MRI Assessment of Prostate-Specific Membrane Antigen (PSMA) Targeting by a PSMA-Targeted Magnetic Nanoparticle: Potential for Image-Guided Therapy

Mol Pharm. 2019 May 6;16(5):2060-2068. doi: 10.1021/acs.molpharmaceut.9b00036. Epub 2019 Apr 10.

Abstract

Magnetic nanoparticle (MNP)-induced hyperthermia is currently being evaluated for localized prostate cancer. We evaluated the feasibility of tumor-selective delivery of prostate-specific membrane antigen (PSMA)-targeted MNPs in a murine model with high-resolution magnetic resonance imaging (MRI) after intravenous administration of MNPs at a concentration necessary for hyperthermia. A PSMA-targeted MNP was synthesized and evaluated using T2-weighted MRI, after intravenous administration of 50 mg/kg of the MNP. Significant contrast enhancement ( P < 0.0002, n = 5) was observed in PSMA(+) tumors compared to PSMA(-) tumors 24 h and 48 h after contrast agent administration. Mice were also imaged with near-infrared fluorescence imaging, to validate the MRI results. Two-photon microscopy revealed higher vascular density at the tumor periphery, which resulted in higher peripheral accumulation of PSMA-targeted MNPs. These results suggest that the delivery of PSMA-targeted MNPs to PSMA(+) tumors is both actively targeted and passively mediated.

Keywords: MNP; magnetic hyperthermia therapy; magnetic resonance imaging; optical imaging; prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Surface / chemistry*
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism*
  • Cohort Studies
  • Contrast Media / chemistry*
  • Drug Delivery Systems
  • Feasibility Studies
  • Glutamate Carboxypeptidase II / chemistry*
  • Glutamate Carboxypeptidase II / genetics
  • Glutamate Carboxypeptidase II / metabolism*
  • Humans
  • Hyperthermia, Induced
  • Magnetic Resonance Imaging*
  • Magnetite Nanoparticles / chemistry*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Optical Imaging
  • PC-3 Cells
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / therapy*
  • Transfection
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, Surface
  • Contrast Media
  • Magnetite Nanoparticles
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II