Tumour radioimmunolocalization in nude mice by use of antiplacental alkaline phosphatase monoclonal antibodies.
Three monoclonal antibodies and their Fab and Fab'2 fragments with specificity against human placental alkaline phosphatase (PLAP) were evaluated for tumour immunolocalization of human PLAP-producing Hela Hep 2 tumours in nude mice. The antibodies and their fragments were labelled with 125I and injected intraperitoneally in mice with developing Hep 2 tumours. The animals were followed individually for 14 days with repetitive computerized gamma-camera recordings, which enable quantitation of several crucial parameters, i.e. the time-dependent antibody uptake in the tumours, decrease in background activity and tumour/background ratio. Excellent radioimmunolocalization was obtained with both the intact PLAP-specific immunoglobulins and their fragments but not with the nonspecific antibodies. No background subtraction had to be used. As much as 15% of the initially injected dose could be visualized in the tumours and for the uncleaved mab up to 80% of the radioactivity in the animals was retained in the tumours after 14 days, a considerably longer observation time than usually reported in such tumour xenograft models. The Fab and Fab'2 fragments were found to be excreted fast with less than 5% of the injected dose remaining in the animals after 48 h, but still with positive specific localization to the tumours after an initial high uptake in the kidneys. The results are encouraging and indicate significant potentials of the PLAP-antiPLAP mab system for immunolocalization studies in patients.
Stigbrand
T
T
Department of Physiological Chemistry, University of Umeå, Sweden.
Hietala
S O
SO
Johansson
B
B
Makiya
R
R
Riklund
K
K
Ekelund
L
L
D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000276:immunology; D000469:Alkaline Phosphatase / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D014408:Biomarkers, Tumor / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007128:Immunoglobulin Fragments; D007527:Isoenzymes / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010920:Placenta / Q000276:immunology; D011877:Radionuclide Imaging; D013997:Time Factors
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007128:Immunoglobulin Fragments; D007527:Isoenzymes; D000469:Alkaline Phosphatase