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Transport kinetics of four- and six-coordinate platinum compounds in the multicell layer tumour model.

Abstract：

:Four-coordinate (Pt(II)) platinum-based anticancer drugs are widely used in primary or palliative chemotherapy and produce considerable efficacy in certain clinical applications, for example testicular cancer. However, in many cancers the Pt(II) drugs are beset by poor efficacy mainly due to suboptimal pharmacokinetic properties. Consequently, the six-coordinate (Pt(IV)) class of Pt drugs were developed to improve platinum efficacy by (i) increasing stability, (ii) reducing reactivity, (iii) increasing lipophilicity, and (iv) nuclear targeting. However, comparatively little information is available on the pharmacokinetic properties of these compounds within solid tumour tissue. In the present study, the distribution and fluxes of [(14)C]-labelled [PtCl(2)(en)] (where en stands for ethane-1,2-diamine) and cis,trans-[PtCl(2)(OH)(2)(en)] drugs were determined in the multicell layer (MCL) tumour model comprising colon cancer cells. Flux data were analysed by mathematical modelling of drug diffusion and cellular uptake in the transport system. The flux of the Pt(IV) compound through the MCL was not significantly different to that of the Pt(II) drug nor were the diffusion coefficient or tissue uptake; the latter confirmed with elemental imaging analysis by synchrotron radiation induced X-ray emission. However, the flux of the Pt(IV) through the MCL was increased by hydrostatic pressure, thereby demonstrating the potential to target cancer cells further away from the vessels with six-coordinate platinum drugs.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Modok S,Scott R,Alderden RA,Hall MD,Mellor HR,Bohic S,Roose T,Hambley TW,Callaghan R

doi

10.1038/sj.bjc.6603854

subject

Has Abstract

pub_date

2007-07-16 00:00:00

pages

194-200

issue

2

eissn

0007-0920

issn

1532-1827

pii

6603854

journal_volume

97

pub_type

杂志文章

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