ORIGINAL PAPER Characterisation and evaluation of paramagnetic fluorine labelled glycol chitosan conjugates for 19 F and 1 H magnetic resonance imaging Elena De Luca • Peter Harvey • Kirsten H. Chalmers • Anurag Mishra • P. Kanthi Senanayake • J. Ian Wilson • Mauro Botta • Marianna Fekete • Andrew M. Blamire • David Parker Received: 24 June 2013 / Accepted: 22 July 2013 Ó SBIC 2013 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 A ˚ 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 per- meation 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 com- plexes, respectively. The gadolinium conjugate was pre- pared 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 triphosph- inate 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 lmol/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. Par- allel experiments observing the 19 F resonance in the hol- mium 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 shar- per and could be observed in vivo at -65.7 ppm, following intravenous tail vein injection of a dose of 34 lmol/kg. Keywords Contrast agents Á Fluorine Á Tumour uptake Á MRI Á Imaging Abbreviations DO3A 1,4,7-Tricarboxymethyl-1,4,7,10- tetraazacyclododecane GPC Gel permeation chromatography MRI Magnetic resonance imaging MS Mass spectrometry NMM N-Methylmorpholine NMRD Nuclear magnetic relaxation dispersion TBTU Tetramethyluronium tetrafluoroborate PDI Polydispersity index MRSI Magnetic resonance spectroscopic imaging Introduction Fluorine magnetic resonance imaging (MRI) has been promoted as an alternative to proton MRI or magnetic resonance spectroscopic imaging, owing to the 100 % Responsible Editor: Valerie C. Pierre. Electronic supplementary material The online version of this article (doi:10.1007/s00775-013-1028-y) contains supplementary material, which is available to authorized users. E. De Luca Á P. Harvey Á K. H. Chalmers Á A. Mishra Á P. K. Senanayake Á D. Parker (&) Department of Chemistry, Durham University, South Road, Durham DH1 3LE, UK e-mail: david.parker@durham.ac.uk J. I. Wilson Á A. M. Blamire Northern Institute for Cancer Research, and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK M. Botta Á M. Fekete Dipartimento di Scienze e Innovazione Tecnologica, Universita ` del Piemonte Orientale ‘‘Amedeo Avogadro’’, Viale Teresa Michel 11, 15121 Alessandria, Italy 123 J Biol Inorg Chem DOI 10.1007/s00775-013-1028-y