Potential utility of ¹¹C-FPEB as a PET ligand for imaging metabotropic glutamate receptor 5 (mGluR5) in human brain

Objectives Metabotropic glutamate receptor 5 (mGluR5), a receptor involved in multiple neuropsychiatric disorders, has been imaged by several PET ligands among which ¹⁸F-FPEB is superior for an ¹⁸F-labeled ligand (J Cereb Blood Flow Metab 33:532). ¹¹C-ABP688 has ~8.5 fold lower affinity to mGluR5 and 6-10 fold lower distribution volume (V_T; a measure of receptor density) in brain compared to ¹⁸F-FPEB (J Cereb Blood Flow Metab 31:2169), and ¹¹C- and ¹⁸F-SP203 might produce radiometabolites entering brain that cause time instability of V_T (SNMMI 2013 AM, No. 415; J Nucl Med 49:2042). In this study, we evaluated whether FPEB labeled with ¹¹C, could be as useful as ¹⁸F-FPEB for kinetic imaging of mGluR5 in human brain.

Methods Six healthy subjects underwent ¹¹C-FPEB brain PET scans for 2 h with arterial blood sampling for metabolite corrected input function. V_T was determined by compartmental modeling and tested for time stability. Parametric modeling was performed using Logan and Ichise’s bilinear analysis (MA1).

Results ¹¹C-FPEB showed high brain uptake of ~7 peak SUV. Regional brain time-activity curves fitted well by unconstrained two-tissue compartment model. V_T values (mL/cm³) were well identified (<1.1% SE), and were highest in temporal cortex (18) and lowest in cerebellum (7) compatible with known distribution of mGluR5 receptors. In addition, V_T was stable at 60 min scan time (<5% change to that of full 2 h length data) indicating brain radioactivity is mostly from parent radioligand. Parametric modeling generated images with low noise. Values of voxel-wise V_T were similar to compartmental V_T with slight underestimation by Logan analysis but not by MA1. ¹¹C-FPEB V_T values were 3-6 folds higher than ¹¹C-ABP688, but ~1.6 fold lower than ¹⁸F-FPEB. The cause of lower V_T compared to ¹⁸F-FPEB is uncertain but may be related to differences in PET camera and input function modeling between institutions.

Conclusions ¹¹C-FPEB has favorable attributes to an extent similar to ¹⁸F-FPEB for PET imaging of mGluR5 in human brain.

Research Support NIMH Intramural Research Program