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Residualizing Iodine Markedly Improved Tumor Targeting Using Bispecific Antibody-Based Pretargeting

¹ Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
² Department of Urology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
³ Ludwig Institute for Cancer Research, New York, New York
⁴ Immunomedics, Inc., Morris Plains, New Jersey
⁵ Center for Molecular Medicine and Immunology, Garden State Cancer Center, Belleville, New Jersey

View larger version (9K): [in a new window]   FIGURE 1. Uptake and retention of dual-labeled bivalent peptides in SK-RC-52 tumors. Tumor-bearing mice received 6 ng radiolabeled peptides, 72 h after pretargeting tumors with 15 µg bs-mAb G250xDTIn-1. (A) 125I-L-a.a. peptide () and 125I-D-a.a. peptide (•). (B) 111In-L-a.a. peptide () and 111In-D-a.a. peptide (). Biodistribution was determined 4, 24, 48, and 72 h after injection and 7 d after injection Uptake is expressed as %ID/g (mean ± SD).

View larger version (17K): [in a new window]   FIGURE 2. Biodistribution of radiolabeled bivalent peptides: 111In-L-a.a. peptide (A), 111In-D-a.a. peptide (B), 125I-L-a.a. peptide (C), and 125I-D-a.a. peptide (D). After pretargeting of SK-RC-52 tumor-bearing mice with 15 µg bs-mAb G250xDTIn-1, 72 h later mice were injected intravenously with 6 ng peptide. Mice were killed at various time points after injection of radiolabel and biodistribution was determined. Uptake is expressed as %ID/g (mean ± SD).

View larger version (14K): [in a new window]   FIGURE 3. Biodistribution of 111In label (A) and 125I label (B) in tumor-bearing mice, pretargeted with 15 µg 111In-/125I-labeled bs-mAb G250xDTIn-1. Seventy-two hours later, 2 groups of mice were injected intravenously with 6 ng bivalent peptide (groups 3 and 4, DTPA chelates loaded with unlabeled indium). Mice were killed at various time points after injection of radiolabel (Table 1) and biodistribution was determined. Uptake is expressed as %ID/g (mean ± SD).