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PubMed2004

Ongoing trials with yttrium 90-labeled ibritumomab tiuxetan in patients with non-Hodgkin's lymphoma.

Targeted radiation therapy or radioimmunotherapy has been an important recent advance in the treatment of patients with B-cell non-Hodgkin's lymphoma (NHL). Yttrium 90-labeled ibritumomab tiuxetan (Zevalin) comprises the murine monoclonal antibody ibritumomab, the linker chelator tiuxetan, and the radiolabeled isotope yttrium 90. Yttrium 90 ibritumomab tiuxetan has been shown to be efficacious in the treatment of B-cell NHL. Initial phase I/II trials established the therapeutic dose of ibritumomab tiuxetan for low-grade NHL to be 0.4 mCi/kg, or 0.3 mCi/kg for patients with mild thrombocytopenia. Currently, there are many ongoing trials of ibritumomab tiuxetan with different dose schedules and dose intensities in combination with chemotherapy and autologous or allogeneic stem cell transplantation in an attempt to improve response rate and duration and to study its effectiveness in other B-cell lymphomas including mantle cell lymphoma, and chronic lymphocytic leukemia. This article reviews the ongoing trials with 90Y ibritumomab tiuxetan. Radioimmunotherapy has great promise, and the safe incorporation of 90Y ibritumomab tiuxetan into treatment will hopefully result in improved survival for patients with NHL.

Antibodies, Monoclonal↗
PubMed1988

Effects of hepatic arterial yttrium 90 glass microspheres in dogs.

A 22-micron glass microsphere called TheraSphere (Theragenics Corp., Atlanta, GA) has been developed in which yttrium 89 oxide is incorporated into the glass matrix and is activated by neutron bombardment to form the beta-emitting isotope yttrium 90 (Y 90) before using the spheres as radiotherapeutic vehicles. The injection of up to 12 times (on a liver weight basis) the anticipated human dose of nonradioactive TheraSphere into the hepatic arteries of dogs was well tolerated and produced clinically silent alterations within centrolobular areas. The hepatic arterial (HA) injection of radioactive TheraSphere also produced portal changes similar to those observed in humans after external beam therapy. While the extent of damage increased with the delivered dose, radiation exposures in excess of 30,000 cGy did not cause total hepatic necrosis and were compatible with survival. No microspheres distributed to the bone marrow and absolutely no myelosuppression was encountered in any animal. Proposed hepatic exposures to humans of 5000 to 10,000 cGy by means of these microspheres, therefore, would appear to be feasible and tolerable. Radiotherapeutic microsphere administration preceded by regional infusion of a radiosensitizing agent and/or immediately following the redistribution of blood flow toward intrahepatic tumor by vasoactive agents can potentially yield a synergistic, highly selective attack on tumors confined to the liver.

Animals↗
PubMed2004

A single treatment of yttrium-90-labeled CHX-A"-C6.5 diabody inhibits the growth of established human tumor xenografts in immunodeficient mice.

Antitumor diabody molecules are noncovalent single-chain Fv dimers that recapitulate the divalent binding properties of native IgG antibodies. Diabodies are capable of substantial accumulation in tumor xenografts expressing relevant antigens in immunodeficient mouse models. With a Mr of approximately 55,000, diabodies are rapidly cleared from the circulation, resulting in tumor-to-blood ratios that significantly exceed those achieved early after the administration of monoclonal antibodies. We have evaluated the therapeutic potential of the beta-emitting isotope yttrium-90 (t1/2, 64 hours) conjugated to the C6.5K-A diabody that specifically targets the HER2/neu human tumor-associated antigen. We have found that a single intravenous dose of 150 microCi (200 microg) 90Y-CHX-A"-C6.5K-A diabody substantially inhibits the growth rates of established MDA-361/DYT2 human breast tumor xenografts in athymic nude mice. In contrast, 300 microCi (300 microg) 90Y-CHX-A"-C6.5K-A diabody resulted in only a minor delay in the growth of SK-OV-3 human ovarian cancer xenografts. The maximum tolerated dose was also dependent on the tumor xenograft model used. These studies indicate that genetically engineered antitumor diabody molecules can be used as effective vehicles for radioimmunotherapy.

Animals↗