In-vivo Microdialysis Study of the Distribution of Cisplatin into Brain Tumour Tissue after Intracarotid Infusion in Rats With 9L Malignant Glioma

Abstract

Simultaneous brain microdialysis in tumour and non-tumour tissues has been used for kinetic determination of the local distribution of an anticancer agent, cisplatin, in rats. Rat brain was implanted with 9L malignant glioma and cisplatin (3.5 mg kg-1) was administered as a selective intracarotid infusion for 30 min to rats prepared for brain microdialysis. The amount of platinum in the dialysate collected from tumour and non-tumour brain tissues was determined by atomic absorption spectrophotometry, as representative of cisplatin. Total and free platinum concentrations in plasma were also measured. Free platinum is accumulated preferentially in the tumour tissue and the brain tumour distribution coefficient (the ratio of brain tumour platinum AUC to plasma free platinum AUC, where AUC is the area under the platinum concentration-time curve) was 0.69, although there was little distribution into normal brain tissue. Drug binding to plasma proteins was 65%. It is concluded that simultaneous microdialysis is an easy and available method for assessing in-vivo local pharmacokinetics and distribution of cisplatin in tumour and non-tumour tissues of the brain.

In vivomonitoring of the transfer kinetics of trace elements in animal brains with hyphenated inductively coupled plasma mass spectrometry techniques

“…Furthermore, the higher atom density and longer residence time in the graphite tube improve ETAAS detection limits by a factor of up to 1,000-fold-down to the submicrogram-per-liter range-compared to flame AAS. In view of its advantages, several on-line and off-line methods based on the combination of microdialysis sampling and ETAAS have been developed for in vivo determination of Zn, Mn, Cu, Fe, and Pt (cisplatin) (Nakashima et al, 1997;Tokunaga et al, 2000;Leveque et al, 2001Leveque et al, , 2003Lin et al, 2004Yang et al, 2004). Because only small-volume microdialysates that contain very low concentrations of analyte ions are required for analyses, and because it always takes a long time to collect the data for biokinetics studies for in vivo animal experiments, the resulting reduction in contamination and losses of analyte species and minimized complexity of the operation procedures are key factors that lead to the attractiveness of in vivo determination of trace metal ions.…”

Microdialysis: an in vivo approach for measuring drug delivery in oncology

“…These have assessed time versus concentration profiles of established antineoplastic agents such as methotrexate (MTX) [25,26,28,29,30,34], 5-fluorouracil (5-FU) [32], and cisplatin [27] as well as more novel compounds such as topotecan [33] and bioreductive antineoplastic agents [24]. In practically all tumor models there is a high interindividual variability in intratumoral drug distribution and a lack of correlation between drug concentrations in the plasma and tumor compartment.…”

“…Preclinical PK studies have focused principally on the description of drug PK in various tumor models including human xenotransplants in rats [24,25,26,27,28,29,30,31], mice [32,33], and rabbits [34]. These have assessed time versus concentration profiles of established antineoplastic agents such as methotrexate (MTX) [25,26,28,29,30,34], 5-fluorouracil (5-FU) [32], and cisplatin [27] as well as more novel compounds such as topotecan [33] and bioreductive antineoplastic agents [24].…”

The blood-brain and blood-tumor barriers: A review of strategies for increasing drug delivery

“…It can be used to both sample and deliver drugs to the surrounding tissue and has been used to sample extracellular drug concentrations in experimental brain tumors (Devineni et al, 1996;Nakashima et al, 1997). The principle features of microdialysis, when used as a drug delivery methodology, are that the tissue concentrations are a function of the drug concentration in the dialysate (which places control of the concentration in hands of the user) and that distribution of drug away from the dialysis catheter occurs by diffusion (Dykstra et Neuro-Oncology n JA NUA RY 2 0 0 0 52 D.R.…”