Patient-specific dosimetry of pretargeted radioimmunotherapy using CC49 fusion protein in patients with gastrointestinal malignancies.
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.


CONCLUSIONS
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.
Shen
Sui
S
Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Wallace Tumor Institute, Birmingham, Alabama 35294, USA. sshen@uabmc.edu
Forero
Andres
A
LoBuglio
Albert F
AF
Breitz
Hazel
H
Khazaeli
M B
MB
Fisher
Darrell R
DR
Wang
Wenquan
W
Meredith
Ruby F
RF
D000368:Aged; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D001710:Biotin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001822:Body Burden; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016499:Radioimmunotherapy / Q000379:methods*; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D012062:Relative Biological Effectiveness; D014018:Tissue Distribution
D000912:Antibodies, Neoplasm; C091202:B72.3 antibody; C405616:DOTA-biotin; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; D001710:Biotin