Lewis, J.S. and Dearling, J.L.J. and Sosabowski, J.K. and Zweit, J. and Carnochan, P. and Kelland, L.R. and Coley, H.M. and Blower, P.J. (2000) Copper bis(diphosphine) complexes: radiopharmaceuticals for the detection of multi-drug resistance in tumours by PET. European Journal of Nuclear Medicine, 27 (6). pp. 638-646. ISSN 0340-6997.
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Experience with imaging of the multi-drug resistance (MDR) phenotype in rumours using technetium-99m sestamibi, a substrate of the P-glycoprotein (Pgp) transporter, suggests that better quantification of images and separation of MDR from other variables affecting tracer uptake in tumours are required. One approach to these problems is the development of short half-lift positron-emitting tracers which are substrates of Pgp. Several lipophilic cationic copper(I) bis(diphosphine) complexes labelled with copper-64 have been synthesised and evaluated in vitro as substrates for Pgp. The synthesis is rapid and efficient with no need for purification steps. The chemistry is suitable fur use with very short half-lift: radionuclides such as copper-62 (9.7 min) and copper-60 (23.7 min). Incubation of the complexes with human serum in vitro showed that they are sufficiently stable in serum to support clinical imaging, and the more lipophilic members of the series are taken up rapidly by cells (Chinese hamster ovary and human ovarian carcinoma) in vitro with great avidity. Uptake in human ovarian carcinoma cells is significantly reduced after several months of conditioning in the presence of doxorubicin, which induces increased Pgp expression. Uptake in hooded rat sarcoma (HSN) cells, which express Pgp, is significantly increased in the presence of the MDR modulator cyclosporin A. Biodistribution studies in hooded rats show rapid blood clearance, excretion through both kidneys and liver, and low uptake in other tissues. The one complex investigated in HSN tumour-bearing rats showed uptake in tumour increasing up to 30 min p.i. while it was decreasing in other tissues. for development of radiopharmaceuticals containing copper radionuclides, and that this series of complexes should undergo further evaluation in vivo as position emission tomography imaging agents fur MDR.
|Uncontrolled keywords:||copper-64; multi-drug resistance; diphosphines; positron emission tomography; tumour|
|Divisions:||Faculties > Science Technology and Medical Studies > School of Engineering and Digital Arts
Faculties > Science Technology and Medical Studies > Centre for Music Technology
|Depositing User:||O.O. Odanye|
|Date Deposited:||02 Apr 2009 11:37|
|Last Modified:||25 Apr 2012 10:16|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/16319 (The current URI for this page, for reference purposes)|
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