PET imaging of lung inflammation using [Ga-68]PRGD2 in a sickle cell disease model

1129 Objectives Our overall objective is to develop a diagnostic strategy for the identification of sickle cell disease (SCD) patients in imminent danger of developing acute chest syndrome (ACS), an acute lung injury syndrome responsible for the high mortality associated with SCD. An antecedent clinical event to ACS may be vaso-occlusive pain crisis, which is mediated by the hyperadhesion of blood cells to inflamed endothelium. The integrin αVβ3 is expressed on activated endothelium and may play a role in ACS. We hypothesized that PET/CT imaging using [Ga-68]PRGD2, a ligand for αVβ3 integrin, may assess pulmonary endothelial activation as an indicator of ACS risk in a mouse model of SCD. Methods Acute lung injury was induced in humanized transgenic mouse models of SCD (BERK SCD and BERK non-sickle control mice) and in wild type (C57BL/6L) mice by the intratracheal administration of bacterial endotoxin lipopolysaccharide (LPS; 1-5 mg/kg). Control groups received intratracheal saline. The radiotracer was synthesized by labeling PRGD2 (an RGD dimer linked to a chelator) with Ga-68, and injected via the tail vein 60 min. prior to PET/CT acquisition (7 MBq). Static 20 min. PET images were collected before and 2 h after LPS administration. Co-registration and volume of interest (VOI) analyses of the lungs were performed to obtain average SUVs as a measure of tracer uptake. Lungs were harvested and scored using histology to substantiate the development of ACS. Results WT mice showed a 1.8-fold increase in [Ga-68]PRGD2 lung uptake at 2 h post-LPS compared to baseline. In contrast, BERK SCD mice showed a 6.2-fold increase 2 h post-LPS relative to baseline. In addition, higher kidney uptake of tracer was observed compared to WT mice. Studies to investigate [Ga-68]PRGD2 uptake in lungs of WT and SCD mice at longer time-points post-LPS are underway. Conclusions Our results suggest that αVβ3 integrin is a reliable PET biomarker for inflammation due to activated endothelium in the SCD lung, a phenomenon linked to VOC. Human use approval to study whether [Ga-68]PRGD2 PET uptake predicts impending ACS in SCD patients hospitalized with VOC is in progress.