Fluoro analogs of WAY-100635 with varying pharmacokinetics properties

Lang, Lixin; Jagoda, Elaine M.; Schmall, Bernard; Sassaman, Mark B.; Ma, Ying; Eckelman, William C.

doi:10.1016/s0969-8051(00)00111-6

Cited by 35 publications

(19 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 18 F]FPWAY was produced as described (31). There were no differences in the specific activity across groups [males: 1521.2 ± 341.4, females: 2014.8 ± 331.9 (p>0.3); MR: 1454.5 ± 206.9, PR: 2081.5 ± 419.0 (p>0.2)].…”

Section: Methodsmentioning

confidence: 99%

Effects of Early-Life Stress on Serotonin1A Receptors in Juvenile Rhesus Monkeys Measured by Positron Emission Tomography

Spinelli

Chefer

Carson

et al. 2010

Biological Psychiatry

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 99%

Effects of Early-Life Stress on Serotonin1A Receptors in Juvenile Rhesus Monkeys Measured by Positron Emission Tomography

Spinelli

Chefer

Carson

et al. 2010

Biological Psychiatry

Self Cite

View full text Add to dashboard Cite

show abstract

“…18 F]Mefway can be radiolabeled as two different isomeric forms at the 4-cyclohexyl position, representing cis-[ 18 F]mefway and trans-[ 18 F]mefway, which are shown in Figure 1. The varying binding affinity of isomeric forms of another closely related PET radioligand, 4-[ 18 F]FCWAY, has been investigated [5]. The conformation of trans- and cis- [ 18 F]FCWAY displayed a dramatic difference in 5-HT 1A binding with reported IC 50 values of 1.7nM and 21nM, respectively.…”

Section: Introductionmentioning

confidence: 99%

An in vivo comparison of cis- and trans-[18F]mefway in the nonhuman primate

Hillmer

Murali

Barnhart

et al. 2011

Nuclear Medicine and Biology

View full text Add to dashboard Cite

Introduction [18F]Mefway is a serotonin 5-HT1A PET radiotracer with high specificity and favorable in vivo imaging properties. The chemical structure of 18F]mefway permits 18F labeling in either the cis- or trans- positions at the 4-cyclohexyl site. We have previously reported on the in vivo kinetics of trans-[18F]mefway in the nonhuman primate. In this work we compare in vivo binding of cis-[18F]mefway and trans-[18F]mefway to evaluate the properties of cis-[18F]mefway for 5-HT1A PET imaging. Methods The cis- and trans- [18F]mefway tracers were synthesized via nucleophilic substitution with their respective tosylate precursors. Two monkeys (1m, 1f) were given bolus injections of both cis- and trans- labeled [18F]mefway in separate experiments. Dynamic scans were acquired for 90 minutes with a microPET P4 scanner. Time activity curves were extracted in the areas of the mesial temporal cortex (MTC), anterior cingulate gyrus (aCG), insular cortex (IC), raphe nuclei (RN), and cerebellum (CB). The in vivo behavior of the radiotracers were compared based upon the nondisplaceable binding potential (BPND) using the CB as a reference region. Results Averaged over the 2 subjects, BPND values were MTC: 7.7, 0.58; aCG: 4.95, 0.32; IC: 3.27, 0.2; and RN: 3.05, 0.13 for trans-[18F]mefway and cis-[18F]mefway, respectively. Conclusion The cis- labeled [18F]mefway tracer has low specific binding throughout the 5-HT1A regions of brain compared to trans-[18F]mefway suggesting that the target to background binding of cis-[18F]mefway may limit its use for in vivo assessment of 5-HT1A binding.

show abstract

“…The pharmaceutical industry integrated LC/MS into its drug discovery process several years ago [8]. Identification of metabolites of radiopharmaceuticals, which is complicated by the short half-lives of the radionuclides and the very low dose of the compound [typically less than 10 nmol] administered, may provide suggestions as to the most appropriate position in the molecule to attach the radiolabel and allow the synthesis and study of the bio-distribution of the metabolite(s) [9, 10]. …”

Section: Metabolite Identificationmentioning

confidence: 99%

“…Placing the fluorine in the cyclohexane ring resulted in formation of different isomers. We examined the relationship between structure and metabolism [9, 10, 37, 38]. The first four compounds, prepared both chemically and radiochemically, were 4- cis , 4- trans , 3- cis , and 3- trans isomers of N -{2-[4-(2-metho-xyphenyl)piperazinyl]ethyl}- N -(pyridin-2-yl) -fluorocyclohexane-carboxamides (FCWAY’s) Fig.…”

Section: Metabolite Identificationmentioning

confidence: 99%

Applications of LC-MS in PET Radioligand Development and Metabolic Elucidation

Ma¹,

Kiesewetter²,

Lang³

et al. 2010

CDM

Self Cite

View full text Add to dashboard Cite

Positron emission tomography (PET) is a very sensitive molecular imaging technique that when employed with an appropriate radioligand has the ability to quantititate physiological processes in a non-invasive manner. Since the imaging technique detects all radioactive emissions in the field of view, the presence and biological activity of radiolabeled metabolites must be determined for each radioligand in order to validate the utility of the radiotracer for measuring the desired physiological process. Thus, the identification of metabolic profiles of radiolabeled compounds is an important aspect of design, development, and validation of new radiopharmaceuticals and their applications in drug development and molecular imaging. Metabolite identification for different chemical classes of radiopharmaceuticals allows rational design to minimize the formation and accumulation of metabolites in the target tissue, either through enhanced excretion or minimized metabolism. This review will discuss methods for identifying and quantitating metabolites during the pre-clinical development of radiopharmaceuticals with special emphasis on the application of LC/MS.

show abstract

Fluoro analogs of WAY-100635 with varying pharmacokinetics properties

Cited by 35 publications

References 18 publications

Effects of Early-Life Stress on Serotonin1A Receptors in Juvenile Rhesus Monkeys Measured by Positron Emission Tomography

Effects of Early-Life Stress on Serotonin1A Receptors in Juvenile Rhesus Monkeys Measured by Positron Emission Tomography

An in vivo comparison of cis- and trans-[18F]mefway in the nonhuman primate

Applications of LC-MS in PET Radioligand Development and Metabolic Elucidation

Contact Info

Product

Resources

About