WE‐H‐207A‐08: Characterization of a Broad‐Spectrum Cancer Targeted MRI Contrast Agent

Abstract

Purpose:To characterize the relaxation properties and tumor targeting capabilities of a novel alkylphosphocholine (APC) analog MR contrast agent, Gd‐DO3A‐404.Methods:Relaxivities were measured via T1 and T2 mapping of Gd‐DO3A‐404 with inversion recovery and spin echo pulse sequences, respectively. Uptake was characterized in flank xenograft models of non‐small cell lung cancer (A549) and glioma (U87) and compared with uptake of Dotarem. Mice (N=3 per model per agent) were delivered 2.34 moles contrast intravenously. T1‐weighted MRI and T1 maps were acquired pre‐contrast and at multiple time points up to seven days post‐contrast. For Dotarem imaging, T1‐weighted MRI was performed at multiple time points from one minute to one day.Results:Relaxivities of Gd‐DO3A‐404 in plasma were r1=5.74 and r2=20.4 s‐1/mm at 4.7T, comparing favorably to clinical contrast agent Dotarem (r1=3.3, r2=4.7). Specific, sustained uptake of Gd‐DO3A‐404 was observed in U87 and A549. The ratio of tumor:muscle T1‐weighted signal increased from 1.24 pre‐contrast to 2.12 twenty‐four hours post‐contrast in U87 and from 1.14 to 2.16 (same time points) in A549. Significant signal enhancement was maintained until 7 and 4 days post‐contrast in U87 and A549, respectively. In comparison, uptake and washout of Dotarem in U87 occurred over the course of fifteen minutes. The ratio of tumor:muscle T1‐weighted signal increased only 59% as much as Gd‐DO3A‐404, ranging from 1.15 pre‐contrast to a maximum of 1.67 five minutes post‐contrast. Significant signal enhancement from Dotarem was not sustained beyond one hour post‐contrast.Conclusion:These results indicate that with favorable relaxation characteristics and sustained signal‐enhancing uptake in multiple tumor models, Gd‐DO3A‐404 has great potential as a tumor‐targeting MR contrast agent. As part of a library of APC analogs labeled with PET/optical tracers and therapeutic radionuclides, Gd‐DO3A‐404 further expands theranostic capabilities. Future work will investigate applications in orthotopic glioma imaging, simultaneous PET/MR, and neutron capture therapy.