Investigating plasma volume expanders as novel macromolecular MRI‐CEST contrast agents for tumor contrast‐enhanced imaging

Purpose The aim of this study was to investigate two clinically approved plasma volume expanders (dextran 70 and voluven) as macromolecular MRI‐chemical exchange saturation transfer (CEST) contrast agents to assess tumor vascular properties. Methods CEST contrast efficiency of both molecules (6% w/v) was measured in vitro at various irradiation saturation powers (1‐6 μT for 5 s) and pH values (range, 5.5‐7.9) and the exchange rate of hydroxyl protons was calculated. In vivo studies in a murine adenocarcinoma model (n = 4 mice for each contrast agent) upon i.v. injection provided CEST‐derived perfusion tumor properties that were compared with those obtained with a gadolinium‐based blood‐pool agent (Gd‐AAZTA‐Madec). Results In vitro measurements showed a marked CEST contrast dependency to pH, with higher CEST contrast at lower pH values for both molecules. The measured prototropic exchange rates confirmed a base‐catalyzed exchange rate that was faster for dextran 70 in comparison to voluven. Both molecules showed a similar CEST contrast increase (ΔST% > 3%) in the tumor tissue up to 30 min postinjection, with heterogeneous accumulation. In tumors receiving both CEST and T1‐weighted agents, a voxel‐by‐voxel analysis indicated moderate spatial correlation of perfusion properties between voluven/dextran 70 and Gd‐AAZTA‐Madec, suggesting different distribution patterns according to their molecular size. Conclusions The obtained results showed that both voluven and dextran 70 can be exploited as MRI‐CEST contrast agents for evaluating tumor enhancement properties. Their increased accumulation in tumors and prolonged contrast enhancement promote their use as blood‐pool MRI‐CEST agents to examine tumor vascularization.