Mathis CA, Holt DP, Huang GF, Lopresti BL, Debnath ML, Shao L, Klunk WE.
Species-dependent metabolism of [C-11]PiB.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Objectives: Recent studies have found that estrogen sulfotranferase metabolizes [C-11]PiB in rat brain (Cole et
al. PNAS 2010; 107: 6222). We sought to determine if this occurs to a significant degree in human brain tissue.
Methods: The radiolabeled metabolite of [C-11]PiB found in rat brain was identified and injected i.v. in mice, rats,
and baboons to determine brain uptake. Incubations of [H-3]PiB with mouse, rat, and human brain homogenates
were conducted to assess the production of the radiolabeled metabolite in brain tissues.
Results: Spectroscopic and chromatographic properties of chemically synthesized 6-sulfato-PiB were identical
to those of the metabolite extracted from rat liver and rat brain. Uptake studies indicated that [C-11]6-sulfato-
PiB did not enter mice, rat, or baboon brain to a significant extent following i.v. injection (brain concentrations
Conclusions: The radiolabeled metabolite of PiB found in rat brain is 6-sulfato-PiB. The metabolite is produced
peripherally in mice, rats, baboons, and humans, but does not cross the blood-brain barrier to a significant extent.
6-Sulfato-PiB is produced in rat brain, but is not produced to a significant degree in mouse or human brain tissues.
As in mice, radioactivity in the brain of human subjects following the i.v. injection of [C-11]PiB is likely comprised
of unmetabolized [C-11]PiB.