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Experimental radioimmunotargeting combining nonlabeled, iodine‐125‐labeled, and anti‐idiotypic anticytokeratin monoclonal antibodies
Author(s) -
Norrlund Rauni Rossi,
Ullén Anders,
Sandström Per,
Holback Daniel,
Johansson Lennart,
Stigbrand Torgny,
Hietala SvenOla,
Åhlström Katrine Riklund
Publication year - 1997
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19971215)80:12+<2689::aid-cncr47>3.0.co;2-5
Subject(s) - monoclonal antibody , in vivo , medicine , antibody , pharmacology , pathology , immunology , biology , microbiology and biotechnology
BACKGROUND Preinjection of a nonlabeled tumor targeting anticytokeratin monoclonal antibody (TS1) and postinjection of an anti‐idiotypic anticytokeratin monoclonal antibody (αTS1) were evaluated separately and in combination to investigate their effects on the accumulation of iodine‐125 ( 125 I)‐labeled TS1 in experimental radioimmunotargeting. TS1 targets deposited extracellular cytokeratin 8 from necrotic tumor cells. METHODS Nude mice were inoculated with HeLa Hep 2 cells. Four different groups were followed with 504 repetitive quantitative radioimmunoscintigraphic recordings during a 78‐day observation period. The absorbed doses were calculated according to criteria of the Medical International Radiation Dose Committee. RESULTS As much as 2% of the injected dose (ID) of 125 I‐labeled TS1 accumulated in the tumor, and the peak tumor uptake was recorded as late as Day 30 after the injection of 125 I‐labeled TS1. Anti‐TS1 caused a rapid decrease in the whole body activity. The highest tumor‐to‐nontumor activity ratios were obtained when a preinjection of nonlabeled TS1 was combined with a postinjection of αTS1. The mean absorbed dose in tumor per unit activity administered was 0.44 gray/megabecquerel (Gy/MBq) and in nontumor tissues 0.15 Gy/MBq after a single injection of 125 I‐TS1. The efficacy was 0.34 Gy/MBq in tumor and 0.1 Gy/MBq in nontumor tissues after a combination of preinjection of nonlabeled TS1 and postinjection of nonlabeled αTS1. This indicates a 20% increase in tumor doses compared with a single injection of labeled TS1. CONCLUSIONS This study confirms an extensive accumulation of TS1 in the tumor, with peak values as late as 30 days after injection of labeled TS1. Furthermore, both preinjection of nonlabeled TS1 and postinjection of αTS1 can improve radioimmunotargeting. Cancer 1997; 80:2689‐98. © 1997 American Cancer Society.