title: Gd-AAZTA-MADEC, an improved blood pool agent for DCE-MRI studies on mice on 1 T scanners.
abstract: A novel MRI blood-pool contrast agent (Gd-AAZTA-MADEC) has been compared with established blood pool agents for tumor contrast enhanced images and angiography. Synthesis, relaxometric properties, albumin binding affinity and pharmacokinetic profiles are reported. For in vivo studies, angiographic images and tumor contrast enhanced images were acquired on mice with benchtop 1T-MRI scanners and compared with MS-325, B22956/1 and B25716/1. The design of this contrast agent involved the elongation of the spacer between the targeting deoxycholic acid moiety and the Gd-AAZTA imaging reporting unit that drastically changed either the binding affinity to albumin (KA(HSA) = 8.3 × 10(5) M(-1)) and the hydration state of the Gd ion (q = 2) in comparison to the recently reported B25716/1. The very markedly high binding affinity towards mouse and human serum albumins resulted in peculiar pharmacokinetics and relaxometric properties. The NMRD profiles clearly indicated that maximum efficiency is attainable at magnetic field strength of 1 T. In vivo studies showed high enhancement of the vasculature and a prolonged accumulation inside tumor. The herein reported pre-clinical imaging studies show that a great benefit arises from the combination of a benchtop MRI scanner operating at 1 T and the albumin-binding Gd-AAZTA-MADEC complex, for pursuing enhanced angiography and improved characterization of tumor vascular microenvironment.
authors.affiliation: Istituto di Biostrutture e Bioimmagini (CNR) c/o Molecular Biotechnology Center, Via Nizza 52, 10126, Torino, Italy; Molecular Imaging Center, University of Torino, Via Nizza 52, 10126, Torino, Italy. Electronic address: dario.longo@unito.it.
authors.forename: Dario Livio
authors.initials: DL
authors.lastname: Longo
authors.affiliation: Molecular Imaging Center, University of Torino, Via Nizza 52, 10126, Torino, Italy; Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126, Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Arena
authors.affiliation: Molecular Imaging Center, University of Torino, Via Nizza 52, 10126, Torino, Italy; Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126, Torino, Italy; CAGE Chemicals Srl, Via Bovio 6, 28100, Novara, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Consolino
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale "A. Avogadro" Largo Donegani 2/3, 28100, Novara, Italy; CAGE Chemicals Srl, Via Bovio 6, 28100, Novara, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Minazzi
authors.affiliation: Molecular Imaging Center, University of Torino, Via Nizza 52, 10126, Torino, Italy; Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126, Torino, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Geninatti-Crich
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale "A. Avogadro" Largo Donegani 2/3, 28100, Novara, Italy; CAGE Chemicals Srl, Via Bovio 6, 28100, Novara, Italy.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Giovenzana
authors.affiliation: Istituto di Biostrutture e Bioimmagini (CNR) c/o Molecular Biotechnology Center, Via Nizza 52, 10126, Torino, Italy; Molecular Imaging Center, University of Torino, Via Nizza 52, 10126, Torino, Italy; Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126, Torino, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D000818:Animals; D002793:Cholic Acids / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D003287:Contrast Media / Q000737:chemistry*; D056831:Coordination Complexes / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D015637:Gated Blood-Pool Imaging; D006801:Humans; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging / Q000295:instrumentation*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000175:diagnosis; D011485:Protein Binding; D066244:Proton Magnetic Resonance Spectroscopy; D011522:Protons; D012709:Serum Albumin / Q000378:metabolism; D014018:Tissue Distribution; D014867:Water
chemical_list: D002793:Cholic Acids; D003287:Contrast Media; D056831:Coordination Complexes; C000610586:Gd-AAZTA-MADEC; D011522:Protons; D012709:Serum Albumin; D014867:Water
keywords: Angiography; Blood pool imaging; DCE-MRI; Gadolinium contrast agent; Human serum albumin; Magnetic resonance imaging (MRI)