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

Autor: Consolino L; Molecular Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy., Irrera P; Molecular Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.; University of Campania Luigi Vanvitelli, Caserta, Italy., Romdhane F; Molecular Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy., Anemone A; Molecular Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy., Longo DL; Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), Turin, Italy.
Jazyk: angličtina
Zdroj: Magnetic resonance in medicine [Magn Reson Med] 2021 Aug; Vol. 86 (2), pp. 995-1007. Date of Electronic Publication: 2021 Mar 25.
DOI: 10.1002/mrm.28778
Abstrakt: 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 T 1 -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.
(© 2021 International Society for Magnetic Resonance in Medicine.)
Databáze: MEDLINE