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-Particle Emitter Labeled Antibody: 213Bi-HuM195 (Anti-CD33) in Patients with Leukemia
Department of Medical Physics, Radiology and Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
Pharm-Actinium, Chevy Chase, Maryland
Correspondence: For correspondence or reprints contact: George Sgouros, PhD, Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.
ABSTRACT
Data from nine patients with leukemia participating in a phase I activity-escalation study of HuM195, labeled with the 
-particle emitter 213Bi (half-life = 45.6 min), were used to estimate pharmacokinetics and dosimetry. This is the first trial using an -particle emitter in humans. The linear energy transfer of a particles is several hundredfold greater than that of ß emissions. The range in tissue is approximately 60–90 µn. Methods: The activity administered to patients ranged from 0.6 to 1.6 GBq. Patient imaging was initiated at the start of each injection. Thirty 1-min images followed 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 and spleen were drawn on the anterior and posterior views and around a portion of the spine on the posterior views. No other organs were visualized. Results: The percentage injected dose in the liver and spleen volumes increased rapidly over the first 10–15 min to a constant value for the remaining hour of imaging, yielding a very rapid uptake followed by a plateau in the antibody uptake curves. The kinetic curves were integrated to yield cumulated activity. The mean energy emitted per nuclear transition for 213Bi and its daughters, adjusted by a relative biologic effectiveness of 5 for a emissions, was multiplied by the cumulated activity to yield the absorbed dose equivalent. Photon dose to the total body was determined by calculating a photon-absorbed fraction. The absorbed dose equivalent to liver and spleen 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 (photons only) ranged from 2.2 x 10–4 to 5.8 x 10–4 Gy. Conclusion: This study shows that patient imaging of 213Bi, an -particle emitter, labeled to HuM195 is possible and may be used to derive pharmacokinetics and dosimetry. The absorbed dose ratio between marrow, liver and spleen volumes and the whole body for 213Bi-HuM195 is 1000-fold greater than that commonly observed with ß-emitting radionuclides used for radioimmunotherapy.
Key Words: radioimmunotherapy • particle • 213Bi • HuM195 • leukemia
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