Lumazine Synthase Protein Nanoparticle-Gd(III)-DOTA Conjugate as a T1 contrast agent for high-field MRI.
With the applications of magnetic resonance imaging (MRI) at higher magnetic fields increasing, there is demand for MRI contrast agents with improved relaxivity at higher magnetic fields. Macromolecule-based contrast agents, such as protein-based ones, are known to yield significantly higher r1 relaxivity at low fields, but tend to lose this merit when used as T1 contrast agents (r1/r2 = 0.5 ~ 1), with their r1 decreasing and r2 increasing as magnetic field strength increases. Here, we developed and characterized an in vivo applicable magnetic resonance (MR) positive contrast agent by conjugating Gd(III)-chelating agent complexes to lumazine synthase isolated from Aquifex aeolicus (AaLS). The r1 relaxivity of Gd(III)-DOTA-AaLS-R108C was 16.49 mM(-1)s(-1) and its r1/r2 ratio was 0.52 at the magnetic field strength of 7 T. The results of 3D MR angiography demonstrated the feasibility of vasculature imaging within 2 h of intravenous injection of the agent and a significant reduction in T1 values were observed in the tumor region 7 h post-injection in the SCC-7 flank tumor model. Our findings suggest that Gd(III)-DOTA-AaLS-R108C could serve as a potential theranostic nanoplatform at high magnetic field strength.
Department of Biomedical Engineering, School of Life Science, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea.
YoungKyu
Y
Song
Department of Biological Sciences, School of Life Science, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea.
Young Ji
YJ
Kang
Department of Biomedical Engineering, School of Life Science, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea.
Hoesu
H
Jung
Department of Biological Sciences, School of Life Science, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea.
Hansol
H
Kim
Department of Biological Sciences, School of Life Science, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea.
Sebyung
S
Kang
Department of Biomedical Engineering, School of Life Science, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea.
HyungJoon
H
Cho
D000818:Animals; D003287:Contrast Media; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000473:pathology; D009942:Organometallic Compounds / Q000737:chemistry*
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009097:Multienzyme Complexes; D009942:Organometallic Compounds; C044822:6,7-dimethyl-8-ribityllumazine synthase; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate