Our approach towards developing a specific tumour-targeted MRI contrast agent for the brain.
This review presents various aspects of the technological development, and their assessment in the design of a contrast agent for MRI, tailored to visualise tumours in the brain. First, it was demonstrated that magnetite as a contrast agent exhibited a much stronger relaxivity than gadolinium. The prepared magnetite particles bound to dextran, were also shown to be of appropriate size by electron microscopy. After their intravenous injection into rats with blood-brain barrier disruption, the lesion was strongly enhanced by T2-shortening. Furthermore, monoclonal antibodies directed against small cell lung carcinoma, proved to be able to penetrate into tumours, which had been raised by implantation of the small cell lung carcinoma cells into the brains of nude rats. As to the essential step, it was demonstrated in vitro that magnetite particles coupled to monoclonal antibodies by the biotin-streptavidin binding, could be bound to the target cells of the antibody, changing the relaxation rates of the latter. Finally it could be shown in vitro that an alternative approach, using lymphocytes to be targeted to tumour cells, also proved feasible, in that these lymphocytes could be labelled with magnetite that had been incorporated into liposomes. Further developments will be the in vivo assessment of the acquired progress in experimental animals, before clinical application is warranted.
Go
K G
KG
Department of Neurosurgery, University Hospital Groningen, Netherlands.
Bulte
J W
JW
de Ley
L
L
The
T H
TH
Kamman
R L
RL
Hulstaert
C E
CE
Blaauw
E H
EH
Ma
L D
LD
D000818:Animals; D000911:Antibodies, Monoclonal; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000175:diagnosis*; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D006801:Humans; D007501:Iron; D008214:Lymphocytes; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010087:Oxides; D051381:Rats; D011923:Rats, Nude; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D003287:Contrast Media; D003911:Dextrans; D010087:Oxides; D007501:Iron; D052203:Ferrosoferric Oxide