Mapping of carbonic anhydrase and estrone sulfatase in rat brain using 16-Alpha-[18F]Fluoroestradiol-3,17-Beta-disulphamate ([18F]FESDS)


Mapping of carbonic anhydrase and estrone sulfatase in rat brain using 16-Alpha-[18F]Fluoroestradiol-3,17-Beta-disulphamate ([18F]FESDS)

Rodig, H.; Brust, P.; Römer, J.; Kasch, H.; Bergmann, R.; Füchtner, F.; Steinbach, J.; Johannsen, B.

16-Alpha-[18F]Fluoroestradiol-3,17-Beta-disulphamate ([18F]FESDS) has recently been discovered to display affinity to carbonic anhydrase (CA) and estrone sulfatase (ES), enzymes which are expressed in the CNS and suggested to play a regulatory role in various brain diseases. In this study the radioligand was used to provide quantitative data on the regional distribution of these enzymes in the rat brain. The expression of CA I, CA II and ES has been studied in rat brain regions with RT-PCR. CA II and ES but not CA I has been detected in all regions. About 80-90 % of the total binding of [18F]FESDS to brain slices represents binding to CA (displaceable with acetazolamide). Binding of [18F]FESDS to ES was studied with selective inhibition of CA using acetazolamide. Bmax values of between 0.3 pmol/mg (pons) and 11.5 pmol/mg (striatum) were obtained in various brain regions. The Kd and Bmax values of ES binding were used as constants to calculate Kd and Bmax of CA binding from inhibition studies with FESDS. Bmax values of between 6.2 pmol/mg protein (striatum) and 14.6 pmol/mg (cerebellum) were obtained. The Kd-values varied between 33 nM and 166 nM, which is similar to the Kd of [18F]FESDS binding to purified human CA-II (54 nM). The affinity of FESDS to ES is lower by about factor 5. Furthermore, the enzymatic activity of ES in six rat brain regions was determined and found to be correlated to the corresponding [18F]FESDS binding. It is concluded, that [18F]FESDS can be used for mapping of CA and ES in vitro. The in vivo use of the radioligand may be limited because of its bipolar binding profile.

  • Poster
    International Brain '01, Taipei/Taiwan, 9.6.-13.6. 2001
  • Abstract in refereed journal
    J. Cereb. Blood Flow Metab. 21(Suppl.1) (2001) S552

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Publ.-Id: 3989