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Characterisation and evaluation of paramagnetic fluorine labelled glycol chitosan conjugates for 19F and 1H magnetic resonance imaging

Parker, David; De Luca, Elena; Botta, Mauro; Harvey, Peter; Chalmers, Kirsten H.; Mishra, Anurag; Fekete, Marianna; Blamire, Andrew M.; Senanayake, P. Kanthi; Wilson, J. Ian

Authors

David Parker

Elena De Luca

Mauro Botta

Kirsten H. Chalmers

Anurag Mishra

Marianna Fekete

Andrew M. Blamire

P. Kanthi Senanayake

J. Ian Wilson



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 (r 1p 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 19F resonance in the holmium conjugate complex using a surface coil did not succeed owing to its high R 2 value (750 Hz, 7 T). However, the fluorine signal in the dysprosium triphosphinate chitosan conjugate [R 1/R 2 = 0.6 and R 1 = 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.

Journal Article Type Article
Acceptance Date Jul 22, 2013
Online Publication Date Aug 17, 2013
Publication Date 2014-02
Deposit Date Oct 24, 2019
Journal JBIC Journal of Biological Inorganic Chemistry
Print ISSN 0949-8257
Electronic ISSN 1432-1327
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 19
Issue 2
Pages 215-227
DOI https://doi.org/10.1007/s00775-013-1028-y
Keywords Inorganic Chemistry; Biochemistry
Public URL https://nottingham-repository.worktribe.com/output/2829488
Publisher URL https://link.springer.com/article/10.1007%2Fs00775-013-1028-y