Evaluation of [In]-Labeled Zinc-Dipicolylamine Tracers for SPECT Imaging of Bacterial Infection
Department of Radiology, Division of Nuclear Medicine
Bacterial Infections and Mycoses | Diagnosis | Medical Molecular Biology | Radiology
PURPOSE: This study prepared three structurally related zinc-dipicolylamine (ZnDPA) tracers with [111In] labels and conducted biodistribution and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging studies of a mouse leg infection model.
PROCEDURES: Two monovalent tracers, ZnDPA-[111In]DTPA and ZnDPA-[111In]DOTA, each with a single zinc-dipicolylamine targeting unit, and a divalent tracer, Bis(ZnDPA)-[111In]DTPA, with two zinc-dipicolylamine units were prepared. Organ biodistribution and SPECT and CT imaging studies were performed on living mice with a leg infection created by injection of clinically relevant Gram positive Streptococcus pyogenes. Fluorescent and luminescent Eu3+-labeled versions of these tracers were also prepared and used to measure relative affinity for the exterior membrane surface of bacterial cells and mimics of healthy mammalian cells.
RESULTS: All three 111In-labeled radiotracers were prepared with a radiopurity of greater than 90%. The biodistribution studies showed that the two monovalent tracers were cleared from the body through the liver and kidney, with retained percentage injected dose for all organs of < 8% at 20h and infected leg target to non-target ratio (T/NT) ratio of greater than or equal to 3.0. Clearance of the divalent tracer from the bloodstream was slower and primarily through the liver, with a retained percentage injected dose for all organs greater than 37% at 20h and T/NT ratio rising to 6.2 after 20 h. The SPECT/CT imaging indicated the same large difference in tracer pharmacokinetics and higher accumulation of the divalent tracer at the site of infection.
CONCLUSIONS: All three [111In]-ZnDPA tracers selectively targeted the site of a clinically relevant mouse infection model that could not be discerned by visual external inspection of the living animal. The highest target selectivity, observed with a divalent tracer equipped with two zinc-dipicolylamine targeting units, compares quite favorably with the imaging selectivities previously reported for other nuclear tracers that target bacterial cell surfaces. The tracer pharmacokinetics depended heavily on tracer molecular structure suggesting that it may be possible to rapidly fine tune the structural properties for optimized in vivo imaging performance and clinical translation.
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Citation: Mol Imaging Biol. 2014 Aug 13. doi:10.1007/s11307-014-0758-8. Link to article on publisher's site
Zinc–dipicolylamine, Infection imaging, SPECT/CT, 111-indium, Molecular tracer
Rice, Douglas R.; Plaunt, Adam J.; Turkyilmaz, Serhan; Smith, Miles; Wang, Yuzhen; Rusckowski, Mary; and Smith, Bradley D., "Evaluation of [In]-Labeled Zinc-Dipicolylamine Tracers for SPECT Imaging of Bacterial Infection" (2014). Radiology Publications and Presentations. 111.