High-resolution single-photon emission computed tomography and X-ray computed tomography imaging of Tc-99m-labeled anti-DR5 antibody in breast tumor xenografts

Academic Article

Abstract

  • A murine, apoptosis-inducing monoclonal antibody (mTRA-8) targeting human DR5 was radiolabeled with Tc-99m. The binding affinity (Kd) and the number of DR5 receptors were measured in MD MBA-231-derived 2LMP cell lines that were "sensitive" or "resistant" to mTRA-8 killing. Single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) evaluated the Tc-99m-mTRA-8 retention and distribution within xenograft tumors; biodistribution analyses confirmed the levels. Scatchard assays showed specific and high binding affinity of Tc-99m-mTRA-8 to DR5; the killing efficacy of mTRA-8 was unchanged by Tc-99m labeling. There was no significant difference between sensitive and resistant 2LMP cells for Kd values (1.5 ± 0.3 nmol/L = acid labile), or DR5 receptors (mean/cell = 11,000). SPECT/CT imaging analyses at 6 h after injection of Tc-99m-mTRA-8 revealed the second 1.5 mm shell from the surface of the mammary fat pad tumors (n = 5; 5,627 mm3) retained 12.7 ± 1.4%ID/g, higher than the other shells, with no difference between the sensitive and resistant 2LMP tumors. Binding of Tc-99m-labeled mTRA-8 in tumor was specific; excess unlabeled mTRA-8 blocked Tc-99m-mTRA-8 retention in tumor by 45%. Retention of Tc-99m-labeled isotype antibody in tumor was consistent with the blocking study, and 30% lower. These studies show that SPECT/CT imaging provided detailed distribution information of Tc-99m-labeled mTRA-8 within breast tumor xenografts. Imaging could provide a mechanism to assess DR5 modulation when DR5 therapy is combined with chemotherapy and radiation, and thereby aid in optimizing the dosing schedule. Copyright © 2007 American Association for Cancer Research.
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    Digital Object Identifier (doi)

    Author List

  • Kim H; Chaudhuri TR; Buchsbaum DJ; Wang D; Zinn KR
  • Start Page

  • 866
  • End Page

  • 875
  • Volume

  • 6
  • Issue

  • 3