Biokinetics of radiolabeled monoclonal antibodies in heterotransplanted nude rats: evaluation of corrected specific tissue uptake.
A tumor model is presented to study the biokinetics and localization of radiolabeled monoclonal antibodies (MAb) in the nude rat (Rowett RNu/RNu) heterotransplanted with human melanoma metastases. The nude rat is larger, less sensitive, and lives longer than the nude mouse. It is, therefore, well suited for in vivo studies of tumor localization with radiolabeled monoclonal antibodies. The tumor-to-host weight ratio was closer to the human situation for the nude rat than for the mouse, and quantitative imaging could be performed with a parallel hole collimator. We followed the antibody biokinetics for as long as 8 days, with repeated blood sampling and imaging. Specific uptake of MAb was higher in tumor tissue than in all other tissues except blood. Initial high uptake was also recorded in the bone marrow. The lymph glands showed a slow uptake of specific and control antibody. A simple in vitro correction procedure is described to calculate the corrected specific tissue uptake (STUcorr) that takes the blood activity into account. Thus it was shown that 80% of the tissue uptake in the dissected liver at 30 hr was due to labeled antibodies circulating in the blood. The specific tissue uptake ratio of antibodies 96.5 and OKT3 (nonspecific control) was unity for all other organs except for tumor tissue, where the ratio was greater than two and even higher when correction for blood content of labeled antibody was made.
Ingvar
C
C
Department of Surgery, Lund University, Sweden.
Norrgren
K
K
Strand
S E
SE
Brodin
T
T
Jönsson
P E
PE
Sjögren
H O
HO
D000818:Animals; D000911:Antibodies, Monoclonal; D001835:Body Weight; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D011923:Rats, Nude; D012039:Regional Blood Flow; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes