Validation of Di-5-HT-Gd-DTPA, an Enzyme-Specific MR Contrast Agent for Myeloperoxidase, in the Rabbit Elastase Model of Cerebrovascular Aneurysm

Characterization of molecular imaging probes in multiple animal models of disease is essential to increase their diagnostic potential. For example, we recently demonstrated visualization of active inflammation in a rabbit model saccular aneurysm using clinical field strength MRI and the paramagnetic MR contrast agent di-5-HT-GdDTPA, which has been shown in vitro to be sensitive and specific for the enzyme myeloperoxidase (MPO). While the use of transgenic mice (MPO^−/−) has demonstrated specificity of di-5-HT-GdDTPA for MPO in a model of myocardial infarction [1], MPO-deficient rabbits are not available. Therefore, in this study, we sought to validate di-5-HT-GdDTPA MPO specificity in the New Zealand white rabbit by comparing serial enhancement ratios of di-5-HT-GdDTPA to a structurally similar MR contrast agent, di-Tyr-GdDTPA, which is activated by peroxidases but not by MPO. Structural diagrams of the synthesis of the two agents are demonstrated in Figure 1 [2].