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Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies

¹ Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama
² Department of Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama
³ NeoRx Corp., Seattle, Washington
⁴ Pacific Northwest National Laboratory, Richland, Washington
⁵ Biostatistics Division, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama

Pretargeted radioimmunotherapy (RIT) using CC49 fusion protein, comprised of CC49-(scFv)₄ and streptavidin, in conjunction with ⁹⁰Y/¹¹¹In-DOTA-biotin (DOTA = dodecanetetraacetic acid) provides a new opportunity to improve efficacy by increasing the tumor-to-normal tissue dose ratio. To our knowledge, the patient-specific dosimetry of pretargeted ⁹⁰Y/¹¹¹In-DOTA-biotin after CC49 fusion protein in patients has not been reported previously. Methods: Nine patients received 3-step pretargeted RIT: (a) 160 mg/m² of CC49 fusion protein, (b) synthetic clearing agent (sCA) at 48 or 72 h later, and (c) ⁹⁰Y/¹¹¹In-DOTA-biotin 24 h after the sCA administration. Sequential whole-body ¹¹¹In images were acquired immediately and at 2–144 h after injection of ⁹⁰Y/¹¹¹In-DOTA-biotin. Geometric-mean quantification with background and attenuation correction was used for liver and lung dosimetry. Effective point source quantification was used for spleen, kidneys, and tumors. Organ and tumor ⁹⁰Y doses were calculated based on ¹¹¹In imaging data and the MIRD formalism using patient-specific organ masses determined from CT images. Patient-specific marrow doses were determined based on radioactivity concentration in the blood. Results: The ⁹⁰Y/¹¹¹In-DOTA-biotin had a rapid plasma clearance, which was biphasic with <10% residual at 8 h. Organ masses ranged from 1,263 to 3,855 g for liver, 95 to 1,009 g for spleen, and 309 to 578 g for kidneys. The patient-specific mean ⁹⁰Y dose (cGy/37 MBq, or rad/mCi) was 0.53 (0.32–0.78) to whole body, 3.75 (0.63–6.89) to liver, 2.32 (0.58–4.46) to spleen, 7.02 (3.36–11.2) to kidneys, 0.30 (0.09–0.44) to lungs, 0.22 (0.12–0.34) to marrow, and 28.9 (4.18–121.6) to tumors. Conclusion: Radiation dose to normal organs from circulating radionuclide is substantially reduced using pretargeted RIT. Tumor-to-normal organ dose ratios were increased about 8- to 11-fold compared with reported patient-specific mean dose to liver, spleen, marrow, and tumors from ⁹⁰Y-CC49.

Key Words: gastrointestinal cancer • dosimetry • pretargeted radioimmunotherapy

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