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Pretargeted Radioimmunotherapy of Cancer: Progress Step by Step^*

¹ Department of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands

View larger version (24K): [in a new window]   FIGURE 1. Schematic representation of 3-step avidin/biotin-based pretargeting. Biotinylated antitumor mAb is injected in first step. Subsequently, avidin is administered to avidinylate tumor, and in last step radiolabeled biotin is injected.

View larger version (28K): [in a new window]   FIGURE 2. Schematic representation of 5-step SA/biotin- or avidin/biotin-based pretargeting strategy. First, biotinylated mAb is injected. Then, avidin is administered to clear biotinylated mAb from circulation. Streptavidin is injected in third step to avidinylate tumor. Circulating SA is cleared with biotinylated albumin, and radiolabeled biotin is then injected.

View larger version (51K): [in a new window]   FIGURE 3. Anterior whole-body images of patient with recurrent glioma who underwent 5-step pretargeted radioimmunotherapy (2.22 MBq/m2 90Y-DOTA-biotin). 111In-DOTA-biotin (74 MBq) was coadministered to allow scintigraphic imaging. Images were acquired 1 h (left) and 22 h (right) after administration of radiolabeled biotin. On image acquired 22 h after injection, tumor is clearly visualized (arrow).

View larger version (26K): [in a new window]   FIGURE 4. Schematic representation of 3-step SA/biotin-based pretargeting strategy. mAb–SA conjugate is injected, followed by galactosylated albumin-biotin as clearing agent. In third step, radiolabeled biotin is injected.

View larger version (18K): [in a new window]   FIGURE 5. Schematic representation of 2-step bsmAb-based pretargeting strategy. Tumor is pretargeted with antihapten x antitumor F(ab')2 bsmAb. In second step, radiolabeled bivalent hapten is administered. Note bivalent binding of bivalent hapten at tumor cell surface.

View larger version (28K): [in a new window]   FIGURE 6. Scintigraphic images of nude mice with subcutaneous human renal cell carcinoma xenografts in right flank (arrows). Mice were injected intravenously with 15 µg G250 x DTIn-1 bsmAb. Three days later, mice intravenously received 10 ng of tetrapeptide substituted with 2 DTPA moieties and labeled with 1.85 MBq of 111In. Images were acquired at 1, 4, 24, and 96 h after injection (p.i.).

View larger version (72K): [in a new window]   FIGURE 7. Scintigraphic images of patient with metastasized SCLC who received 100 mg/m2 anti-DTPA x anti-CEA F(ab')2 bsmAb. Seven days later, therapeutic dose (3.7 GBq) of 131I-labeled bivalent hapten was injected. Anterior (A) and posterior (B) images obtained 5 d after injection of radiolabel clearly show accumulation of radiolabel in SCLC lesions in liver.