Description and technical pitfalls of a hepatoma model and of intra-arterial injection of radiolabelled lipiodol in the rat

Abstract

SummaryIntra-arterial metabolic radiotherapy (using lipiodol labelled with iodine-131 or rhenium-188) is a therapeutic approach that can be used for the treatment of hepatocellular carcinomas (HCC). We propose a detailed description of the tumoral model using the N1-S1 cell line as well as a technique for intra-arterial injection of radiolabelled lipiodol in order to undertake preclinical studies necessary for the evaluation of a new molecule. We also report the principal technical pitfalls that were faced. The speed of injection of the tumoral cells is a key factor in the tumoral induction since slow injections lead to a tumoral induction rate of 36.3% compared with 76.6% (Po0.01) when using very slow injections. This parameter should thus be controlled carefully during the subcapsular injection of the tumoral cells. In addition, when injecting radiolabelled lipiodol, anaesthesia should not be performed with isoflurane since this leads to a reduction in tumoral uptake. Indeed, we found a 'tumour/ healthy liver' uptake ratio of only 2.170.7 with isoflurane as against 4.472.6 (Po0.05) when anaesthesia was carried out by intraperitoneal injection of ketamine. Lastly, we show that the tumour size has an influence on the tumoral uptake of radiolabelled lipiodol; therefore, this parameter must also be carefully controlled.

Evaluation of plasma carcinogenic markers in rat hepatic tumors models induced by rat hepatoma N1-S1 cells and benzo[a]pyrene

“…N1-S1 cells, originally established in cell culture from a Novikoff hepatocarcinoma in a rat (Garin et al, 2005), were obtained from the American Type Culture Collection (ATCC) and used for tumor induction. N1-S1 cells were routinely cultured in MEM + 10% FBS, 4 mM glutamine, 50 µg/mL streptomycin, and 100 IU/mL penicillin G. Cells were grown at 37 o C under a 5% CO 2 atmosphere.…”

Poly(lactide-co-glycolide) microspheres for MRI-monitored transcatheter delivery of sorafenib to liver tumors

“…Sham control and treatment rats both underwent procedures to invasively catheterize the proper hepatic artery ([24, 25]). The catheterization procedure involved surgically exposing the portal triad above the first loop of the duodenum.…”

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“…N1-S1 tumors are also produced through intra-hepatic injection of syngeneic tumor cells. The advantage of this model includes the ability to generate concurrent liver cirrhosis through common bile duct ligation, [25] while it is limited by suboptimal tumor induction rates, [26] and potential for spontaneous regression. [22] Recently, a DEN-induced Wistar rat autochthonous HCC model was developed ( Figure 2).…”