PREPARATION AND BIOLOGICAL EVALUATION OF 177LU-LABELED RITUXIMAB FOR B-LYMPHOMA TREATMENT

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RADFAR EDALAT; ARBABI AZIM; SARDARI DARIUSH

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Journal: IRANIAN JOURNAL OF NUCLEAR MEDICINE Year:2010 | Volume:18 | Issue:SUPPLEMENT 1 Page(s): 14-14

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Title

PREPARATION AND BIOLOGICAL EVALUATION OF 177LU-LABELED RITUXIMAB FOR B-LYMPHOMA TREATMENT

Author(s)

RADFAR EDALAT | ARBABI AZIM | SARDARI DARIUSH

Keywords

177LU RITUXIMAB

RADIOIMMUNOTHERAPY

BIODISTRIBUTION

Abstract

Introduction: 177Lu is a beta emitter with suitable decay mode [T1/2=6.7 d, Eβmax=497 keV, EY=112keV (6.4%) & 208 keV (11%)] for using in radio therapy. Various radiolabeled monoclonal antibodies have been developed in treatment. Rituximab is a chimeric mouse-human monoclonal antibody. Rituximab binds with human B-lymphocate-restricted differentiation antigen: CD20. Rituxsimab was used successfully as an anti-CD20 radiolabeled antibody before.Methods: 177Lu was produced by thermal neutron irradiation of 1 mg of natural Lu2O3 with 4*10^13 n cm-2 s-1 neutron flux at Tehran Research Reactor. The irradiation target was dissolved in 200 mL of 1.0 M HCl, to prepare 177LuCl3. The radionuclide purity of product was measured by using ITLC and gamma spectroscopy by HPGe detector. The macrocyclic bifunctional chelating agent, N-succinimidyl-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA-NHS) was prepared at 25 C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. DOTA-Rituximab was obtained by the adding 0.5 mL of a rituximab pharmaceutical solution (10 mg/mL, in phosphate buffer, pH 7.8) to a glass tube pre-coated with DOTA-NHS (0.01–0.1 mg) at 25C with continuous mild stirring for 15 h. The stability of radiolabeled was studied in human serum. The biodistributions of 177Lu-DOTA-Rituximab and 177LuCl3 were determined for normal rats. The tissue uptakes of each injection were measured.Results: Radiolabeling was performed at 37C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of>98% at optimized conditions. The percents of Injected Dose per gram of tissue were compared in different selected times (2-168 h). The peak of uptakes for 177LuCl3 was observed in bone, liver and kidney. High uptakes of 177Lu-DOTA-Rituximab were in spleen, liver and lungs.Conclusion: The radiolabeled complex was stable in human serum at 37C for 24 h. The biodistribution of the radiolabeled antibody is in agreement with other radiolabeled antiCD20 species already reported.177Lu- DOTA-Rituximab is potential radioimmunotherapeutic agent for B-lymphoma treatment.

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APA: Copy

RADFAR, EDALAT, ARBABI, AZIM, & SARDARI, DARIUSH. (2010). PREPARATION AND BIOLOGICAL EVALUATION OF ¹⁷⁷LU-LABELED RITUXIMAB FOR B-LYMPHOMA TREATMENT. IRANIAN JOURNAL OF NUCLEAR MEDICINE, 18(SUPPLEMENT 1), 14-14. SID. https://sid.ir/paper/590471/en

Vancouver: Copy

RADFAR EDALAT, ARBABI AZIM, SARDARI DARIUSH. PREPARATION AND BIOLOGICAL EVALUATION OF ¹⁷⁷LU-LABELED RITUXIMAB FOR B-LYMPHOMA TREATMENT. IRANIAN JOURNAL OF NUCLEAR MEDICINE[Internet]. 2010;18(SUPPLEMENT 1):14-14. Available from: https://sid.ir/paper/590471/en

IEEE: Copy

EDALAT RADFAR, AZIM ARBABI, and DARIUSH SARDARI, “PREPARATION AND BIOLOGICAL EVALUATION OF ¹⁷⁷LU-LABELED RITUXIMAB FOR B-LYMPHOMA TREATMENT,” IRANIAN JOURNAL OF NUCLEAR MEDICINE, vol. 18, no. SUPPLEMENT 1, pp. 14–14, 2010, [Online]. Available: https://sid.ir/paper/590471/en

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