Effect of blood-brain barrier disruption on intact and fragmented monoclonal antibody localization in intracerebral lung carcinoma xenografts.
These studies highlight several factors that affect monoclonal antibody (Mab) localization to a tumor in the brain, including tumor permeability, nonspecific and specific binding, plasma half-life, radiolabeled antibody stability and the blood-brain barrier.


METHODS
A pancarcinoma Mab [L6 IgG, F(ab')2 and Fab] and an irrelevant isotype-matched antibody [P1.17 IgG and F(ab')2] were given with and without osmotic blood-brain barrier disruption in a LX-1 human small-cell lung carcinoma intracerebral xenograft model.


RESULTS
Intracerebral tumor size and permeability to antibody increased with the selection of 10, 14 or 17 days postinoculation when antibody was administered. Barrier disruption increased the delivery, particularly at earlier time points, which was dependent on antibody-specific and nonspecific binding and tumor permeability. Dehalogenation and/or antibody binding stability also appeared to affect the percent delivery.


CONCLUSIONS
These studies demonstrate important variables that should be considered when clinical trials are designed or Mab delivery and localization in intracerebral tumor models are evaluated.
Oregon Health Sciences University, Portland.
E A
EA
Neuwelt
P A
PA
Barnett
K E
KE
Hellström
I
I
Hellström
C I
CI
McCormick
F L
FL
Ramsey
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging* / Q000628:therapy*; D008175:Lung Neoplasms / Q000473:pathology; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D051381:Rats; D011923:Rats, Nude; D014183:Transplantation, Heterologous