In vivo quantification of blood‐brain transfer and binding of [¹²⁵I]HEAT, an α₁‐adrenoceptor antagonist

The uptake and binding constants of [¹²⁵I]iodo‐2‐[β‐(4‐hydroxyphenyl)‐ethyl‐amino‐methyl]tetralone ([¹²⁵I]HEAT) in rat brain were determined in vivo. The initial clearance of the radioligand from blood to brain, K₁, was calculated from the initial uptake of the radioligand; it averaged 0.21 ± 0.01 (SD) ml g⁻¹ min ⁻¹, consistent with an initial extraction of 25% (i.e., one‐quarter of the blood flow). The most strongly binding regions included the olfactory bulb, thalamic nuclei, medial geniculate body, and cerebral cortical layers. We identified saturable, specific binding in frontal cortex layers 1, 5a, and 5c (motor region), frontal cortex layers 3 + 4, ventral thalamic nuclei, medial geniculate body, striatum, cerebellum, and olfactory bulb. Addition of unlabeled ligand depressed binding in all regions to the same low level (partition coefficient) of 0.8 ml g⁻¹. Displacement of [¹²⁵I]HEAT binding by unlabeled HEAT yielded a global affinity constant (K_DV_d) of 34 ± 8 pmol g⁻¹ and receptor densities (B_max) that varied from 50 pmol g⁻¹ in cerebellar cortex and caudate nucleus to 200 pmol g⁻¹ in the region of highest specific binding, the medial geniculate body.