Pharmacokinetics and dosimetry of an alpha-particle emitter labeled antibody: Bi-213-HuM195 (anti-CD33) in patients with leukemia

Data from nine patients with leukemia participating in a phase I activity-e scalation study of HuM195, labeled with the oc-particle emitter Bi-213 (hal f-life = 45.6 min), were used to estimate pharmacokinetics and dosimetry. T his is the first trial using an a-particle emitter in humans. The linear en ergy transfer of alpha particles is several hundredfold greater than that o f beta emissions. The range in tissue is approximately 60-90 mu m Methods: The activity administered to patients ranged from 0.6 to 1.6 GBq. Patient i maging was initiated at the start of each injection, Thirty 1-min images fo llowed by ten 3-min images were collected in dynamic mode; a 20% photopeak window centered at 440 keV was used. Blood samples were collected until 3 h postinjection and counted in a gamma counter. Contours around the liver an d spleen were:drawn on the anterior and posterior views and around a portio n of the spine on the posterior views. No other organs were visualized. Res ults: The percentage injected dose in the liver and spleen volumes increase d rapidly over the first 10-15 min to a constant value for the remaining ho ur of imaging, yielding a very rapid uptake followed by a plateau in the an tibody uptake curves, The kinetic curves were integrated to yield cumulated activity. The mean energy emitted per nuclear transition for Bi-213 and it s daughters, adjusted by a relative biologic effectiveness of 5 for alpha e missions, was multiplied by the cumulated activity to yield the absorbed do se equivalent, Photon dose to the total body was determined by calculating a photon-absorbed fraction. The absorbed dose equivalent to liver and splee n volumes ranged from 2.4 to 11.2 and 2.9 to 21.9 Sv, respectively. Marrow (or leukemia) mean dose ranged from 6.6 to 12.2 Sv. The total-body dose (ph otons only) ranged from 2.2 x 10(-4) to 5.8 x 10-4 Gy, Conclusion: This stu dy shows that patient imaging of Bi-213, an alpha-particle emitter, labeled to HuM195 is possible and may be used to derive pharmacokinetics and dosim etry; The absorbed dose ratio between marrow, liver and spleen volumes and the whole body for Bi-213-HuM195 is 1000-fold greater than that commonly ob served with beta-emitting radionuclides used for radioimmunotherapy.