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Copper-67-Labeled Monoclonal Antibody Lym-1, a Potential Radiopharmaceutical for Cancer Therapy: Labeling and Biodistribution in RAJI Tumored Mice

Departments of Radiology (Nuclear Medicine) University of California, Davis, Medical Center, Sacramento, California
Chemistry Department, University of California, Davis, California

Correspondence: For reprints contact: Sally J. DeNardo, MD, Nuclear Medicine/Radiology Department, Univ. Davis Medical Center, 4301 X St., Folb Ii-E, Sacramento, CA 95817.

ABSTRACT

Copper-67 (⁶⁷Cu) is one of the most promising radiometals for radioimmunotherapy because of its 61.5 hr physical half-life, abundant beta particles, and gamma emissions suitable for imaging. However, ⁶⁷Cu is readily transferred from the usual chelates of EDTA or DTPA to albumen. We developed a new macrocycle (6-p-nitrobenzyl-TETA) to chelate copper. Bifunctional chelating agent p-bromoacetamidobenzyl-TETA was conjugated to Lym-1, a monoclonal antibody against human B cell lymphoma, without significantly altering its immunoreactivity. This conjugate was stably labeled with ⁶⁷Cu under conditions chosen to optimize the yield of a high specific activity radiopharmaceutical. The biodistribution in RAJI tumor bearing mice demonstrated significant tumor uptake (14.7% ID per gram) and extended residence time (120 hr) in contrast to normal organs. After 24 hr, radioactivity was continuously cleared from all tissues except the tumor. This study suggests ⁶⁷Cu labeled Lym-1 to be a promising radiopharmaceutical for potential use for radioimmunotherapy of B cell lymphoma.

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