Molecular MR Imaging of Prostate Cancer by Specified Iron Oxide Nanoparticles With PSMA-11 Peptides: A Preclinical Study.

Background: Prostate-specific membrane antigen (PSMA) can provide a prostate cancer (PCa) detection approach in positron emission tomography (PET) using Food and Drug Administration (FDA)-approved PSMA-11 peptide. There are some studies evaluated magnetic-nanoprobes for PSMA detection by MRI, using non-FDA-approved ligands including antibodies or peptides, which are not as specific as PSMA-11.

Purpose: To assess targeted iron oxide nanoparticles (IONPs) by PSMA-11 peptides as a potential specific nano-molecular probes to investigate a PSMA PCa-xenograft model by MRI.

Study Type: Prospective.

Animal Model: Twenty male C57BL6 nude mice induced subcutaneously PSMA LNCaP cell line tumor.

Field Strength/sequence: 1.5 T, T-W Fast Spin echo and T*-W Gradient echo.

Assessment: Coated IONPs with Carboxymethylated-dextran (DNPs) and with bovine serum albumin (BNPs), as well as, targeted DNPs with PSMA-11-HYNIC peptide (TDNPs) and targeted BNPs with PSMA-11-HBED peptide (TBNPs) were injected intravenously with dose 2.8 mg Fe/kg. Coronal T-W and the T*-W images were obtained before and 4 hours and 6 hours post-injection. Signal intensity (SI) and relative signal enhancement (RSE) were computed in two- and three-dimensional analyses. Histological analysis of tumors was evaluated, and the Fe distribution within the body based on atomic absorption spectroscopy was calculated.

Statistical Tests: One-way ANOVA followed by Tukey's multiple comparison test, Paired-samples T-test, P < 0.05 was considered significant.

Results: A reduction in T-W SI was achieved as 22 ± 7%, 59 ± 3%, 65 ± 5%, and 78 ± 3% respectively for BNPs, TBNPs, DNPs, and TDNPs 6 hours post-injection. The most difference between targeted and non-targeted groups was observed at 6 hours for PSMA-11-HBED, and at 4 hours for PSMA-11-HYNIC. RSE indicated 88.6 ± 3.1% and 80.7 ± 3.2% enhanced contrast between tumor and muscle region for TBNPs and TDNPs on T*-W images.

Conclusions: Both TBNPs and TDNPs are promising novel nano-molecular probes for PSMA PCa tumor detection. The injection dose of non-targeted IONPs can be reduced by using targeted nanoprobes three times for BNPs and two times for DNPs.

Evidence Level: 1 TECHNICAL EFFICACY: Stage 1.