Two-step in vivo tumor targeting by biotin-conjugated antibodies and superparamagnetic nanoparticles assessed by magnetic resonance imaging at 1.5 T.
OBJECTIVE
The purpose of this study was to assess two-step in vivo tumor targeting by specific biotin-conjugated antibodies and ultrasmall superparamagnetic iron oxide (USPIO)-anti-biotin nanoparticles as contrast agents for magnetic resonance imaging (MRI) at 1.5 T.


METHODS
D430B human lymphoma cells, expressing the CD70 surface antigen, were injected either s.c. or i.v. to induce pseudo-metastases in NOD/SCID mice. Thirty micrograms of biotin-conjugated monoclonal anti-CD70 was injected i.v., followed 4 h later by 8 micromol Fe/Kg USPIO-anti-biotin. After 24 h, MRI was performed on T2* and b-FFE sequences. Signal intensity (SI) was calculated before and after USPIO-anti-biotin administration.


RESULTS
Subcutaneous xenografts showed a dishomogeneous 30% decrease in SI on T2* with anti-CD70 + USPIO-anti-biotin treatment. Pseudo-metastatic xenografts showed a slight reduction in SI on T2*, but a 60% decrease in SI on b-FFE-weighted sequences. Prussian blue staining confirmed the presence of iron nanoparticles in the excised tumors.


CONCLUSIONS
MRI at 1.5 T can detect tumors by a two-step in vivo biotin-based protocol, which may allow the targeting of any cell surface antigen.
Baio
Gabriella
G
Department of Diagnostic Imaging, IST, National Cancer Institute, Largo Rosanna Benzi 10, 16132, Genoa, Italy.
Fabbi
Marina
M
Salvi
Sandra
S
de Totero
Daniela
D
Truini
Mauro
M
Ferrini
Silvano
S
Neumaier
Carlo Emanuele
CE
D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology*; D001710:Biotin / Q000378:metabolism*; D053282:CD27 Ligand / Q000378:metabolism; D045744:Cell Line, Tumor; D003911:Dextrans / Q000378:metabolism*; D052203:Ferrosoferric Oxide / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology*; D008223:Lymphoma / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D053758:Nanoparticles / Q000737:chemistry*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D013194:Staining and Labeling; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D053282:CD27 Ligand; C505771:CD70 protein, human; D003911:Dextrans; D018796:Immunoconjugates; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10; D001710:Biotin; D052203:Ferrosoferric Oxide