Zevalin (ibritumomab tiuxetan) is an anti-CD20 murine IgG1 monoclonal antibody conjugated to the linker tiuxetan (MX-DTPA), which securely chelates 90Y for radioimmunotherapy (RIT). Zevalin is under investigation for the outpatient treatment of relapsed or refractory low-grade, follicular or CD20+ transformed B-cell NHL. The therapeutic Zevalin injection is preceded by two infusions of 250 mg/m2 rituximab, the unlabeled chimeric anti-CD20 antibody, to clear peripheral B cells and improve biodistribution of the radiolabeled antibody. The two rituximab infusions are separated by one week, with the second infusion delivered immediately prior to 90Y Zevalin injection. A unique radiolabeling kit is used to prepare the Zevalin dose which must be administered within 8 hours of the radiolabeling procedure. By preparing 90Y Zevalin on the same day as administration, radiolysis during shipping is avoided resulting in very high radiochemical purity (RCP). During four Phase I-III clinical trials, 215 -4Y Zevalin doses were prepared at 26 clinical sites. All doses were prepared and released during a 30 minute procedure performed in the treating nuclear medicine department or an affiliated radiopharmacy. Within a glass septum reaction vial, a solution of 40 mCi WY was first adjusted to pH 4 with 50 mM sodium acetate. Zevalin was then transferred to the vial, incubated for 5 minutes, and the chelating reaction was terminated with a 7.5% human serum albumin formulation buffer. DTPA within the formulation buffer binds any remaining free 90Y, thus preventing nonspecific bone uptake. The 90Y Zevalin dose met RCP release criteria for patient use if instant thin-layer chromatography revealed that > 95% of WY was securely chelated to Zevalin. Of 215 90Y Zevalin preparations, 208 (97%) met RCP release criteria. The median RCP was 98%. An additional 195 doses of 111In Zevalin were prepared for imaging and dosimetry. Of these, 193 (99%) met RCP release criteria with a median RCP value of 99%. These results demonstrate that the Zevalin radiolabeling procedure is reliable in a multicenter setting. The user-friendly radiolabeling kit allows Zevalin to be prepared and distributed for dosimetric or therapeutic use in a timely fashion on the day of injection.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - 2000|
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