Compounds 1-4 were synthesized and investigated for selectivity and potency for the oxytocin receptor (OTR) to determine their viability as radioactive ligands. Binding assays determined 1-4 to have high binding affinity for both the human and rodent OTR and also have high selectivity for the human OTR over human vasopressin V1a receptors (V1aR). Inadequate selectivity for OTR over V1aR was found for rodent receptors in all four compounds. The radioactive (C-11, F-18, and I-125) derivatives of 1-4 were synthesized and investigated for use as autoradiography and positron emission tomography (PET) ligands. Receptor autoradiography performed with [(125)I]1 and [(125)I]2 on rodent brain slices provided the first small molecule radioligand images of the OTR and V1aR. Biodistribution studies determined [(125)I]1 and [(125)I]2 were adequate for in vivo peripheral investigations, but not for central investigations due to low uptake within the brain. A biodistribution study with [(18)F]3 suggested brain uptake occurred slowly over time. PET imaging studies with [(18)F]3 and [(11)C]4 using a rat model provided insufficient uptake in the brain over a 90 and 45 min scan times respectively to merit further investigations in non-human primates.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701955 | PMC |
| http://dx.doi.org/10.1016/j.bmc.2012.02.019 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Metabolite Study and Structural Authentication for the First-in-Human Use Sphingosine-1-phosphate Receptor 1 Radiotracer.
ACS Chem Neurosci
May 2024
Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri 63110, United States.
Article Synopsis
- The study investigates the S1PR1 radiotracer [C], which shows potential in PET imaging for neuroinflammation in multiple sclerosis, focusing on identifying and characterizing its radiometabolites in human and animal studies.
- It highlights the challenge posed by a specific lipophilic radiometabolite that crosses the blood-brain barrier, complicating the quantitative analysis of neuroimaging results.
- The researchers authenticated the structure of this radiometabolite through detailed analysis, confirming its identity as -oxide, and demonstrated that this metabolite does not penetrate brain tissue in experimental rats and primates.
Automated radiolabeling and handling of Lu- and Ac-PSMA-617 using a robotic pipettor.
J Labelled Comp Radiopharm
March 2024
Molecular Cancer Imaging Facility, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
While automated modules for F-18 and C-11 radiosyntheses are standardized with features such as multiple reactors, vacuum connection and semi-preparative HPLC, labeling and processing of compounds with radiometals such as Zr-89, Lu-177 and Ac-225 often do not require complex manipulations and are frequently performed manually by a radiochemist. These procedures typically involve transferring solutions to and from vials using pipettes followed by heating of the reaction mixture, and do not require all the features found in most commercial automated synthesis units marketed as F-18 or C-11 modules. Here we present an efficient automated method for performing radiosyntheses involving radiometals by adapting a commercially available robotic pipettor originally developed for high-throughput processing of biological samples.
View Article and Find Full Text PDFRadiochemistry: A Hot Field with Opportunities for Cool Chemistry.
ACS Cent Sci
December 2023
Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, Wisconsin 53706, United States.
Recent Food and Drug Administration (FDA) approval of diagnostic and therapeutic radiopharmaceuticals and concurrent miniaturization of particle accelerators leading to improved access has fueled interest in the development of chemical transformations suitable for short-lived radioactive isotopes on the tracer scale. This recent renaissance of radiochemistry is paired with new opportunities to study fundamental chemical behavior and reactivity of elements to improve their production, separation, and incorporation into bioactive molecules to generate new radiopharmaceuticals. This outlook outlines pertinent challenges in the field of radiochemistry and indicates areas of opportunity for chemical discovery and development, including those of clinically established (C-11, F-18) and experimental radionuclides in preclinical development across the periodic table.
View Article and Find Full Text PDFHigh-Contrast and Fast-Removable F-MRI Labels with Perfluoro-tert-Butyl Substituents.
ChemMedChem
September 2023
Faculty of Physics, Lomonosov Moscow State University, Leninskie Gory 1, bld. 2., 119991, Moscow, Russia.
Article Synopsis
- F-MRI is a non-invasive imaging technique that uses new compounds with perfluoro-tert-butyl groups as labels for tracking biological activity without ionizing radiation.
- The specific compounds tested, 1,2-bis(perfluoro-tert-butoxy)ethane and 1,3-bis(perfluoro-tert-butyl)propane, are made up of 68.67% and 71.25% fluorine atoms, respectively, and showed promising imaging contrast in lab studies.
- These compounds exhibit good biological safety and can be eliminated from the body in about 30 days after administration at a low dose, making them suitable for F-MRI applications.
Greater tau pathology is associated with altered predictive coding.
Brain Commun
August 2022
Specialty of Anaesthetics, University of Sydney, Camperdown, Australia.
Altered predictive coding may underlie the reduced auditory mismatch negativity amplitude observed in patients with dementia. We hypothesized that accumulating dementia-associated pathologies, including amyloid and tau, lead to disturbed predictions of our sensory environment. This would manifest as increased reliance on 'observed' sensory information with an associated increase in feedforward, and decrease in feedback, signalling.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!