Abstract 570: Heart Failure Imaging in the Rat With LMI1195: A New PET Cardiac Neuronal Imaging Agent
LMI1195 is a new 18F-benzylguanidine analog being developed to assess cardiac neuronal function by targeting the norepinephrine transporter. The objective of this study was to evaluate the prognostic value of LMI1195 in Dahl Salt Sensitive (DSS) rats, a rat model of heart failure (HF), and compare with 123I-meta-iodobenzylguanidine (123I-MIBG). DSS rats were fed either a low salt (0.1% as control) or high salt diet (8%) for 5 or 9 weeks. To determine the progression of HF in these rats, plasma norepinephrine levels, and heart and lung weights were measured. Compared to low salt diet groups, DSS rats fed a high salt diet for 5 weeks had marked increases in norepinephrine levels (258±28 vs. 1242±184 pg/mL) and heart to body weight ratio (3.3±0.1 vs. 4.5±0.3 mg/g). By 9 weeks, the norepinephrine levels (656±219 vs. 1508±165 pg/mL) and heart to body weight ratio (3.2±0.1 vs. 6.1±0.3 mg/g) had increased further and the lung to body weight ratio had become elevated (3.9±0.1 vs. 14.0±1.4 mg/g). These rats fed a high salt diet were demonstrated to develop HF from early stage with myocardial hypertrophy (5-week) to late stage with sever lung congestion (9-week). LMI1195 and MIBG heart uptake was examined in early and late stage HF rats by tissue sampling after intravenous administration. The uptake was measured using a gamma counter and expressed as differential absorption ratio (DAR). The LMI1195 heart uptake decreased following progression of HF from early to late stage HF (low salt group vs. high salt group: 6.9±0.6 vs. 5.1±0.6 and 8.1±0.2 vs. 3.1±0.2 DAR at 5 and 9 weeks respectively). These findings were comparable with the heart uptake of 123I-MIBG in these rats (7.3±0.1 vs. 3.8±0.5 and 7.9±0.5 vs. 2.3±0.3 DAR respectively). Cardiac PET imaging with LMI1195 in DSS rats fed a low salt diet showed clear myocardium with minimal background interference from blood, lung and liver. Consistent with the findings in the tissue sampling, imaging in DSS rats fed a high salt diet showed progressively reduced radioactivity in the heart of these rats from 5 to 9 weeks. These results suggest that the profile of LMI1195 is similar to 123I-MIBG and cardiac imaging with LMI1195 can be used to detect progression of HF in DSS rats.