ine IgG1 kappa monoclonal antibody directed against the CD20 antigen.
Ibritumomab tiuxetan is a clear, colorless, sterile, pyrogen-free, preservative-free solution that may contain translucent particles. Each single-use vial includes 3.2 mg of ibritumomab tiuxetan in 2 mL of 0.9% Sodium Chloride.
Physical/Radiochemical Characteristics of In-111
Indium-111 decays by electron capture, with a physical half-life of 67.3 hours (2.81 days). The product of radioactive decay is non-radioactive Cadmium-111. Radiation emission data for In-111 are summarized in Table 5.
Table 5. Principal In-111 Radiation Emission Data Radiation Mean % per
Disintegration Mean
Energy (keV)
Gamma-2 90.2 171.3
Gamma-3 94.0 245.4
External Radiation
The exposure rate constant for 1 mCi (37 MBq) of In-111 is 8.3 x 10-4 C/kg/hr (3.2 R/hr) at 1 cm.
To allow correction for physical decay of In-111, the fractions that remain at selected intervals before and after the time of calibration are shown in Table 6.
Table 6. Physical Decay Chart: In-111 Half-life 2.81 Days (67.3 Hours) Calibration Time (Hrs.) Fraction Remaining
-48 1.64
-42 1.54
-36 1.45
-24 1.28
-12 1.13
-6 1.06
0 1.00
6 0.94
12 0.88
24 0.78
36 0.69
42 0.65
48 0.61
Physical/Radiochemical Characteristics of Y-90
Yttrium-90 decays by emission of beta particles, with a physical half-life of 64.1 hours (2.67 days). The product of radioactive decay is non-radioactive Zirconium-90. The range of beta particles in soft tissue (χ90) is 5 mm. Radiation emission data for Y-90 are summarized in Table 7.
Table 7. Principal Y-90 Radiation Emission Data Radiation Mean % per
Disintegration Mean
Energy (keV)
Beta minus 100 750-935
External Radiation
The exposure rate for 1 mCi (37 MBq) of Y-90 is 8.3 x 10-3 C/kg/hr (32 R/hr) at the mouth of an open Y-90 vial.
To allow correction for physical decay of Y-90, the fractions that remain at selected intervals before and after the time of calibration are shown in Table 8.
Table 8. Physical Decay Chart: Y-90 Half-life 2.67 Days (64.1 Hours) Calibration Time (Hrs.) Fraction Remaining Calibration Time (Hrs.) Fraction Remaining
-36 1.48 0 1.00
-24 1.30 1 0.99
-12 1.14 2 0.98
-8 1.09 3 0.97
-7 1.08 4 0.96
-6 1.07 5 0.95
-5 1.06 6 0.94
-4 1.04 7 0.93
-3 1.03 8 0.92
-2 1.02 12 0.88
-1 1.01 24 0.77
0 1.00 36 0.68
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Ibritumomab tiuxetan binds specifically to the CD20 antigen (human B-lymphocyte-restricted differentiation antigen, Bp35). The apparent affinity (KD) of ibritumomab tiuxetan for the CD20 antigen ranges between approximately 14 to 18 nM. The CD20 antigen is expressed on pre-B and mature B lymphocytes and on > 90% of B-cell non-Hodgkin’s lymphomas (NHL). The CD20 antigen is not shed from the cell surface and does not internalize upon antibody binding.
The chelate tiuxetan, which tightly binds In-111 or Y-90, is covalently linked to ibritumomab. The beta emission from Y-90 induces cellular damage by the formation of free radicals in the target and neighboring cells.
Ibritumomab tiuxetan binding was observed in vitro on lymphoid cells of the bone marrow, lymph node, thymus, red and white pulp of the spleen, and lymphoid follicles of the tonsil, as well as lymphoid nodules of other organs such as the large and small intestines.
12.2 Pharmacodynamics
In clinical studies, administration of the Zeva lin therapeutic regi |
