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

Abstract

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 ₂‐W Fast Spin echo and T ₂*‐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 ₂‐W and the T ₂*‐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 ₂‐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 ₂*‐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