Mixed-ligand complexes of yttrium-90 dialkyldithiocarbamates with 1,10-phenanthroline as a possible agent for therapy of hepatocellular carcinoma.

Yttrium-90 is a radioelement which has found wide use in targeted radionuclide therapy because of its attractive physical and chemical properties. Radioembolisation of hepatocellular carcinoma with radiolabelled Lipiodol is a method of choice. We have synthesised a series of alkyldithiocarbamate yttrium complexes, easily extracted into Lipiodol due to their high lipophilicity. Among the prepared series, a new radioconjugate, which is stable over an extended period of time, has been prepared, and could represent a potential treatment procedure for hepatocellular carcinoma.

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

Intra-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% (P<0.01) 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 2.1+/-0.7 with isoflurane as against 4.4+/-2.6 (P<0.05) 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.

Development and biodistribution of 188Re-SSS lipiodol following injection into the hepatic artery of healthy pigs.

Although intra-arterial radiotherapy with (131)I-labelled lipiodol is a useful therapeutic approach in the treatment of hepatocellular carcinomas, various disadvantages limit its use. Here we describe the development of (188)Re-SSS lipiodol, as well as its biodistribution in the healthy pig after injection into the hepatic artery. The (188)Re-SSS lipiodol was obtained after dissolving a chelating agent, previously labelled with (188)Re, in cold lipiodol. The radiochemical purity (RCP) of the labelling was checked immediately and at 24 and 48 h. The (188)Re-SSS lipiodol was injected into the hepatic artery of six healthy pigs. They were killed 1, 24 and 48 h post injection, for ex vivo counting. An autoradiographic study was performed in three cases. (188)Re-SSS lipiodol was obtained with a yield of 87%+/-9.1%. The immediate RCP was 93%+/-3.4%. This radiolabelling was reproducible and stable at 48 h in plasma: 90.6%+/-1.5% of the activity remained in the lipiodol with an RCP of 91%+/-4%. Ex vivo counting confirmed the predominantly hepatic uptake and revealed weak lung and intestinal uptake. There was very weak urinary elimination (2.3%+/-0.5% at 48 h) and a slightly higher level of intestinal elimination (4.8%+/-1.9% at 48 h). The autoradiographic studies showed (188)Re-SSS lipiodol to be located mainly in sinusoids, like (131)I-lipiodol. By using the method described here, (188)Re-SSS lipiodol can be obtained with a very high yield and a satisfactory RCP. Its biodistribution in the healthy pig is in agreement with data published elsewhere concerning other types of radiolabelling used for lipiodol, except for the very weak urinary and intestinal elimination, which probably indicates better stability of (188)Re-SSS labelling.