THERAPEUTIC ASPECTS OF RADIOISOTOPES IN HEPATOBILIARY MALIGNANCY

Liver tumours frequently present at a late stage and only a minority of patients are likely to benefit from resection or transplantation. Inoperable tumours carry a grave prognosis. External beam irradiation of the liver is dose-limited by the radiosensitivity of hepatocytes, particularly in the presence of cirrhosis, but internal radiation using radio-isotope sources can achieve more selective irradiation of the chosen field. Sealed sources are dose-limited by their effects on surrounding tissues, whereas with unsealed sources the dose of radio-isotope administered is limited by bone marrow suppression. Iridium-192 wires are most frequently employed as a sealed intracavitary source. They may be inserted surgically, transhepatically or endoscopically. Doses of up to 60 Gy can be delivered to a malignant biliary stricture without damage to the surrounding parenchyma. The incidence of cholangitis is low if treatment is administered after insertion of an endoprosthesis. Unsealed radio-isotope sources may be injected directly into the tumour, administered embolically via the hepatic artery in the form of microspheres or lipid droplets, or given via parenteral infusion attached to tumour-specific antibodies. Of these vehicles, the lipid agent Lipiodol appears to be the most effective and can deliver a potentially lethal dose of radiation to small tumors. Host reaction to the injected antibody remains a major drawback to the use of monoclonal antibodies as targeting agents. Iodine-131 is a beta- and gamma-emitter, producing a local tumoricidal effect and allowing accurate dosimetry by means of external scintigraphy. Yttrium-90 is a pure beta-emitter with a greater maximum beta energy and cytotoxic range; however, it is retained in bony tissues, resulting in a dose-related risk of marrow suppression. Bone absorption cannot be measured by external imaging owing to the absence of gamma emission. This lack of accurate dosimetry, coupled with the toxic side-effects of yttrium treatment, make iodine-131 the current isotope of choice.