Myocardial imaging with Tc-99m EDA-ESM: Safety, biodistribution and dosimetry in animal models

Objectives Esmolol (ESM) binds to beta-1 receptors in heart tissue and reduces morbidity and mortality in patients with various cardiac diseases. Previously, we reported the cardiac uptake of Tc-99m ethylenediamine-esmolol (EDA-ESM) was via a receptor mediated process (Oh CS, JNM 2010; 51 (supp2):299). The optimal dosage for cardiac uptake of Tc-99m EDA-ESM was 0.2 mg/kg in rats at 30 min by planar imaging. This study was aimed to evaluate safety, biodistribution and dosimetry of Tc-99m EDA-ESM in normal rats.

Methods EDA-ESM is synthesized by reacting ESM with EDA followed by purification. For acute toxicity studies, F-344 rats were administered with EDA-ESM. Blood chemistries on day 0, 3 and 14 were measured. Biodistribution of Tc-99m EDA-ESM and ¹⁸F-FDG were performed in normal F-344 rats. Rat absorbed doses estimates for Tc-99m EDA-ESM were computed based on their respective biodistribution data. Residence times were then used to calculate target organ absorbed radiation doses for a standard 70 kg male model using the Olinda software package.

Results EDA-ESM dosages up to 1.0 mg/rat are well tolerated by rats. The imaging dose at 0.2 mg/kg in rats showed no acute toxicity. The imaging dose in rats per kg is 350 times more than dose proposed in human. In biodistribution, the cardiac uptake (%ID/g) at 30 min for Tc-99m EDA-ESM and ¹⁸F-FDG was 1.00±0.12 and 1.43±0.04, respectively. Tc-99m EDA-ESM had poor brain uptake whereas ¹⁸F-FDG had high brain uptake. Based upon preclinical studies, radiation exposure to the whole body, blood-forming organs, gonads and effective dose equivalent are far below the limits of the maximum allowed dose.

Conclusions Dosimetry data revealed that Tc-99m EDA-ESM is safe for imaging at the dose 0.2 mg/kg (iv) in rats. Tc-99m EDA-ESM SPECT could provide quantitative analysis of cardiac-adrenergic receptor sites for early detection of cardiac disorders