Barbara Blasiak

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive type of pancreatic cancer. PDAC is difficult to diagnose due to a lack of symptoms in early stages, resulting in a survival rate of less than 10%. Moreover, often cancerous tissues cannot be surgically resected due to their deep abdomen location. Therefore, early detection is the essential strategy enabling effective PDAC treatment. Over the past few years, the development of nanomaterials for Magnetic Resonance Imaging (MRI) has expanded and improved imaging quality and diagnostic accuracy. Nanomaterials can be currently designed, manufactured and synthesized with other structures to provide improved diagnosis and advanced therapy. Although MRI equipped with the innovative nanomaterials became a powerful tool for the diagnosis and treatment of patients with various cancers, the detection of PDAC remains challenging. Nevertheless, recent advancements in PDAC theranostics provided progress in the detection and treatment of this challenging type of cancer. Present research in this area is focused on suitable carriers, eliminating delivery barriers, and the development of efficient anti-cancer drugs. Herein we discuss the current applications of iron oxide nanoparticles to the MRI diagnosis and treatment of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive type in pancreatic cancer. PDAC is difficult to diagnose due to lack of symptoms in early stages, resulting in survival of less than 10%. Moreover, often cancerous tissues cannot be surgically resected due to their deep abdomen location. Therefore, early detection is the essential strategy enabling effective PDAC treatment. Over the past few years, the development of nanomaterials for MRI has expanded and improved imaging quality and diagnostic accuracy. Nanomaterials can be currently designed, manufactured and synthesized with other structures to provide improved diagnosis and advanced therapy. Although MRI equipped with the innovative nanomaterials became a powerful tool for diagnosis and treatment of patients with various cancers, detection of PDAC remains challenging. In this review, we discuss the current applications and properties of iron oxide nanoparticles applied for the detection of pancreatic cancer with MRI in clinical environment.

Magnetic resonance imaging (MRI) is widely used as a medical imaging technique due to its non-invasive nature, high spatial contrast, and virtually unlimited depth of penetration. Different modalities can be used for contrast in MRI, including T₁ (spin–lattice) and T₂ or T₂ * (spin–spin) proton relaxation times, and specific contrast agents (CAs) have been developed that locally enhance the contrasts in MRI images. We present a method combining T₁- and T₂-specific CAs in a single imaging technique, referred to as correlation MRI. This technique allows different CAs to be used simultaneously to visualize contrast between multiple types of tissue in the same image when applied as targeted CAs. An obstacle for the quantitative use of correlation MRI is that T₁ and T₂ relaxivity changes generated by CAs are not independent of each other. Here, we measured relaxivities in mixtures with various concentrations of Cas, including Magnevist (Gd³⁺-based, primarily a T₁ CA) and Feridex (Fe²⁺- and Fe³⁺-based, primarily a T₂ CA), and compared them to theoretically predicted values. It was found that, at clinically relevant concentrations, relaxivities of the mixtures deviate from linearly added values. We finally propose a three-dimensional calibration curve to quantitatively determine the concentration in mixtures of CAs, based on the measured relaxivities.

This paper presents the efficacy of a contrast agent based on H₂N-Fe₃O₄ nanoparticles for the detection of prostate cancer in an animal model using a preclinical 9.4 T MRI system. The relaxivities r₁ and r₂ of the nanoparticles were 6.31 mM⁻¹s⁻¹ and 8.33 mM⁻¹s⁻¹, respectively. Nanoparticles injected in a concentration of 2 mg Fe/mL decreased the tumor-relative T₁ relaxation across all animals from 100 to 76 ± 26, 85 ± 27, 89 ± 20, and 97 ± 16 12 min 1 h, 2 h, and 24 h post injection, respectively. The corresponding T₁ decrease in muscle tissues was 90 ± 20, 94 ± 23, 99 ± 12, and 99 ± 14. The relative T₂ changes in the tumor were 82 ± 17, 89 ± 19, 97 ± 14, and 99 ± 8 12 min, 1 h, 2 h, and 24 h post injection, respectively, while, for muscle tissues, these values were 95 ± 11, 95 ± 8, 97 ± 6, and 95 ± 10 at the corresponding time points. The differences in the relative T₁ and T₂ were only significant 12 min after injection (p < 0.05), although a decrease was visible at each time point, but it was statistically insignificant (p > 0.05). The results showed the potential application of H₂N-Fe₃O₄ nanoparticles as contrast agents for enhanced prostate cancer MRI.

Gd- and Fe-based contrast agents reduce T₁ and T₂ relaxation times, respectively, are frequently used in MRI, providing improved cancer detection. Recently, contrast agents changing both T₁/T₂ times, based on core/shell nanoparticles, have been introduced. Although advantages of the T₁/T₂ agents were shown, MR image contrast of cancerous versus normal adjacent tissue induced by these agents has not yet been analyzed in detail as authors considered changes in cancer MR signal or signal-to-noise ratio after contrast injection rather than changes in signal differences between cancer and normal adjacent tissue. Furthermore, the potential advantages of T₁/T₂ contrast agents using image manipulation such as subtraction or addition have not been yet discussed in detail. Therefore, we performed theoretical calculations of MR signal in a tumor model using T₁-weighted, T₂-weighted, and combined images for T₁-, T₂-, and T₁/T₂-targeted contrast agents. The results from the tumor model are followed by in vivo experiments using core/shell NaDyF₄/NaGdF₄ nanoparticles as T₁/T₂ non-targeted contrast agent in the animal model of triple negative breast cancer. The results show that subtraction of T₂-weighted from T₁-weighted MR images provides additional increase in the tumor contrast: over two-fold in the tumor model and 12% in the in vivo experiment.

The novel iron-oxide nanoparticles (NPs) stabilized with triethanolammonium oleate were produced. The specimens were divided into two groups: the top NPs (extracted from the supernatant) and the bottom NPs (nanoparticles sedimented at the bottom of the flask during centrifugation), respectively. The XRD and Mössbauer studies revealed a presence of the Fe₃O₄ phase in both types of nanoparticles. Furthermore, the formation of maghemite layer on the surface of nanoparticles was observed. Average particle sizes determined from TEM and XRD studies were lower than the superparamagnetic limit for the magnetite NPs. For glycerol dispersions of both types of NPs, when exposed to 100 kHz external magnetic field, a significant heat release was observed. Furthermore, the contrasts of T₁- and T₂-weighted MR images were significantly dependent on the concentration of NPs in their water solutions. Additionally, the reductions of the relaxation times were different for the top and the bottom NPs. The viability studies of the colon cancer cells have shown low cytotoxicity of both types of NPs due to their coating with triethanolammonium oleate, which confirm the possibility to apply the NPs for MRI-guided hyperthermia. Moreover, the presence of NPs did not cause greatest increase of the number of apoptotic cells in the human dermal fibroblasts’ culture and has stimulated proliferation of those cells, revealing great potential of the NPs in regenerative medicine. Graphical abstract