Kinetic analysis, biodistribution and radiation dosimetry of [¹¹C]IGA-1, a new PET radioligand to image translocator protein in nonhuman primates

Objectives The 18kDa translocator protein, TSPO is a biomarker for neuroinflammation. We developed a new PET radioligand for TSPO, [methyl-¹¹C]IGA-1, N,N-di-n-propyl-1-methyl-2-(4-nitrophenyl)indol-3-ylglyoxylamide and evaluated this radioligand in monkeys for its kinetics of brain uptake, biodistribution and estimated radiation absorbed doses for humans.

Methods Four rhesus monkeys had both a baseline and pre-block whole-body PET scan, two with PK11195 (PK; 5 mg/kg) and two with DCPQ (8 mg/kg) as blocking agent, and another a baseline brain scan, each after i.v. injection of [¹¹C]IGA-1 (211 ± 43 MBq) and with arterial blood sampling for 90 to 120 min. Regions of interest were drawn on brain and peripheral organs to determine the distribution volume V_T by compartmental analyses and to estimate the radiation absorbed doses by the MIRD method.

Results After injection of [¹¹C]IGA-1, baseline uptake of brain radioactivity was high (SUV ∼2) followed by slow washout. TSPO pre-block by PK increased peak radioactivity uptakes in plasma and brain (∼8 and 2-fold respectively) at ∼1 min, and decreased the brain and peripheral organ uptakes to a low common level at later time points. All brain time-activity curves fitted well with one-tissue compartment model (1-TCM) except for one PK pre-block, that fitted well with 2-TCM. Baseline brain V_T was ∼12−15 mL/cm³,which is ∼3-5-fold higher than that reported for [¹¹C]-(R)-PK. Majority of radioactivity (70-90%) was specific binding in brain and TSPO-expressing peripheral organs. P-glycoprotein pre-block by DCPQ minimally increased (∼30%) radioactivity in brain. Spleen had highest radiation exposure and the effective dose was 7.9 μSv/MBq.

Conclusions [¹¹C]IGA-1 is a promising ligand to quantify and localize inflammation with increased densities of TSPO