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

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

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.

Citation

De Luca, E., Harvey, P., Chalmers, K. H., Mishra, A. P., Senanayake, K., Wilson, J. I., …Parker, D. (2014). Characterisation and evaluation of paramagnetic fluorine labelled glycol chitosan conjugates for 19F and 1H magnetic resonance imaging. JBIC Journal of Biological Inorganic Chemistry, 19(2), 215-227. https://doi.org/10.1007/s00775-013-1028-y

• Journal Article Type: Article
• Publication Date: Feb 1, 2014
• Deposit Date: Jun 18, 2014
• Publicly Available Date: Jul 4, 2014
• Journal: JBIC Journal of Biological Inorganic Chemistry
• Print ISSN: 0949-8257
• Electronic ISSN: 1432-1327
• Publisher: Springer
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 2
• Pages: 215-227
• DOI: https://doi.org/10.1007/s00775-013-1028-y
• Keywords: Contrast agents, Fluorine, Tumour uptake, MRI imaging.
• Public URL: https://durham-repository.worktribe.com/output/1425093