PT  - JOURNAL ARTICLE
AU  - Lohith, Talakad
AU  - Fujita, Masahiro
AU  - Kimura, Yasuyuki
AU  - Zoghbi, Sami
AU  - Hong, Jinsoo
AU  - Martini, Claudia
AU  - Taliani, Sabrina
AU  - Da Settimo, Federico
AU  - Pike, Victor
AU  - Innis, Robert
TI  - Kinetic analysis, biodistribution and radiation dosimetry of [<sup>11</sup>C]IGA-1, a new PET radioligand to image translocator protein in nonhuman primates
DP  - 2011 May 01
TA  - Journal of Nuclear Medicine
PG  - 396--396
VI  - 52
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/52/supplement_1/396.short
4100  - http://jnm.snmjournals.org/content/52/supplement_1/396.full
SO  - J Nucl Med2011 May 01; 52
AB  - 396 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 VT 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 VT 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