Intrapatient consistency of imaging biodistributions and their applicationto predicting therapeutic doses in a phase I clinical study of Y-90-based radioimmunotherapy

Intrapatient variation in the biodistribution of the chimeric monoclonal an tibody cT84.66 was assessed in 19 patients having a variety of carcinoembry onic antigen (CEA) positive tumors. The two studies, including whole-body i maging and blood and urine specimen collections, were conducted within 14 d ays of each other using In-111-cT84.66 at a fixed total protein dose of 5 m g per patient per study. An initial pretherapy infusion of In-111-cT84.66 w as administered followed by a therapy coinfusion of In-111-ct84.66 and Y-90 -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 rad iotherapeutic agent. For the two In-111-cT84.66 biodistributions, all data were modeled with a R-2 value of between 0.72 and 1.00 with the exception o f the urine data taken during therapy. This was due to the need of diethyle netriaminepentaacetic acid during the therapy phase because of the possibil ity that yttrium might escape from the chelator attached to the antibody. W ith the assurance that the biodistributions were reproducible, we were able to estimate the Y-90-cT84.66 absorbed doses on a per-patient basis. Concor dance coefficients showing the agreement between the imaging and therapy ph ase 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 Y-90-cT84.66 for liver, spleen, and red marrow, resp ectively. Because of decreases in platelets and white cells as the amount o f Y-90 was increased, dose-limiting toxicity was found at 22 mCi/m(2). We c onclude that patient biodistributions were consistent over time to 14 days so as to allow absorbed dose estimation in a radioimmunotherapy trial invol ving the cT84.66 anti-CEA antibody. (C) 1999 American Association of Physic ists in Medicine. [S0094-2405(99)02005-2].