Targeting prostate cancer with Clostridium perfringens enterotoxin functionalized nanoparticles co-encapsulating imaging cargo enhances magnetic resonance imaging specificity.

Magnetic resonance is a key imaging tool for the detection of prostate cancer; however, better tools focusing on cancer specificity are required to distinguish benign from cancerous regions. We found higher expression of claudin-3 (CLDN-3) and -4 (CLDN-4) in higher grade than lower-grade human prostate cancer biopsies (n = 174), leading to the design of functionalized nanoparticles (NPs) with a non-toxic truncated version of the natural ligand Clostridium perfringens enterotoxin (C-CPE) that has a strong binding affinity to Cldn-3 and Cldn-4 receptors. We developed a first-of-its-type, C-CPE-NP-based MRI detection tool in a prostate tumor-bearing mouse model. NPs with an average diameter of 152.9 ±â€¯15.7 nm (RS1) had a 2-fold enhancement of tumor specificity compared to larger (421.2 ±â€¯33.8 nm) NPs (RS4). There was a 1.8-fold (P < 0.01) and 1.6-fold (P < 0.01) upregulation of the tumor-to-liver signal intensities of C-RS1 and C-RS4 (functionalized NPs) compared to controls, respectively. Also, tumor specificity was 3.1-fold higher (P < 0.001) when comparing C-RS1 to C-RS4. This detection tool improved tumor localization of contrast-enhanced MRI, supporting potential clinical applicability.

Feasibility of diffusion weighting with a local inside-out nonlinear gradient coil for prostate MRI.

PURPOSE: Prostate cancer remains the second leading cancer killer of men, yet it is also a disease with a high rate of overtreatment. Diffusion-weighted imaging (DWI) has shown promise as a reliable, grade-sensitive imaging method, but it is limited by low image quality. Currently, DWI quality image is directly related to low gradient amplitudes, since weak gradients must be compensated with long echo times. METHODS: We propose a new type of MRI accessory, an "inside-out" and nonlinear gradient, whose sole purpose is to deliver diffusion encoding to a region of interest. Performance was simulated in OPERA and the resulting fields were used to simulate DWI with two-compartment and kurtosis models. Experiments with a nonlinear head gradient prove the accuracy of DWI and apparent diffusion coefficient (ADC) maps encoded with nonlinear gradients. RESULTS: Simulations validated thermal and mechanical safety while showing a 5- to 10-fold increase in gradient strength over prostate. With these strengths, lesion contrast to noise ratio in ADC maps approximately doubled for a range of anatomical positions. Proof-of-principle experiments show that spatially varying b-values can be corrected for accurate DWI and ADC. CONCLUSIONS: Dedicated nonlinear diffusion encoding hardware could improve prostate DWI.

iDQC anisotropy map imaging for tumor tissue characterization in vivo.

Intermolecular double quantum coherences (iDQCs), signals that result from simultaneous transitions of two or more separated spins, are known to produce images that are highly sensitive to subvoxel structure, particularly local anisotropy. Here we demonstrate how iDQCs signal can be used to efficiently detect the anisotropy created in breast tumor tissues and prostate tumor tissues by targeted (LHRH-conjugated) superparamagnetic nanoparticles (SPIONs), thereby distinguishing the necrotic area from the surrounding tumor tissue.

Simultaneous acquisition of multiple orders of intermolecular multiple-quantum coherence images in vivo.

Until recently, NMR imaging with intermolecular multiple-quantum coherences (iMQCs) has been based on the acquisition of a single echo. In vivo studies of iMQC image contrast would greatly benefit from a method that could acquire several orders of quantum coherence during the same acquisition. This would enable comparison of the image contrast for various orders and eliminate image coregistration problems between scans. It has previously been demonstrated that multiple orders of iMQC images can be simultaneously acquired of a simple phantom. Here, we examine the technique and its effect on biological tissue, both in vivo and in vitro. First, we establish the effectiveness of the iMQC sequence in vivo using earthworms as specimens. We then further show that the multi-CRAZED sequence enhances detection of next generation (nanoparticle) contrast agents on excised tumor tissue.