PNNL

Abstract

Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies. Shen S, Forero A, Lobuglio AF, Breitz H, Khazaeli MB, Fisher DR, Wang W, Meredith RF. Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, and Radioisotopes Program at Pacific Northwest National Laboratory, Richland, Washington. Pretargeted radioimmunotherapy (RIT) using CC49 fusion protein, comprised of CC49-(scFv)(4) and streptavidin, in conjunction with (90)Y/(111)In-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 (90)Y/(111)In-DOTA-biotin after CC49 fusion protein in patients has not been reported previously. METHODS: Nine patients received 3-step pretargeted RIT: (a) 160 mg/m(2) of CC49 fusion protein, (b) synthetic clearing agent (sCA) at 48 or 72 h later, and (c) (90)Y/(111)In-DOTA-biotin 24 h after the sCA administration. Sequential whole-body (111)In images were acquired immediately and at 2-144 h after injection of (90)Y/(111)In-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 (90)Y doses were calculated based on (111)In 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 (90)Y/(111)In-DOTA-biotin had a rapid plasma clearance, which was biphasic with