Abstract
In order to use Auger-electron therapeutic effects in CD20 antigen targeting in lymphomas, Mabthera™ (rituximab) was successively labeled with [111In]-indium chloride (185 MBq) after conjugation with freshly prepared macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) and ccDTPA separately. Conjugated-Rituximab was obtained by the addition of 1 ml of a rituximab pharmaceutical solution (5 mg/ml, in phosphate buffer, pH=7.8) to a glass tube pre-coated with freshly prepared DOTA-NHS or ccDTPA (0.01-0.1 mg) at 25°C. Radiolabeling was performed at 37°C in 3h and room temperature for one hour for DOTA-conjugate and DTPA-conjugate respectively. HPLC showed an overall radiochemical purity of 97.5 and 95% for DOTA and DTPA-conjugates respectively (Specific activity =2800-5600 GBq/mM). The final isotonic 111In-rituximab complexes were checked by gel electrophoresis for radiolysis. Preliminary biodistribution studies in normal rat model performed to determine radioimmunoconjugates distribution of up to 48h.
Highlights
Several studies of radiolabeled anti-CD20 monoclonal antibodies at nonmyeloablative doses in treating B-cell NHL have been reported, and several are in progress
Rituximab has been labeled for metabolism and localization of CD20 antigens throughout the body and/or penetration of the antibody to specific organs [5]
A precise labeling strategy was employed using freshly-prepared DOTA-NHS and ccDTPA and optimized radiolabeling methods for developing highly reactive conjugated anti-CD20 for radiometal studies has been has been introduced for diagnosis and therapy purposes
Summary
Several studies of radiolabeled anti-CD20 monoclonal antibodies at nonmyeloablative doses in treating B-cell NHL have been reported, and several are in progress. A precise labeling strategy was employed using freshly-prepared DOTA-NHS and ccDTPA and optimized radiolabeling methods for developing highly reactive conjugated anti-CD20 for radiometal studies has been has been introduced for diagnosis and therapy purposes. The conjugated DOTA-rituximab fractions containing the maximum protein content were labeled with 111In-InCl3 solution.
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