Radiotracer stereochemistry affects substrate affinity and kinetics for improved imaging of system xC– in tumors was written by Greenwood, Hannah E.;Edwards, Richard;Koglin, Norman;Berndt, Mathias;Baark, Friedrich;Kim, Jana;Firth, George;Khalil, Eman;Mueller, Andre;Witney, Timothy H.. And the article was included in Theranostics in 2022.Recommanded Product: 76-83-5 This article mentions the following:
Amino acid utilization is perturbed in cancer cells, which rewire their metabolism to support cell survival and proliferation. This metabolic reprogramming can be exploited for diagnostic purposes through positron emission tomog. imaging of fluorine-18 labeled amino acids. Despite its promise, little is known regarding transporter-recognition of non-natural amino acid stereoisomers or their utility for cancer imaging. We report here the synthesis and in vivo characterization of a radiolabeled amino acid (R)-4-(3-18F-fluoropropyl)-L-glutamate ([18F]FRPG) and compared its tumor imaging properties to the 4S-isomer, [18F]FSPG. [18F]FRPG and [18F]FSPG uptake was assessed in H460 lung cancer cells, with efflux measured 30 min after removal of exogenous activity. Specificity of [18F]FRPG for system xC– was further examined following transporter inhibition and blocking studies with system xC– substrates. [18F]FRPG and [18F]FSPG pharmacokinetics was next quantified in mice bearing s.c. A549, H460, VCAP and PC3 tumors, with mice bearing A549 tumors imaged by PET/CT. To better-understand differential tumor retention, radiometabolite anal. was performed on tissue and blood samples after imaging. Next, [18F]FRPG and [18F]FSPG retention in lipopolysaccharide-treated lungs were compared to an orthotopic H460 lung cancer model. Finally, the sensitivity of [18F]FRPG to manipulation of the redox environment was examined in cell and in vivo models. [18F]FRPG was specifically transported across the plasma membrane by the cystine/glutamate antiporter system xC– and retained at high levels in multiple tumor models. Conversely, [18F]FRPG was rapidly extracted from the blood and cleared from tissues with low system xC– expression. Due to its favorable imaging properties, tumor-to-blood ratios ≥10 were achieved with [18F]FRPG, which were either equal to or greater than [18F]FSPG. In addition, [18F]FRPG retention in orthotopic lung tumors with high system xC– expression was 2.5-fold higher than inflamed tissue, allowing for clear tumor visualization. In vivo, [18F]FRPG and [18F]FSPG were metabolized to a single species, with [18F]FRPG showing a higher percentage of parent radiotracer in tumors compared to [18F]FSPG. [18F]FRPG was sensitive to redox manipulations and tumor retention was reduced following treatment with liposomal doxorubicin in mice bearing ovarian tumors. Given the fast clearance and low background retention of [18F]FRPG throughout the body, this radiotracer holds promise for the imaging of system xC– activity and treatment response monitoring in tumors of the thorax, abdomen, and head and neck. [18F]FRPG PET imaging provides a sensitive noninvasive measure of system xC– and excellent properties for cancer imaging. In the experiment, the researchers used many compounds, for example, (Chloromethanetriyl)tribenzene (cas: 76-83-5Recommanded Product: 76-83-5).
(Chloromethanetriyl)tribenzene (cas: 76-83-5) belongs to organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. Organochlorine compounds are lipophylic, meaning they are more soluble in fat than in water. This gives them a high tenancy to accumulate in the food chain (biomagnification).Recommanded Product: 76-83-5
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics