title: Characterisation and evaluation of paramagnetic fluorine labelled glycol chitosan conjugates for (19)F and (1)H magnetic resonance imaging.
abstract: Medium molecular weight glycol chitosan conjugates have been prepared, linked by an amide bond to paramagnetic Gd(III), Ho(III) and Dy(III) macrocyclic complexes in which a trifluoromethyl reporter group is located 6.5 Å from the paramagnetic centre. The faster relaxation of the observed nucleus allows modified pulse sequences to be used with shorter acquisition times. The polydisperse materials have been characterised by gel permeation chromatography, revealing an average molecular weight on the order of 13,800 (Gd), 14,600 (Dy) and 16,200 (Ho), consistent with the presence of 8.5, 9.5 and 13 complexes, respectively. The gadolinium conjugate was prepared for both a q = 1 monoamide tricarboxylate conjugate (r1p 11.2 mM(-1) s(-1), 310 K, 1.4 T) and a q = 0 triphosphinate system, and conventional contrast-enhanced proton MRI studies at 7 T were undertaken in mice bearing an HT-29 or an HCT-116 colorectal tumour xenograft (17 μmol/kg). Enhanced contrast was observed following injection in the tail vein in tumour tissue, with uptake also evident in the liver and kidney with a tumour-to-liver ratio of 2:1 at 13 min, and large amounts in the kidney and bladder consistent with predominant renal clearance. Parallel experiments observing the (19)F resonance in the holmium conjugate complex using a surface coil did not succeed owing to its high R2 value (750 Hz, 7 T). However, the fluorine signal in the dysprosium triphosphinate chitosan conjugate [R1/R2 = 0.6 and R1 = 145 Hz (7 T)] was sharper and could be observed in vivo at -65.7 ppm, following intravenous tail vein injection of a dose of 34 μmol/kg.
authors: Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
authors: Elena
authors: E
authors: De Luca
authors: Peter
authors: P
authors: Harvey
authors: Kirsten H
authors: KH
authors: Chalmers
authors: Anurag
authors: A
authors: Mishra
authors: P Kanthi
authors: PK
authors: Senanayake
authors: J Ian
authors: JI
authors: Wilson
authors: Mauro
authors: M
authors: Botta
authors: Marianna
authors: M
authors: Fekete
authors: Andrew M
authors: AM
authors: Blamire
authors: David
authors: D
authors: Parker
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D048271:Chitosan / Q000138:chemical synthesis* / Q000737:chemistry*; D005461:Fluorine; D019073:HT29 Cells; D006801:Humans; D007553:Isotope Labeling; D008279:Magnetic Resonance Imaging / Q000379:methods*; D059346:Magnets / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D011522:Protons
chemical_list: D011522:Protons; C118638:glycol-chitosan; D005461:Fluorine; D048271:Chitosan
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