**1. Introduction**

Due to their capacity to give anatomical (mainly dimensions) and functional characteristics of solid tumors and their environs, imaging biomarkers are becoming more crucial in cancer research. The characteristics of metabolism, tissue water diffusion, perfusion, chemical composition, and hypoxia are among those that PET, CT, and MRI may measure. Anatomical and functional information (physiological and pathophysiological) are only available with MRI, making it special. Noninvasive imaging probes like nanoparticles (NPs) have a lot of potential in this

field of study because they can be made to carry and release anticancer medications into the target tissue while also functioning as diagnostic tools by utilizing the physical and chemical properties of their constituents (or moieties) [1–4]. While further acting as tools for diagnosis. Clinical trial imaging biomarker-based response criteria ought to aid in directing early choices and reducing the likelihood that patients would get needless treatment. Size-based response assessment is typically ineffective in detecting responses in patients who are experiencing either cytostasis or pseudoprogression because it is frequently insensitive to early biological alterations. These situations are typically seen with innovative target therapy, where the cancer response is more variable than with cytotoxic drugs. Biological changes such apoptosis, necrosis, cystic degeneration, intralesional hemorrhage, edoema, and immune cell infiltration happen quickly after the start of treatment (up to 12 weeks later). It is possible that anatomical imaging would not be able to identify them, which could affect clinical outcomes. Judgment. Many of these modifications can be seen on MRI and may serve as preliminary therapeutic response indications. As a result, there is an urgent demand for particular MRI biomarkers for cutting-edge treatments.

This study will concentrate on one of the most fascinating uses of NPs in cancer imaging, specifically their role in the early evaluation of immunotherapy efficacy and their capacity to change macrophage polarization.

A cutting-edge therapeutic strategy called immunotherapy works by inducing an immunological response in cancer cells. The recruitment of immune cells to the tumor site, which may be accompanied by a decline in tumor growth, is a sign of an early response to immunotherapy. NPs' propensity to be internalized by inflammatory cells in vivo is correlated with their ability to act as diagnostic agents [5]. Their capacity to be internalized by various cells, both in vitro and in vivo, has been utilized for a variety of purposes throughout the previous 20 years.

As will be briefly stated in the first half of this study, the ability of iron oxide NPs to penetrate cells, including stem cells, can enable MRI detection of inflammatory cell recruitment and provide information on the fate of the cells when transplanted into living beings. Applications in cancer immunotherapies will be highlighted in the sections that follow. The final section of the study will focus on magnetic particle imaging (MPI), a cutting-edge tomographic imaging technique that uses iron oxide nanoparticles (NPs) as tracers and describes how iron oxide NPs can be directed toward lesions. MPI is anticipated to have a significant diagnostic role in cancer immunotherapy due to its high sensitivity.

### **2. Contrast-enhancing iron oxide nanoparticles for cellular imaging**

Several iron-based MR contrast agents were created for MRI in the middle of the 1990s. They were referred to as ferrites, magnetites, ferumoxides, or superparamagnetic iron oxides (SPIOs) because they were often made up of tiny (30–200 nm) clusters of iron-containing crystals that formed single magnetic domains. Iron-based MR contrast agents are referred to as T2-relaxing contrast agents because they have higher transverse relaxivity and r2/r1 ratios than Gd chelates. They can also have a considerable effect on the T2 relaxation time since they considerably increase the inhomogeneity of the static magnetic field outside of their immediate neighborhood. On T2 weighted pictures taken close to the iron, iron oxide NPs therefore cause a signal attenuation (commonly referred to as the "blooming effect") [6].

#### *Iron Oxide Nanoparticles: A Mighty Pioneering Diagnostic Tool But Is It Really Safe… DOI: http://dx.doi.org/10.5772/intechopen.112074*

Iron oxide nanoparticles (NPs) have been suggested as liver-specific contrast agents due to their size and affinity for collection by the reticuloendothelial system of the liver following intravenous injection [7]. Due to the variety of cells' ease of internalization, iron oxide nanoparticles (NPs) have been employed extensively during the past 20 years to identify and track cells administered as therapy for various disorders. A detailed summary of the experiment's approach, states that NPs are given to the medium for cell growth, maybe coupled with transfection agents. In terms of cellular iron content and cell survival, the ideal experimental parameters, such as incubation period, iron oxide NP concentration, and transfection agent addition, are identified.

Using MRI, the cells are tracked in vivo after being injected into the recipient's body [8]. The fate of many cell types, including stem cells [9–11], pancreatic islets [12, 13], dendritic cells [14], and even exosomes generated from stem cells [15, 16], has been investigated using this approach in a number of preclinical studies. Benefits and limitations of the approach have been demonstrated in preclinical research. The benefits of MRI include its high sensitivity, which can even detect single cells [17, 18], as well as its outstanding anatomical detail, which clarifies cell homing and allows transferability to the clinical setting [19].

The main drawbacks include the inability to differentiate between live and dead cells, the fact that MRI's signal void does not quantitatively report on the number of cells, label dilution due to in vivo cell replication, and the removal of iron oxide NPs that were previously approved for use as MRI contrast agents in clinical settings. Kostevšek et al. [20] provides information on the most recent list of iron oxide (IO)-based contrast agents that have undergone clinical studies or received approval for use as MRI contrast agents as well as specifics on their intended purpose and current market position.

Another possibility is that SPIOs are absorbed by cells in vivo, where circulating monocytes that can enter tumors and transform into macrophages phagocytose iron oxide NPs that have been injected into the circulation. Consequently, immune cell recruitment in malignancies as well as in other organs and tissues can be detected using MRI. In a recent study, Kirschbaum et al. [21] have used high-field MRI to map inflammatory infiltrates in an experimental multiple sclerosis model using iron oxide NPs for cell tracking. They discovered an association between NP absorption and the innate immune cells-only disease's clinical severity. Their research opens the door for more accurate clinical and diagnostic treatment of a range of inflammatory diseases. in addition to therapeutic oversight [22]. Similar techniques have been applied in organ transplant experimental models, where the recruitment of macrophages is one indicator of transplant rejection. Additionally, studies have been done in clinical settings. In a recent clinical investigation, myocardial edoema and macrophage inflammation have been successfully visualized in patients who suffered myocardial infarction, utilizing T2 mapping and Ultrasmall SPIO-enhanced T2 MRI. The study concludes by showing that the technology can offer a noninvasive way to detect and track tissue inflammatory macrophage activity in the heart [23]. It is common practice to use iron oxide NPs to detect macrophages in solid tumors. This is because iron oxide NPs are not antibodyconjugated and can be administered directly into the vein and detected using a conventional 1 H radiofrequency coil and a T2 weighted sequence since they are primarily taken up by phagocytic cells like macrophages and Kupffer cells. To detect the spatial distribution of tumor-associated macrophages (TAMs) and quantify the amount of iron deposition, it is possible to collect a T2 map using a multi-gradient echo sequence. As an alternative, quantitative susceptibility mapping can be used to gauge the change in susceptibility brought about by the treatment by the contrast substance. Both of these methods have a linear correlation with the concentration of iron oxide NPs.
