Combinations of nonlabeled, 125I-labeled, and anti-idiotypic antiplacental alkaline phosphatase monoclonal antibodies at experimental radioimmunotargeting.
OBJECTIVE
Placental alkaline phosphatase (PLAP) is a membrane-bound oncofetal antigen that can be used for radioimmunotargeting. Preinjection of nonlabeled monoclonal anti-PLAP antibody (H7) and postinjection of monoclonal anti-idiotypic anti-PLAP antibody (alpha H7) were used in order to improve the localization efficacy of 125I-labeled H7.


METHODS
A human cervix adenocarcinoma cell line (HcLa Hep 2) was inoculated subcutaneously in 24 nude mice. Repeated quantitative radioimmunoscintigraphic recordings were performed on 27 occasions in each of the 24 mice during the observation period which lasted for nearly 3 months. The tumor and nontumor doses were calculated according to the Medical International Radiation Dose Committee formula on the basis of the scintigraphic data.


RESULTS
All tumors were clearly visualized as early as one day after injection of 125I-labeled H7. The remaining radioactivity was exclusively located in the tumors at days 30-81. As much as 12-16% of the injected dose/g accumulated in the tumors during the first 2 days after injection, and remained stable at this high level for approximately 10 days in all investigated groups. Radioactivity in the whole body was rapidly eliminated during the same time period. The highest tumor/nontumor dose ratio was obtained after a single injection of 125I-labeled H7.


CONCLUSIONS
Neither a preinjection of nonlabeled H7 nor a postinjection of alpha H7 nor a combination of both strategies resulted in improved tumor/nontumor dose ratios compared to a single injection of labeled H7. The monoclonal antibody H7 has a rapid and high uptake, combined with a prolonged retention time in the tumors. The kinetic properties of H7 are different from antibodies targeting intracellular tumor antigens.
Rossi Norrlund
R
R
Department of Diagnostic Radiology, University Hospital, Umeå, Sweden.
Holback
D
D
Johansson
L
L
Hietala
S O
SO
Ahlström
K R
KR
D000230:Adenocarcinoma / Q000000981:diagnostic imaging*; D000469:Alkaline Phosphatase / Q000276:immunology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010920:Placenta / Q000201:enzymology; D011829:Radiation Dosage; D016719:Radioimmunodetection; D019275:Radiopharmaceuticals; D012983:Soft Tissue Neoplasms / Q000000981:diagnostic imaging*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D000469:Alkaline Phosphatase