preclinical evaluation of carbon-11 and fluorine-18 sulfonamide derivatives for in vivo radiolabeling of erythrocytes临床前评价carbon-11和氟18磺酰胺衍生品体内放射性标记的红细胞.pdf

Gheysens et al. EJNMMI Research 2013, 3:4 /content/3/1/4 ORIGINAL RESEARCH Open Access Preclinical evaluation of carbon-11 and fluorine- 18 sulfonamide derivatives for in vivo radiolabeling of erythrocytes 1,2† 3† 3 4 3 1,2 Olivier Gheysens , Vamsidhar Akurathi , Rufael Chekol , Tom Dresselaers , Sofie Celen , Michel Koole , 5,6 3 7 5,6 3 1,2 Dieter Dauwe , Bernard J Cleynhens , Piet Claus , Stefan Janssens , Alfons M Verbruggen , Johan Nuyts , Uwe Himmelreich4 and Guy M Bormans3* Abstract Background: To date, few PET tracers for in vivo labeling of red blood cells (RBCs) are available. In this study, we report the radiosynthesis and in vitro and in vivo evaluation of 11C and 18F sulfonamide derivatives targeting carbonic anhydrase II (CA II), a metallo-enzyme expressed in RBCs, as potential blood pool tracers. A proof-of-concept in vivo imaging study was performed to demonstrate the feasibility to assess cardiac function and volumes using electrocardiogram (ECG)-gated positron emission tomography (PET) acquisition in comparison with cine magnetic resonance imaging (cMRI) in rats and a pig model of myocardial infarction. Methods: The inhibition constants (Ki) of CA II were determined in vitro for the different compounds by assaying CA-catalyzed CO2 hydration activity. Binding to human RBCs was estimated after in vitro incubation of the compounds with whole blood. Biodistribution studies were performed to evaluate tracer kinetics in NMRI mice. ECG-gated PET acquisition was performed in Wistar rats at rest and during pharma