Immunoconjugate stability in vivo measured by label release from 125I or 99mTc-antibody coated cells kept in intraperitoneal diffusion chambers in mice.
The present work demonstrates how intraperitoneal (i.p.) diffusion chambers (DC) can be used to investigate the in vivo stability of the bond between an antibody and its radioactive label. A monoclonal antibody (MoAb) was labelled with 125I or 99mTc. The 125I-labelled preparation showed high stability in vitro, since little radioactivity eluted from incubated DC containing 125I-MoAb bound to specific, fixed target cells. Similarly, when we evaluated the 125I-MoAb in vivo by using the i.p. DC the stability was intact. The 99mTc-MoAb was also stable in vitro, with only about 10% of the radioactivity lost after 48 h. However, when tested in vivo, about 50% of the 99mTc label was lost after 1 day, increasing to 60% after 2 days. Hence, by carrying out preclinical in vivo stability testing with i.p. DC method we discovered that an immunoconjugate with high stability as tested in vitro, in fact was unstable in vivo and probably unsuited for clinical use.
Fjeld
J
J
Department of Clinical Chemistry, Rikehospitalet, Oslo, Norway.
Brorson
B
B
Martinussen
G K
GK
Benestad
H
H
Nustad
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D015194:Diffusion Chambers, Culture; D004355:Drug Stability; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling; D008223:Lymphoma / Q000000981:diagnostic imaging / Q000532:radiotherapy; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D011851:Radioactivity; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D013667:Technetium / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D013667:Technetium