11C-labelling of dimethylphenethylamine in two different positions and biodistribution studies

In Vivo Metabolic Trapping Radiotracers for Imaging Monoamine Oxidase-A and -B Enzymatic Activity

“…However, due to the well-known potential for species differences in the selectivity and rates of substrate oxidations by the monoamine oxidases 7a, 14 , additional studies were performed in the rhesus monkey.…”

“…The failure to achieve isozyme selectivity (or specificity) for any of the radiotracers in the rat brain was however not discouraging. The prior studies 11a, 12 of 1-methyl-4-aryloxy-1,2,3,6-tetrahydropyridines had utilized MAO isolated from bovine or human tissues (or both), and numerous studies have demonstrated significant species variability in the behavior of both inhibitors and substrates towards the two isozymes of MAO 7a, 14 . This variability supported the notion that our new radiotracers needed to be evaluated in a second species.…”

Considerations in the Development of Reversibly Binding PET Radioligands for Brain Imaging

“…A radioligand with a carbon-11 label in a secondary N -methyl-amino position may be metabolized similarly and therefore just as benignly. However, a radioligand with a carbon-11 label in a tertiary N , N -dimethylamino group has a risk of being cleaved by monoamine oxidase within the brain to release [ 11 C]dimethylamine, which then becomes protonated and unable to leave brain [233], or of being metabolized to the radioactive secondary methylamine, which may well enter brain and in some cases show some specific binding to the target or other proteins. A notable exception is the SERT radioligand, [ 11 C]MAD-AM, which performs acceptably well with the carbon-11 label in its dimethylamino position [234].…”

Pet Imaging Studies in Drug Abuse Research

“…. measurement of the input function became an integral part of the study and that rapid and sometimes automated methods for making these measures were developed (Alexoff et al, 1995 are, however, mechanistic tools which have been applied in humans, including stereoselective binding when the tracer or drug contains a chiral center (Fowier et al, 1987;Ding et al, 1997), pharmacological blockade when safety and toxicity permit (Fowler et al, 1996a) the use of deuterium isotope effects (when there is a labile C-H bond in a rate-limiting step) (Fowler et al, 1988 and labeling in different positions (Halldin et al, 1989;Gatley et al, 1994).…”

“…. measurement of the input function became an integral part of the study and that rapid and sometimes automated methods for making these measures were developed (Alexoff et al, 1995 are, however, mechanistic tools which have been applied in humans, including stereoselective binding when the tracer or drug contains a chiral center (Fowier et al, 1987;Ding et al, 1997), pharmacological blockade when safety and toxicity permit (Fowler et al, 1996a) the use of deuterium isotope effects (when there is a labile C-H bond in a rate-limiting step) (Fowler et al, 1988 and labeling in different positions (Halldin et al, 1989;Gatley et al, 1994).Additionally other neuroscience tools such as microdialysis have been combined with imaging to assess the relationship between changes in radiotracer concentration as measured by PET and neurotransmitter release (Breier et al, 1997;Dewey et al, 1999). In the near future, the development and use of small animal PET instruments promises to streamline the process and allow imaging of genetically modified animals (Chatziioannou et al, 1999;Jeavons et al,1999).…”