Quantitative [Fe]MRI of PSMA-targeted SPIONs specifically discriminates among prostate tumor cell types based on their PSMA expression levels

Abstract

We report the development, experimental verification, and application of a general theory called [Fe]MRI (pronounced fem-ree) for the non-invasive, quantitative molecular magnetic resonance imaging (MRI) of added magnetic nanoparticles or other magnetic contrast agents in biological tissues and other sites. [Fe]MRI can easily be implemented on any MRI instrument, requiring only measurements of the background nuclear magnetic relaxation times (T₁, T₂) of the tissue of interest, injection of the magnetic particles, and the subsequent acquisition of a pair of T₁-weighted and T₂-weighted images. These images, converted into contrast images, are subtracted to yield a contrast difference image proportional to the absolute nanoparticle, iron concentration, ([Fe]) image. [Fe]MRI was validated with the samples of superparamagnetic iron oxide nanoparticles (SPIONs) both in agarose gels and bound to human prostate tumor cells. The [Fe]MRI measurement of the binding of anti-prostate specific membrane antigen (PSMA) conjugated SPIONs to PSMA-positive LNCaP and PSMA-negative DU145 cells in vitro allowed a facile discrimination among prostate tumor cell types based on their PSMA expression level. The low [Fe] detection limit of ~2 μM for SPIONs allows sensitive MRI of added iron at concentrations considerably below the US Food and Drug Administration’s human iron dosage guidelines (<90 μM, 5 mg/kg).

Keywords:

• contrast difference
• RT-PCR
• flow cytometry

Acknowledgments

This research was supported in part by a National Cancer Institute grant to LOS (NIH 5 R01 CA123194). It is a pleasure to thank New Mexico Resonance for the use of their MRI instrumentation, and R Serda, M Bisoffi, M Ji, RM Taylor, S Altobelli, D Kuethe, N Adolphi, and L Sanfratello for excellent technical assistance.

Disclosure

The author reports no conflicts of interest in this work.