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Copper-64-Labeled Antibodies for PET Imaging

Division of Radiation Sciences, Washington University Medical School, St. Louis, Missouri
Department of Surgery, Jewish Hospital, St. Louis, Missouri
University of Missouri Research Reactor, Columbia, Missouri
Department of Chemistry, University of California, Davis, Davis, California

Correspondence: For reprints contact: Michael J. Welch, PhD, Division of Radiation Sciences, Washington University School of Medicine, Box 8131, 510 S. Kingshighway Blvd., St. Louis, MO 63110.

ABSTRACT

In the imaging of tumors using radiolabeled monoclonal antibodies, the use of PET gives increased sensitivity over conventional gamma camera imaging techniques. Copper-64, a positron-emitting radionuclide, has been labeled to 1A3, an anticolorectal carcinoma monoclonal antibody, and its fragments 1A3-F(ab')₂ utilizing the bifunctional chelate Br-benzyl-TETA. The ⁶⁴Cu-labeled intact 1A3 and 1A3-F(ab')₂ have been evaluated as potential imaging agents for PET. Biodistribution studies of ⁶⁴Cu-benzyl-TETA-1A3 and ⁶⁴Cu-benzyl-TETA-1A3-F(ab')₂ in tumor-beating hamsters were compared with those of ¹¹¹In-BrHBED-1A3, ¹¹¹In-BrHBED-1A3-F(ab')₂ and ¹²⁵I-labeled intact 1A3 and 1A3-F(ab')₂. Tumor uptake of ⁶⁴Cu-labeled intact 1A3 and fragments in the hamster model was superior to both ¹¹¹In- and ¹²⁵I-labeled intact 1A3 and fragments. Human dosimetry data for ⁶⁴Cu- and ¹²³I-labeled 1A3 and 1A3-F(ab')₂ were calculated from biodistribution data in rats. High kidney uptake of ⁶⁴Cu-benzyl-TETA-1A3-F(ab')₂ precludes clinical study at this time; however, the data shows that ⁶⁴Cu-benzyl-TETA-1A3 would be suitable for positron tomography imaging of colorectal cancer in patients.

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