Metal‐Based Nanoparticle Magnetic Resonance Imaging Contrast Agents: Classifications, Issues, and Countermeasures toward their Clinical Translation

Abstract

Over the years, several imaging techniques have been developed to improve alreadyexisting ones, thus, overcoming the obstacles that previous ones failed to overcome. Recently, much energy has been put into developing tools that complement the ability of the current imaging techniques. Imaging probe or contrast agent is one of the well-known tools in this category, which enhance the conspicuousness of images. Researchers have taken the opportunity to work tirelessly on developing imaging probes, which have gone a long way in attaining biological and functional image details of a biological system when used alongside existing imaging techniques. With the advantage of displaying a more detailed view for analyzing biological information and diagnosing diseases, imaging probes are undoubtedly a significant research field in biological and medical sciences.Molecular imaging, a term describing the visualization of specific molecules and molecular transformations that occur during disease activity in a living system using radiological and nuclear medicine, [2] has recently received enormous attention. A tissue or organ is diseased when it depicts characteristics that deviate from its normal functionality or organization. The diseased condition is stimulated by many biochemical processes involving internal and external stimuli from within the cell. Molecular imaging serves as a diagnostic tool for detecting abnormal disease molecules early because it can examine the biochemical adjustments as a normal tissue mutates into a diseased one. Representative imaging techniques include magnetic particle imaging (MPI), [3] positron emission tomography (PET), single-photon emission computed tomography (SPECT), optical imaging, magnetic resonance imaging (MRI), computed tomography (CT) and, ultrasound. [4] These imaging techniques are noninvasive diagnostic platforms that bridge the gap between molecular biology and molecular medicine. They allow examining a living organism to verify effects on multiple organ systems in vivo and help diagnose diseases at preclinical stages. These imaging techniques employ tracers or contrast agents to improve sensitivity. MPI is a tracer imaging modality that instantaneously quantifies the concentration and Metal-based nanoparticles, especially gadolinium, manganese, and iron, have gained ground in the research of magnetic resonance imaging (MRI) contrast agents. Over the years, contrast agents based on these paramagnetic and superparamagnetic nanomaterials have merited keen attention in the biomedical field due to their desired properties such as sizeable magnetic susceptibility, tunable size, easy surface functionalization, low toxicity, etc. Gadolinium-based chelates are the traditional MRI contrast agents in the clinic but require improved relaxivities and pharmacokinetics. Nanoparticles possess a larger surface area, demonstrate a longer retention time in the body, and allow the conjugation of several functional molecules to enhance tumor targeting, making them more advantageous. The pursuit o...

Mn(ii) complex impregnated porous silica nanoparticles as Zn(ii)-responsive “Smart” MRI contrast agent for pancreas imaging

“…[18][19][20] Hence, developing non-gadolinium-based, organ-specific and bioresponsive contrast agents through pH, enzyme action, temperature, and ion reflux has drawn paramount attention for better diagnosis of lesions and for non-invasive pathology. [21][22][23][24] Blood glucose level is one of the factors that control the normal functionality of the human body. 25 The pancreas, a vital gland nestled behind the stomach, secrets glucagon and insulin hormones into the blood to maintain glucose levels.…”

“…18–20 Hence, developing non-gadolinium-based, organ-specific and bio-responsive contrast agents through pH, enzyme action, temperature, and ion reflux has drawn paramount attention for better diagnosis of lesions and for non-invasive pathology. 21–24…”

Reticular Chemistry of the Fcu‐Type Gd(III)‐Doped Metal–Organic Framework for T1‐Weighted Magnetic Resonance Imaging

“…Gadolinium-based contrast agents (GBCAs) refer to a class of Gd(III)-species that can shorten the longitudinal relaxation time of surrounding water protons to produce T 1 -weighted magnetic resonance imaging (MRI). [1,2] Although small molecular GBCAs have been widely studied and used for MRI, [3][4][5][6] they still suffer low sensitivity and high doses requirement as well as poor penetration and short retention time due to their discrete molecular feature. [7][8][9] These limitations have led to the emerging interest in exploring their nanoscale aggregates, among which the DOI: 10.1002/smll.…”

High spin Fe(III)‐doped nanostructures as T1 MR imaging probes

“…NPs with well-defined size and shape can be designed and synthesized. The overall size of the NPs is a relevant parameter to be considered as it largely determines their fate in vivo: those with a mean diameter below 5 nm are usually eliminated through renal excretion, whereas larger particles (>100 nm) are easily taken up by macrophages and then undergo hepatobiliary excretion (Antwi-Baah et al, 2022;Das, 2021;Doane & Burda, 2012;Gao et al, 2016;Key & Leary, 2014;Smith & Gambhir, 2017). Among the imaging techniques, Magnetic Resonance Imaging (MRI) is a non-invasive diagnostic modality with excellent contrast ability and high spatial and temporal resolution that provides detailed information about soft tissues and organs.…”

“…NPs with well‐defined size and shape can be designed and synthesized. The overall size of the NPs is a relevant parameter to be considered as it largely determines their fate in vivo: those with a mean diameter below 5 nm are usually eliminated through renal excretion, whereas larger particles (>100 nm) are easily taken up by macrophages and then undergo hepatobiliary excretion (Antwi‐Baah et al, 2022; Das, 2021; Doane & Burda, 2012; Gao et al, 2016; Key & Leary, 2014; Smith & Gambhir, 2017).…”