Intra-hepatic-arterial infusion of misonidazole – an experimental study of regional radiosensitisation by intraarterial embolisation

Abstract

Summary The purpose of this study was to generate a selective radiosensitising effect by the intra-hepaticarterial infusion of misonidazole (MISO). MISO (10 mg) was infused after transcatheter hepatic-arterial embolisation into the livers of rabbits bearing VX2 liver cancer. This procedure was followed by 15 Gy electron irradiation. Evaluation of tumour volume and histological examination was carried out on the 7th day after treatment. The greatest tumour response was obtained in the group which received MISO followed by radiation and was characterised by extensive fibrosis around the tumour and nearly complete tumour necrosis. Liver cell regeneration was also noted in adjacent liver tissue. . In view of this, we have carried out a study to determine the possibility of obtaining a selective radiosensitising effect by intra-hepatic arterial infusion of misonidazole (MISO), an agent which has been shown to display a steep dose-response for radiosensitisation but also for neurotoxicity. Encouraging results have been obtained by regional administration of 10 mg MISO to rabbits bearing liver tumours and treated with 15 Gy of electron irradiation. Materials and methodsTwenty-two male New Zealand white rabbits weighing 2.0-2.5 kg were used. The VX2 tumour cell line was maintained by serial transplantation into the hind leg muscle. The rabbits were anesthetised by injection of thiopentalum natricum (20 mg kg-1, i.v.) for laparotomy and finely minced fragments of tumour were inoculated into the left medial hepatic lobes. Fourteen days after inoculation the tumours were 2.0-2.5 cm in diameter as measured from CT scans, accordingly the operation for transcatheter hepatic-arterial embolisation was performed on the 14th day after the tumour inoculation under sodium pentobarital anesthesia (30 mg kg-', i.v.). A longitudinal incision along the right inner inguinal was made, exposing the right femoral artery. A 2 F polyethylene guiding catheter connected to a 1 ml syringe was inserted via a very small incision into the artery, the position of the guiding cathether being monitored angiographically by the injection of 60% Urografin under fluoroescopic control. The final, critical positioning of the catheter was made when the tip of the catheter reached the space between the 12th thoracic vertebra and the first lumbar vertebra, thereby making certain that the entry of contrast agent into the hepatic-artery was after any arterial divisions. Microspheres were then injected. An angiograph of rabbit common hepatic artery is shown in Figure 1. Injection of the agents after selective catheterisation was monitored under fluoroscopy to avoid movement of the catheter tip.Macroaggregated albumin (MAA) microspheres, 20-50#m in diameter with cross-linked configuration, were chosen for embolisation. They were suspended in normal saline at a concentration of 3 x 106/0.5 ml for each animal. MISO was dissolved in normal saline in a 35'C water bath just before infusion. Five groups were used: (1) control (n = 5), 1.0 ml normal saline was injecte...

Effects of Repeated Transcatheter Arterial Embolization in Patients with Hepatocellular Carcinoma

“…This is observed at the same rate parallel to clinical and radiological responses. As chemotherapeutic agents 20-50 mg doxorubicin, 4-20 mg mitomycin C, 50-60 mg epirubicin (Farmorubicine), and 100 mg cisplatin were used [2,4,6,7,9,11,[14][15][16][17], These agents can be used either alone or in combi nation. In our study in order to obtain a wider anticancer effect, we preferred to use the cisplatin -mitomycin C combination.…”

“…Doses of 50-75 mg (1 mg/kg) cisplatin, of 15 mg mitomycin C, and of 5 cm3 Lipiodol were administered. In many studies, when used alone, Lipiodol is proven to be more effective; therefore, Gclfoam is used additionally for embolization [1][2][3][4]. Nine patients were supcrsclcctivcly cathctcrized from the right and 6 from the left arteria hepatica.…”