239 Targeted Magnetic Nanoparticles for MRI Detection of Prostate Cancer

Thursday, November 5, 2009: 10:00 AM
Hereford (Camino Real Hotel)
Natalie L. Adolphi, Ph.D. , Biochemistry and Molecular Biology, University of New Mexico, Albuquerque, NM
Robert M. Taylor , Biochemistry and Molecular Biology, University of New Mexico, Albuquerque, NM
Marco Bisoffi , Biochemistry and Molecular Biology, University of New Mexico, Albuquerque, NM
Laurel O. Sillerud , Biochemistry and Molecular Biology, University of New Mexico, Albuquerque, NM
Lori Sanfratello , New Mexico Resonance, Albuquerque, NM
Shin Utsuzawa , New Mexico Resonance, Albuquerque, NM
Dean O. Kuethe , New Mexico Resonance, Albuquerque, NM
Stephen A. Altobelli , New Mexico Resonance, Albuquerque, NM
We report progress toward the development of a targeted contrast agent for specific MRI detection of human prostate cancer. Here we investigate antibodies against prostate specific membrane antigen (PSMA) conjugated to two different types (Dynabeads and MACS) of commercial superparamagnetic iron oxide nanoparticles (SPIONs). Biotinylated anti-PSMA monoclonal antibodies (3C6 or J591) were conjugated to the streptavidin-labeled SPIONs and used in an MRI study of two of the cell lines: LNCaP cells (PSMA-positive) and DU-145 cells (control). After labeling with anti-PSMA-conjugated SPIONs, the cells, suspended in agarose gel, were imaged using several different MRI methods. For the LNCaP cells, the presence of the Dynabead-conjugated antibodies resulted in significant dark contrast in spin-echo (T2-weighted) and gradient-echo (T2*-weighted) images, as expected. The presence of the MACS-conjugated antibodies resulted in strong bright contrast in T1-weighted images, which is surprising, as bright contrast is typically not observed from SPION contrast agents. In the case of the DU-145 cells, comparitively weak contrast was observed using either agent due to the lack of specific binding. The observed contrast is explained based on the measured relaxivities (r1 and r2) of the SPIONs. Images of xenograft tumor-bearing mice, injected with MACS-conjugated antibodies, also demonstrate that bright contrast can be achieved in vivo for relevant intra-tumoral SPION concentrations.