title: Design and synthesis of calcium responsive magnetic resonance imaging agent: Its relaxation and luminescence studies.
abstract: Calcium concentration modulation both inside and outside cell is of considerable interest for nervous system function in normal and pathological conditions. MRI has potential for very high spatial resolution at molecular/cellular level. Design, synthesis and evaluation of Gd-DO3A-AME-NPHE, a calcium responsive MRI contrast agent is presented. The probe is comprised of a Gd(3+)-DO3A core coupled to iminoacetate coordinating groups for calcium induced relaxivity switching. In the absence of Ca(2+) ions, inner sphere water binding to the Gd-DO3A-AME-NPHE is restricted with longitudinal relaxivity, r1 = 4.37 mM(-1) s(-1) at 4.7 T. However, addition of Ca(2+) triggers a marked enhancement in r1 = 6.99 mM(-1) s(-1) at 4.7 T (60% increase). The construct is highly selective for Ca(2+) over competitive metal ions at extracellular concentration. The r1 is modulated by changes in the hydration number (0.2 to 1.05), which was confirmed by luminescence emission lifetimes of the analogous Eu(3+) complex. T1 phantom images establish the capability of complex of visualizing changes in [Ca(2+)] by MRI.
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, Brig S. K. Mazumdar Road, Delhi 110054, India; Department of Chemistry, University of Delhi, Delhi 110054, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Tanwar
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, Brig S. K. Mazumdar Road, Delhi 110054, India. Electronic address: anupama@inmas.drdo.in.
authors.forename: Anupama
authors.initials: A
authors.lastname: Datta
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, Brig S. K. Mazumdar Road, Delhi 110054, India.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Chauhan
authors.affiliation: Department of N.M.R. and MRI, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: S Senthil
authors.initials: SS
authors.lastname: Kumaran
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, Brig S. K. Mazumdar Road, Delhi 110054, India.
authors.forename: Anjani K
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, Brig S. K. Mazumdar Road, Delhi 110054, India; Department of Chemistry, University of Delhi, Delhi 110054, India.
authors.forename: K Ganesh
authors.initials: KG
authors.lastname: Kadiyala
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, Brig S. K. Mazumdar Road, Delhi 110054, India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Pal
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110054, India.
authors.forename: M
authors.initials: M
authors.lastname: Thirumal
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, Brig S. K. Mazumdar Road, Delhi 110054, India. Electronic address: akmishra@inmas.drdo.in.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
mesh_terms: D002118:Calcium / Q000737:chemistry*; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D015195:Drug Design; D005682:Gadolinium / Q000737:chemistry*; D049449:Luminescence; D008163:Luminescent Measurements; D008279:Magnetic Resonance Imaging; D015394:Molecular Structure
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D005682:Gadolinium; D002118:Calcium
keywords: 1,4,7,10-Tetraaacyclododecane-1,4,7-tris(methylenecarboxylic acid); Calcium sensing; Gadolinium; Magnetic resonance imaging