The Study Of Extracorporeal Immunoadsorption In Radioimmunotherapy

Extracorporeal adsorption (ECAT) is a novel strategy to reduce activities in the whole body (WB), blood, and radiosensitive organs by removing the excess of radiolabeled and biotinylated monoclonal antibodies (MAbs) from blood so that tumor/normal tissue ratio (T/N) could be improved. By increasing T/N ratio, higher amounts of radiolabeled MAbs might be administered, making it possible to treat disseminated carcinomas. Paper 1. To determine whether ECAT also could be used to reduce activities after intraperitoneal administration (~111In-HMFGl-biotin) in rats and to compare the pharmacokinetics +/-attached biotin. When ECAT was employed, the WB and blood radioactivities were reduced by 35-40% (P < 0.05) and 75-86% (P < 0.01), respectively. After the completion of ECAT, the activity uptake in organs was significantly decreased. Paper 2. The optimal time for performing ECAT must be decided prior to ECAT. Knowledge of the blood pharmacokinetics of MAbs is crucially important for it. The purpose of this study was to investigate if pharmacokinetics from one radiolabeled MAbs in rats can be generalized to other MAbs labeled with the same chelator ("1033") and radionuclide (~111In) to avoid time-consuming pharmacokinetic studies for each individual MAb used. The pharmacokinetics of three chimeric/humanized MAbs (rituximab, trastuzumab, BR96) were evaluated. No statistical difference was detected between blood pharmacokinetics. The WB activity clearance and the organ uptake for three groups were very similar. A further MAb (hMN14) which was labeled to another chelator (DOTA-biotin), was found to have a faster blood pharmacokinetics, WB activity clearance, and higher liver activity uptake. The pharmacokinetics could be predicted irrespective of the MAb chosen prior to ECAT when labeled with the same tri-functional chelator "1033" and ~111In. A small tumor burden didnot change the biokinetics.