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Research Paper
Single-Photon Emission Computed Tomography Imaging With a Humanized, Apoptosis-Inducing Antibody Targeting Human Death Receptor 5 in Pancreas and Breast Tumor Xenografts
Hyunki Kim, Tandra R. Chaudhuri, Donald J. Buchsbaum, Deli Wang and Kurt R. Zinn
volume 6 | issue 9
September 2007Pages: 1396 - 1402
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PURPOSE: To characterize a novel humanized, apoptosis-inducing, antibody targeting human death receptor 5 (DR5) radiolabeled with Tc-99m by in vitro assays and in vivo imaging in murine pancreatic and breast cancer models.
EXPERIMENTAL DESIGN: Cytotoxicity and binding assays were conducted with Tc-99m-labeled humanized TRA-8 (hTRA-8) using human breast (2LMP) and pancreatic (MIA PaCa-2) tumor lines. SPECT/CT studies and biodistribution analyses were performed in nude mice with these xenografted tumors to measure in vivo distribution of Tc-99m-hTRA-8. Planar imaging was conducted in cynomolgus monkeys.
RESULTS: The acid-labile and acid-stable binding affinities (Kd) of hTRA-8 for MIA PaCa-2 cells were 3.0±1.0 (mean±SE) nM and 5.1±1.4 nM, while those for 2LMP cells were 2.5±0.6 nM and 3.3±0.4 nM, respectively. DR5 receptors per MIA PaCa-2 cell averaged 8620±1920; not statistically different from the mean per 2LMP cell at 11170±4170. The distribution of Tc-99m-hTRA-8 within tumors was not uniform, the second 1.5-mm shell from the surface was highest, averaging 6.9±0.4 (MIA PaCa-2) and 6.7±0.2 (2LMP) %ID/g at 4 hours. At 6, 24, and 48 hours after Tc-99m-hTRA-8 injection, MIA PaCa-2 tumor retentions were 7.6±0.6, 18.4±1.4, and 18.3±1.0 % of injected dose per gram (%ID/g) respectively, while Tc-99m-isotype control antibody averaged 4.9±0.4 %ID/g for MIA PaCa-2 tumors at 24 hours after dosing. The planar monkey images revealed a blood-pool distribution of Tc-99m-hTRA-8, which was confirmed by blood analyses.
CONCLUSIONS: These studies demonstrate effective delivery and retention of Tc-99m-labeled humanized TRA-8 in human xenograft tumors in the first time, and support further human studies for cancer therapy.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.