Abstract
1771
Objectives Sympathetic nerve system (SNS) activation is known to play critical roles in the initiation and progression of heart failure. Several C11 labeled catecholamine analogs are available as PET tracers. However, such a F18 labeled PET compound, with a longer half-life enables delivery from central cyclotron facilities, and may contribute to a broader clinical application. Recently, the F18 sympathetic nerve PET tracer LMI1195 was introduced. The aim is to initially characterize the novel tracer using a rat model.
Methods Wistar rats were used in all experiments. Tracer accumulation in the heart was studied with following pretreatments: 1) nonselective norepinephrine (NE) uptake blocker phenoxybenzamine (PXB) 50mg/kg IV (n=3), 2) neural NE uptake-1 blocker desipramine (DMI) 2mg/kg IV (n=3), or 3) control with saline IV (n=3). PET tracer LMI1195 was injected 10 minutes after the pretreatment, and all rats were euthanized 10 minutes after the tracer injection for tissue counting. Three rats were imaged by micro PET. Heart to blood tissue count ratio (H/B ratio) was obtained using a gamma counter. Previously published experiments with I123 MIBG and C11 HED were used as reference employing the same protocol.
Results LMI1195 PET imaging showed clear delineation of the left ventricular wall. PXB pretreatment reduced the LMI1195 cardiac uptake by 70.9% (H/B ratio: control 12.7+/-0.2, PXB 3.7+/-0.9) comparable with MIBG (83.1%) and HED (89.8%). DMI showed discrepant results with preserved cardiac tracer uptake in LMI1195 (H/B ratio: 18.7+/-1.3) similarly to MIBG, while HED showed a reduced cardiac uptake with same protocol.
Conclusions LMI11195 cardiac uptake was specifically blocked with PXB indicating a promising property of the new class of PET tracer for imaging NE handling in rat hearts. High fraction of non-neural NE uptake in rodent hearts might be the reason for the discrepant results with DMI pretreatment