title: Intrapatient consistency of imaging biodistributions and their application to predicting therapeutic doses in a phase I clinical study of 90Y-based radioimmunotherapy.
abstract: Intrapatient variation in the biodistribution of the chimeric monoclonal antibody cT84.66 was assessed in 19 patients having a variety of carcinoembryonic antigen (CEA) positive tumors. The two studies, including whole-body imaging and blood and urine specimen collections, were conducted within 14 days of each other using (111)In-cT84.66 at a fixed total protein dose of 5 mg per patient per study. An initial pretherapy infusion of (111)In-cT84.66 was administered followed by a therapy coinfusion of (111)In-ct84.66 and 90Y-cT84.66 A closed five-compartment model was used to integrate source organ activity curves as residence time inputs into the MIRDOSE3 program. Normal organ absorbed doses were estimated for 90Y-cT84.66, the corresponding radiotherapeutic agent. For the two (111)In-cT84.66 biodistributions, all data were modeled with a R2 value of between 0.72 and 1.00 with the exception of the urine data taken during therapy. This was due to the need of diethylenetriaminepentaacetic acid during the therapy phase because of the possibility that yttrium might escape from the chelator attached to the antibody. With the assurance that the biodistributions were reproducible, we were able to estimate the 90Y-cT84.66 absorbed doses on a per-patient basis. Concordance coefficients showing the agreement between the imaging and therapy phase dose estimates were between the 0.60 and 0.99 levels for liver, spleen, red marrow, total body, and other organ systems. Median results were: 27, 17, and 2.7 rad/mCi of 90Y-cT84.66 for liver, spleen, and red marrow, respectively. Because of decreases in platelets and white cells as the amount of 90Y was increased, dose-limiting toxicity was found at 22 mCi/m2. We conclude that patient biodistributions were consistent over time to 14 days so as to allow absorbed dose estimation in a radioimmunotherapy trial involving the cT84.66 anti-CEA antibody.
authors.affiliation: Division of Information Sciences, City of Hope National Medical Center, Duarte, California 91010-3000, USA.
authors.forename: K G
authors.initials: KG
authors.lastname: Clarke
authors.forename: T L
authors.initials: TL
authors.lastname: Odom-Maryon
authors.forename: L E
authors.initials: LE
authors.lastname: Williams
authors.forename: A
authors.initials: A
authors.lastname: Liu
authors.forename: G
authors.initials: G
authors.lastname: Lopatin
authors.forename: J
authors.initials: J
authors.lastname: Chou
authors.forename: G M
authors.initials: GM
authors.lastname: Farino
authors.forename: A A
authors.initials: AA
authors.lastname: Raubitschek
authors.forename: J Y
authors.initials: JY
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*; D011880:Radiotherapy Planning, Computer-Assisted; D015203:Reproducibility of Results; D013997:Time Factors; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000097:blood / Q000627:therapeutic use* / Q000652:urine
chemical_list: D007205:Indium Radioisotopes; D015021:Yttrium Radioisotopes