LMI1195 PET neuronal imaging: Evaluation of cardiac denervation, re-innervation and associated susceptibility to arrhythmia

Objectives Regional cardiac sympathetic denervation (RCSD) has been associated with cardiac arrhythmia in heart failure patients. LMI1195 is a newly developed 18F labeled cardiac neuronal imaging agent which takes advantages of the high spatial resolution and quantification offered by PET. This study evaluated if LMI1195 cardiac imaging could be used to measure RCSD, subsequent re-innervation and potential RCSD association with arrhythmia susceptibility.

Methods RCSD rabbits were developed by applying phenol directly on the surface of the left ventricular wall during a sternotomy. Two and twelve weeks following the procedure, LMI1195 cardiac imaging (1.5 mCi, iv) was performed. The myocardium with radioactivity ≥ 50% maximum was quantified as an innervated region for comparison. To evaluate the susceptibility to arrhythmia in these rabbits, cardiac changes induced by dofetilide (a delayed IKr inhibitor, 10 and 40 µg/kg iv) were assessed by measuring ECG including heart rate (HR), QTc interval (corrected by Fridericia method) and frequency of arrhythmia.

Results Cardiac imaging showed homogeneous myocardial uptake of LMI1195 in sham-denervated rabbits and reduced regional levels in RCSD rabbits at 2 weeks post surgery (innervated region: 21276±3100 vs. 12970±1108 voxels respectively). The denervated region was reduced at 12 weeks (innervated region: 16812±503 voxels) indicating re-innervation. Imaging with flurpiridaz F 18 (a PET perfusion imaging agent) in these rabbits showed normal myocardial distribution without perfusion interruption after the RCSD procedure. Dofetilide induced QTc prolongation, frequency of premature ventricular contraction and torsade de pointes were more prominent in the RCSD group than in the control. However, the changes in HR were comparable in the two groups.

Conclusions LMI1195 cardiac imaging can be use in detection of RCSD and re-innervation. The RCSD increases susceptibility of drug induced QTc prolongation and arrhythmia