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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 (K A (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. [ABSTRACT FROM AUTHOR]

Abstract: Nanoparticles that circulate in the bloodstream for a prolonged period of time have important biomedicine applications. However, no example of lanthanide-based nanoparticles having a long-term circulation bloodstream has been reported to date. Herein, we report on difunctional radioactive and upconversion nanoparticles (UCNP) coated with polyphosphoric acid ligand, that is ethylenediamine tetramethylenephosphonic acid (EDTMP), for an application in single-photon emission computed tomography (SPECT) blood pool imaging. The structure, size and zeta-potential of the EDTMP-coated nanoparticles (EDTMP-UCNP) are verified using transmission electron microscopy and dynamic light scattering. Injection of radioisotope samarium-153-labeled EDTMP-UCNP (EDTMP-UCNP:153Sm) into mice reveal superior circulation time compared to control nanoparticles coated with citric acid (cit-UCNP:153Sm) and 153Sm complex of EDTMP (EDTMP-153Sm). The mechanism for the extended circulation time may be attributed to the adhesion of EDTMP-UCNP on the membrane of red blood cells (RBCs). In vivo toxicity results show no toxicity of EDTMP-UCNP at the dose of 100 mg/kg, validating its safety as an agent for blood pool imaging. Our results provide a new strategy of nanoprobe for a long-term circulation bloodstream by introducing polyphosphoric acid as surface ligand. [Copyright &y& Elsevier]

Abstract: Although polymeric magnetic resonance imaging (MRI) agents have significantly improved relaxivity and prolonged circulation time in vivo compared with current imaging agents, the potential for long-term toxicity prevents their translation into the clinic. The aim of this study was to develop a new biodegradable, nonionic polymeric blood pool MRI contrast agent with efficient clearance from the body. We synthesized PHPG-DTPA, which possesses two potentially degradable sites in vivo: protein amide bonds of the polymer backbone susceptible to enzymatic degradation and hydrolytically labile ester bonds in the side chains. After chelation with Gd3+, PHPG-DTPA-Gd displayed an R1 relaxivity of 15.72 mm −1⋅sec−1 (3.7 times higher than that of MagnevistT). In vitro, DTPA was completely released from PHPG polymer within 48 h when incubated in mouse plasma. In vivo, PHPG-DTPA-Gd was cleared via renal route as shown by micro-single photon emission computed tomography of mice after intravenous injection of 111In-labeled PHPG-DTPA-Gd. MRI of nude rats bearing C6 glioblastoma showed significant enhancement of the tumor periphery after intravenous injection of PHPG-DTPA-Gd. Furthermore, mouse brain angiography was clearly delineated up to 2 h after injection of PHPG-DTPA-Gd. PHPG-DTPA-Gd’s biodegradability, efficient clearance, and significantly increased relaxivity make it a promising polymeric blood pool MRI contrast agent. [Copyright &y& Elsevier]