title: Optimized time-resolved imaging of contrast kinetics (TRICKS) in dynamic contrast-enhanced MRI after peptide receptor radionuclide therapy in small animal tumor models.
abstract: Anti-tumor efficacy of targeted peptide-receptor radionuclide therapy (PRRT) relies on several factors, including functional tumor vasculature. Little is known about the effect of PRRT on tumor vasculature. With dynamic contrast-enhanced (DCE-) MRI, functional vasculature is imaged and quantified using contrast agents. In small animals DCE-MRI is a challenging application. We optimized a clinical sequence for fast hemodynamic acquisitions, time-resolved imaging of contrast kinetics (TRICKS), to obtain DCE-MRI images at both high spatial and high temporal resolution in mice and rats. Using TRICKS, functional vasculature was measured prior to PRRT and longitudinally to investigate the effect of treatment on tumor vascular characteristics. Nude mice bearing H69 tumor xenografts and rats bearing syngeneic CA20948 tumors were used to study perfusion following PRRT administration with (177) lutetium octreotate. Both semi-quantitative and quantitative parameters were calculated. Treatment efficacy was measured by tumor-size reduction. Optimized TRICKS enabled MRI at 0.032 mm(3) voxel size with a temporal resolution of less than 5 s and large volume coverage, a substantial improvement over routine pre-clinical DCE-MRI studies. Tumor response to therapy was reflected in changes in tumor perfusion/permeability parameters. The H69 tumor model showed pronounced changes in DCE-derived parameters following PRRT. The rat CA20948 tumor model showed more heterogeneity in both treatment outcome and perfusion parameters. TRICKS enabled the acquisition of DCE-MRI at both high temporal resolution (Tres ) and spatial resolutions relevant for small animal tumor models. With the high Tres enabled by TRICKS, accurate pharmacokinetic data modeling was feasible. DCE-MRI parameters revealed changes over time and showed a clear relationship between tumor size and Ktrans .
authors.affiliation: Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands.|Department of Medical Informatics, Erasmus Medical Centre, Rotterdam, The Netherlands.|Department of Nuclear Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Haeck
authors.affiliation: Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands.|Department of Medical Informatics, Erasmus Medical Centre, Rotterdam, The Netherlands.|Department of Nuclear Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Bol
authors.affiliation: Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands.|Department of Medical Informatics, Erasmus Medical Centre, Rotterdam, The Netherlands.|Department of Nuclear Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Bison
authors.affiliation: Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: van Tiel
authors.affiliation: Department of Nuclear Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Stuart
authors.initials: S
authors.lastname: Koelewijn
authors.affiliation: Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands.|Department of Nuclear Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Marion
authors.initials: M
authors.lastname: de Jong
authors.affiliation: Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands.|Department of Medical Informatics, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Jifke
authors.initials: J
authors.lastname: Veenland
authors.affiliation: Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands.|Department of Nuclear Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Bernsen
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008187:Lutetium / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000532:radiotherapy; D010477:Perfusion / Q000379:methods; D011859:Radiography; D011868:Radioisotopes / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D018000:Receptors, Peptide / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D011868:Radioisotopes; D018000:Receptors, Peptide; D008187:Lutetium
keywords: DCE-MRI; PRRT; TRICKS; small animal imaging; tumor