’s largest AI-powered medical research network launched by OWKIN
December 15, 2018 - Young people suffering chronic pain battle isolation and stigma as they struggle to forge their identities
December 15, 2018 - Lifespan extension at low temperatures depends on individual’s genes, study shows
December 15, 2018 - New ingestible capsule can be controlled using Bluetooth wireless technology
December 15, 2018 - Researchers uncover microRNAs involved in the control of social behavior
December 15, 2018 - Research offers hope for patients with serious bone marrow cancer
December 15, 2018 - Link between poverty and obesity is only about 30 years old, study shows
December 15, 2018 - Mass spectrometry throws light on old case of intentional heavy metal poisoning
December 15, 2018 - BeyondSpring Announces Phase 3 Study 105 of its Lead Asset Plinabulin for Chemotherapy-Induced Neutropenia Meets Primary Endpoint at Interim Analysis
December 15, 2018 - Study finds that in treating obesity, one size does not fit all
December 15, 2018 - Tenacity and flexibility help maintain psychological well-being, mobility in older people
December 15, 2018 - Study reveals role of brain mechanism in memory recall
December 15, 2018 - High levels of oxygen encourage the brain to remain in deep, restorative sleep
December 15, 2018 - Experimental HIV vaccine strategy works in non-human primates, research shows
December 15, 2018 - Genetically modified pigs could limit replication of classical swine fever virus, study shows
December 15, 2018 - FDA Approves Herzuma (trastuzumab-pkrb), a Biosimilar to Herceptin
December 15, 2018 - Cost and weight-loss potential matter most to bariatric surgery patients
December 15, 2018 - Cancer Research UK and AstraZeneca open new Functional Genomics Centre
December 15, 2018 - New research lays out potential path for treatment of Huntington’s disease
December 15, 2018 - Prestigious R&D 100 Award presented to Leica Microsystems
December 15, 2018 - Study shows septin proteins detect and kill gut pathogen, Shigella
December 15, 2018 - Study sheds new light on disease-spreading mosquitoes
December 15, 2018 - 2017 Saw Slowing in National Health Care Spending
December 15, 2018 - Monitoring movement reflects efficacy of mandibular splint
December 15, 2018 - Study supports BMI as useful tool for assessing obesity and health
December 15, 2018 - Self-guided, internet-based therapy platforms effectively reduce depression
December 15, 2018 - Organically farmed food has bigger climate impact than conventional food production
December 15, 2018 - Faster, cheaper test has potential to enhance prostate cancer evaluation
December 15, 2018 - Researchers study abnormal blood glucose levels of patients after hospital discharge
December 15, 2018 - Swedish scientists explore direct association of dementia and ischemic stroke deaths
December 15, 2018 - Study finds 117% increase in number of dementia sufferers in 26 years
December 15, 2018 - Eczema Can Drive People to Thoughts of Suicide: Study
December 15, 2018 - Link between neonatal vitamin D deficiency and schizophrenia confirmed
December 15, 2018 - Nurse denied life insurance because she carries naloxone
December 15, 2018 - Ritalin drug affects organization of pathways that build brain networks used in attention, learning
December 15, 2018 - Research pinpoints two proteins involved in creation of stem cells
December 15, 2018 - Gut bacteria may modify effectiveness of anti-diabetes drugs
December 15, 2018 - A new type of ‘painless’ adhesive for biomedical applications
December 15, 2018 - Early physical therapy associated with reduction in opioid use
December 15, 2018 - Breast cancer protection from pregnancy begins many decades later, study finds
December 15, 2018 - How often pregnant women follow food avoidance strategy to prevent allergy in offspring?
December 15, 2018 - Using machine learning to predict risk of developing life-threatening infections
December 15, 2018 - How imaginary friends could boost children’s development
December 15, 2018 - Folate deficiency creates more damaging chromosomal abnormalities than previously known
December 15, 2018 - Study provides new insights into molecular mechanisms underlying role of amyloid in Alzheimer’s disease
December 15, 2018 - For the asking, a check is in the mail to help pay for costly drugs
December 15, 2018 - UA scientists uncover biological processes leading to rare brain disorder in babies
December 15, 2018 - The largest database on industrial poisons
December 15, 2018 - ESMO Immuno-Oncology Congress showcases novel technologies set to benefit many cancer patients
December 15, 2018 - Ovid Therapeutics Announces Plans to Move into a Phase 3 Trial in Pediatric Patients Based on End-of-Phase 2 Meeting for OV101 in Angelman Syndrome
December 15, 2018 - Left ventricular noncompaction – Genetics Home Reference
December 15, 2018 - Children’s sleep not significantly affected by screen time, new study finds
December 15, 2018 - When should dementia patients stop driving? A new guidance for clinicians
December 15, 2018 - Researchers use INTEGRA’s VIAFLO 96/384 to streamline the experimental workflow
December 15, 2018 - Researchers discover protein involved in nematode stress response
December 15, 2018 - Cancer patients have greater risk of developing shingles, study shows
December 14, 2018 - UAlberta scientists identify biomarkers for detecting Alzheimer’s disease in saliva samples
December 14, 2018 - Study uncovers link between tube travel and spread of flu-like illnesses
December 14, 2018 - Caffeine plus another compound in coffee may fight Parkinson’s disease
December 14, 2018 - GW researchers review studies on treatments for prurigo nodularis
December 14, 2018 - Lack of peds preventive care ups unplanned hospital admissions
December 14, 2018 - Miscarriage: When Language Deepens Pain
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