RT Journal Article
SR Electronic
T1 In Vivo Measurement of D<sub>2</sub> Receptor Density and Affinity for <sup>18</sup>F-(3-<em>N</em>-Methyl)Benperidol in the Rat Striatum with a PET System for Small Laboratory Animals
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 618
OP 624
VO 44
IS 4
A1 Susanne Nikolaus
A1 Rolf Larisch
A1 Markus Beu
A1 Karl Hamacher
A1 Farhad Forutan
A1 Henning Vosberg
A1 Hans-Wilhelm Müller
YR 2003
UL http://jnm.snmjournals.org/content/44/4/618.abstract
AB A recent investigation showed that intracerebral radioactivity concentrations can reliably be quantified in vivo with a small-animal PET device. The purpose of the current study was to investigate the binding characteristics of the D2 receptor radioligand 18F-(3-N-methyl)benperidol (18FMB) in rat striatum by determining receptor density (Bmax) and affinity (Kd) in vivo. For validation, Kd and Bmax additionally were determined in vitro using storage phosphor autoradiography. Methods: Striatal radioactivity was measured with PET in 8 Sprague-Dawley rats after injection of 18FMB in increasing specific activities. Free radioligand concentrations were estimated from cortical radioactivity concentrations and were subtracted from striatal radioactivity concentrations to obtain specific binding. In vitro saturation experiments were performed on 7 further rats according to the isotopic dilution method. Specific binding was determined by both subtraction of 18FMB binding in the presence of raclopride and subtraction of cortical radioactivity concentrations from total radioligand binding. Saturation binding curves were obtained by plotting specifically bound radioligand concentrations against free radioligand concentrations and were evaluated with regression analysis. Results: PET yielded a Kd of 6.2 nmol/L and a Bmax of 16 fmol/mg for the striatal D2 receptor. In vitro, Kd and Bmax amounted to 4.4 nmol/L and 84.1 fmol/mg (subtraction of 18FMB binding in the presence of raclopride), respectively, and 7.9 nmol/L and 70.1 fmol/mg (subtraction of cortical radioactivity concentrations), respectively. Conclusion: Kd values measured with PET and autoradiography agreed and corresponded to inhibition constants obtained in previous in vitro studies. Bmax values lay within the same order of magnitude. The results of in vitro saturation binding analyses also agreed, irrespective of the mode of determination of free radioligand concentrations. Thus, Bmax and Kd may be determined with PET in analogy to the evaluation of in vitro binding data by regression analysis of bound-versus-free ligand concentrations. Our results show that small-animal tomographs are valuable tools for the in vivo characterization of receptor radioligands as an alternative to autoradiography.