5-HT2A receptor SPECT imaging with [¹²³I]R91150 under P-gp inhibition with tariquidar: More is better?

Nucl Med Biol. 2016 Jan;43(1):81-88. doi: 10.1016/j.nucmedbio.2015.09.003. Epub 2015 Sep 11.


Introduction: Pharmacological P-glycoprotein (P-gp) inhibition with tariquidar (TQD) is considered a promising strategy for the augmentation of radiotracer brain uptake. However, a region-dependent effect may compromise the robustness of quantitative studies. For this reason, we studied the effect of a TQD pretreatment on 5-HT2A imaging with [(123)I]R91150 and compared results with those obtained in Mdr1a knock-out (KO) rats.

Methods: Ex vivo autoradiography was performed in TQD (15 mg/kg) pretreated wild-type (WT-TQD), Mdr1a knock-out (KO) and untreated WT rats for Specific Binding Ratio (SBR) estimation. In vivo dynamic SPECT imaging with serial arterial blood sampling was performed in the former two groups of rats and kinetic analysis was performed with a one tissue-compartment (1TC) model and the Specific Uptake Ratio (SUR). Results were analyzed statistically using repeated measures ANOVA.

Results: SBR values differed between WT-TQD, Mdr1a KO and WT rats in a region-dependent manner (p<0.0001). In vivo brain uptake of radiotracer did not differ between groups. Similarly, kinetic analysis provided distribution volume (V(T)) values that did not differ significantly between groups. SUR binding potential (BPND) values from both groups highly correlated with corresponding V(T) (r=0.970, p<0.0001 and r=0.962, p<0.0001, respectively). However, SUR measured over averaged images between 100 and 120 min, using cerebellum as reference region, demonstrated values that were, by average, 2.99±0.53 times higher in the WT-TQD group, with the difference between groups being region-dependent (p<0.001). In addition, coefficient of variation of the SUR BPND values across brain regions was significantly higher in the WT-TQD rats (41.25%±9.63% versus 11.13%±5.59%, p<0.0001).

Conclusion: P-gp inhibition with TQD leads to region-dependent effect in the rat brain, with probably sub-optimal effect in cerebellum. This warrants attention when it is used as a reference region for quantitative studies.

Keywords: 5-HT2A receptors; Multi-drug resistance protein; P-glycoprotein; R91150; SPECT; Tariquidar.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / deficiency
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Animals
  • Gene Knockout Techniques
  • Iodine Radioisotopes*
  • Male
  • Piperidines*
  • Quinolines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Tomography, Emission-Computed, Single-Photon / methods*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Iodine Radioisotopes
  • Piperidines
  • Quinolines
  • R 91150
  • Receptor, Serotonin, 5-HT2A
  • tariquidar