PURPOSE: Pharmacokinetics and dosimetry of hMN-14 x m734 bispecific monoclonal antibody (BsMAb) and (131)I-labeled di-diethylenetriaminepentaacetic acid-indium ((131)I-hapten) were studied to optimize pretargeted radioimmunotherapy. EXPERIMENTAL DESIGN: Thirty-five patients with carcinoembryonic antigen-expressing tumors were included. In a first group of 12 patients, (131)I-trace-labeled BsMAb doses were escalated from 10 to 100 mg/m(2), and 3.7 GBq of (131)I-hapten were administered 7 days later. In a second group, 12 patients received 75 mg/m(2) BsMAb and 2.6-4.2 GBq of (131)I-hapten 5 days later. The BsMAb dose was then reduced to 40 mg/m(2), and 10 patients received 1.9-5.5 GBq of (131)I-hapten. Blood samples were collected. Biodistribution was monitored by quantitative scintigraphy. RESULTS: Directly labeled BsMAb pharmacokinetics was described by two exponentials: half-lives were 8.1 h (2.0-18.1 h) and 48.2 h (22.8-79.4 h); blood clearance was 123 ml/h (64-195 ml/h). With a 7-day interval, 10 or 30 mg/m(2) BsMAb resulted in fast elimination and very low tumor uptake of hapten, whereas 50 or 100 mg/m(2) resulted in favorable tumor accretion. With 75 mg/m(2) BsMAb and a 5-day interval, hapten clearance was 152 ml/h (81-298 ml/h). Calculated radiation dose to tumor was 3.9 Gy/GBq (0.4-22.4 Gy/GBq) for the hapten, compared with 2.0 Gy/GBq (0.3-3.8 Gy/GBq) for the BsMAb, but hematological toxicity prevented dose escalation. Reduction of the BsMAb dose to 40 mg/m(2) accelerated hapten clearance to 492 ml/h (113-2544 ml/h) and reduced hematological toxicity without compromising tumor uptake [5.2 Gy/GBq (0.5-12.6 Gy/GBq)]. CONCLUSIONS: Optimized BsMAb doses and time interval will allow for the administration of higher, tumoricidal, activity doses.
PURPOSE: Pharmacokinetics and dosimetry of hMN-14 x m734 bispecific monoclonal antibody (BsMAb) and (131)I-labeled di-diethylenetriaminepentaacetic acid-indium ((131)I-hapten) were studied to optimize pretargeted radioimmunotherapy. EXPERIMENTAL DESIGN: Thirty-five patients with carcinoembryonic antigen-expressing tumors were included. In a first group of 12 patients, (131)I-trace-labeled BsMAb doses were escalated from 10 to 100 mg/m(2), and 3.7 GBq of (131)I-hapten were administered 7 days later. In a second group, 12 patients received 75 mg/m(2) BsMAb and 2.6-4.2 GBq of (131)I-hapten 5 days later. The BsMAb dose was then reduced to 40 mg/m(2), and 10 patients received 1.9-5.5 GBq of (131)I-hapten. Blood samples were collected. Biodistribution was monitored by quantitative scintigraphy. RESULTS: Directly labeled BsMAb pharmacokinetics was described by two exponentials: half-lives were 8.1 h (2.0-18.1 h) and 48.2 h (22.8-79.4 h); blood clearance was 123 ml/h (64-195 ml/h). With a 7-day interval, 10 or 30 mg/m(2) BsMAb resulted in fast elimination and very low tumor uptake of hapten, whereas 50 or 100 mg/m(2) resulted in favorable tumor accretion. With 75 mg/m(2) BsMAb and a 5-day interval, hapten clearance was 152 ml/h (81-298 ml/h). Calculated radiation dose to tumor was 3.9 Gy/GBq (0.4-22.4 Gy/GBq) for the hapten, compared with 2.0 Gy/GBq (0.3-3.8 Gy/GBq) for the BsMAb, but hematological toxicity prevented dose escalation. Reduction of the BsMAb dose to 40 mg/m(2) accelerated hapten clearance to 492 ml/h (113-2544 ml/h) and reduced hematological toxicity without compromising tumor uptake [5.2 Gy/GBq (0.5-12.6 Gy/GBq)]. CONCLUSIONS: Optimized BsMAb doses and time interval will allow for the administration of higher, tumoricidal, activity doses.
Authors: Eric Mirallié; Catherine Saï-Maurel; Alain Faivre-Chauvet; Nicolas Regenet; Chien-Hsing Chang; David M Goldenberg; Jean-François Chatal; Jacques Barbet; Philippe Thedrez Journal: Eur J Nucl Med Mol Imaging Date: 2005-04-30 Impact factor: 9.236