Relationship between ZCE 025 blood clearance and liver accumulation in patients with colorectal cancer.
Clinical interest in radiolabelled monoclonal antibodies (mAbs) derives from their ability to target tissues and deliver radioisotopes thereto. Diagnostic and therapeutic trials suggest that the potential of mAbs would be optimized with better understanding of factors which influence blood clearance. This study sought to advance that understanding. Nine colon cancer patients were injected with 20 mg 111In radiolabelled ZCE 025 mAb, then laser-positioned and imaged daily for one week via nuclear medicine views. Laser-positioned CT images were also obtained, enabling image registration. Blood samples were taken at 30, 60, and 90 min and at every imaging time point. Sample activity was plotted to estimate the elimination half-life (t1/2 beta). Liver radiation dose was calculated from the images and evaluated for total organ (mCi-h) and region of interest (microCi-h/g). Laboratory values and patients' physical parameters were also studied to determine their impact on liver uptake and mAb blood clearance. Liver radiation dose, as measured in this study, correlated with terminal half-life of the mAb in blood; patients' liver enzymes and physical parameters did not. Radioactivity in a 48-h or 72-h blood sample correlates with t1/2 beta and liver radiation dose, suggesting that a single 72-h sample can predict both.
Slater
J B
JB
Department of Radiology, Loma Linda University Medical Center, CA 92354, USA.
Slater
J M
JM
Gridley
D S
DS
Kirk
G A
GA
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000493:pharmacokinetics*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002277:Carcinoma / Q000097:blood / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007205:Indium Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007205:Indium Radioisotopes; C081679:monoclonal antibody ZCE 025