In Vivo Quantification of 5-HT Brain Receptors in KO Rats with I-R91150 Single-Photon Emission Computed Tomography

Abstract

Our goal was to identify suitable image quantification methods to image 5-hydroxytryptamine 2A (5-HT 2A ) receptors in vivo in Mdr1a knockout (KO) rats (i.e., P-glycoprotein KO) using 123 I-R91150 single-photon emission computed tomography (SPECT). The 123 I-R91150 binding parameters estimated with different reference tissue models (simplified reference tissue model [SRTM], Logan reference tissue model, and tissue ratio [TR] method) were compared to the estimates obtained with a comprehensive three-tissue/seven-parameter (3T/7k)-based model. The SRTM and Logan reference tissue model estimates of 5-HT 2A receptor (5-HT 2A R) nondisplaceable binding potential (BP ND ) correlated well with the absolute receptor density measured with the 3T/7k gold standard ( r > .89). Quantification of 5-HT 2A R using the Logan reference tissue model required at least 90 minutes of scanning, whereas the SRTM required at least 110 minutes. The TR method estimates were also highly correlated to the 5-HT 2A R density ( r > .91) and only required a single 20-minute scan between 100 and 120 minutes postinjection. However, a systematic overestimation of the BP ND values was observed. The Logan reference tissue method is more convenient than the SRTM for the quantification of 5-HT 2A R in Mdr1a KO rats using 123 I-R91150 SPECT. The TR method is an interesting and simple alternative, despite its bias, as it still provides a valid index of 5-HT 2A R density.