Passage of DMP across a disrupted BBB in the context of antibody-mediated MR imaging of brain metastases.
To study the possible application of monoclonal antibody/dextran-magnetite conjugates in specific MR imaging of brain metastases, both components of these conjugates were tested for their ability to penetrate the endothelium during conditions of local blood-brain barrier (BBB) impairment. The passage of dextran-magnetite particles (DMP) across a disrupted blood-brain barrier was studied in a freezing lesion model using electron microscopy (EM) and MR imaging. One hour after i.v. injection, focal accumulation of DMP in capillary endothelial cells within the freezing lesion was shown by EM. In parallel with this, MR imaging indicated a strong contrast enhancement in the lesion. EM observations showed that the particles were still present in the endothelial cells four and eight hours after injection. The passage of an anti-small cell lung cancer (SCLC) monoclonal antibody across the endothelium of intracerebrally xenografted human SCLC was studied using immunohistological techniques. It was found that passage across endothelial cell occurred in the tumor within four hours after injection.
Bulte
J W
JW
Department of Clinical Immunology, University of Groningen, The Netherlands.
de Jonge
M W
MW
de Leij
L
L
The
T H
TH
Kamman
R L
RL
Blaauw
B
B
Zuiderveen
F
F
Go
K G
KG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D018288:Carcinoma, Small Cell / Q000378:metabolism; D003911:Dextrans / Q000493:pharmacokinetics*; D008175:Lung Neoplasms / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D011923:Rats, Nude; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D003911:Dextrans