Orotracheal manganese‐enhanced MRI (MEMRI): An effective approach for lung tumor detection

Abstract

Lung cancer is a primary cause of cancer deaths worldwide. Timely detection of this pathology is necessary to delay or interrupt lung cancer progression, ultimately resulting in a possible better prognosis for the patient. In this context, magnetic resonance imaging (MRI) is especially promising. Ultra-short echo time (UTE) MRI sequences, in combination with gadolinium-based contrast agents, have indeed shown to be especially adapted to the detection of lung neoplastic lesions at submillimeter precision. Manganese-enhanced MRI (MEMRI) increasingly appears to be a possible effective alternative to gadolinium-enhanced MRI. In this work, we investigated whether low-dose MEMRI can effectively target non-small-cell lung cancer in rodents, whilst minimizing the potential toxic effect of manganese. Both systemic and orotracheal administration modalities allowed the identification of tumors of submillimeter size, as confirmed by bioluminescence imaging and histology. Equivalent tumor signal enhancements and contrast-to-noise ratios were observed with orotracheal administration using 20 times lower doses compared with the more conventional systemic route. This finding is of crucial importance as it supports the observation that higher performances of contrast agents can be obtained using an orotracheal administration route when targeting lung diseases. As a consequence, lower concentrations of contrast media can be employed, reducing the dose and potential safety issues. The non-detectable accumulation of ionic manganese in the brain and liver following orotracheal administration observed in vivo is extremely encouraging with regard to the safety of the orotracheal protocol with low-dose Mn administration. To our knowledge, this is the first time that a study has clearly allowed the high-precision detection of lung tumor and its contours via the synergic employment of a strongly T -weighted MRI UTE sequence and ionic manganese, an inexpensive contrast agent. Overall, these results support the growing interest in drug and contrast agent delivery via the airways to target and diagnose several diseases of the lungs.

Aerosolised micro and nanoparticle: formulation and delivery method for lung imaging

“…Besides the clinical application, nebuliser can also be used for development study of a new contrast agent administration via pulmonary delivery, including AuNP [110], gadolinium nanoparticle (GdNP) [16,34,111], Iodine-based contrast agent (I-CA) [18], MnCl 2 [112], silver nanoparticle (AgNP) [23,24], and superparamagnetic iron oxide nanoparticle (SPION) [17,113]. Such a study aimed to determine lung deposition and clearance [111], investigate biokinetics and toxicity [110,112], and evaluate the lung image quality generated after inhalation [16,18].…”

A Review on the Design of Carbon-Based Nanomaterials as MRI Contrast Agents

“…In view of Gd complexes' issues, researchers are continually developing alternatives with an equal or higher efficiency (Figure 1). Other than using GBCAs, manganese-based MRI contrast agents are increasingly emerging as potentially safer alternatives for manganese-enhanced MRIs (MEMRI) [8][9][10]. Molecular Mn-based contrast agents behave similarly to Gd complexes, i.e., their safe use in the clinic is enabled by their complexation with chelating ligands.…”

Assessment of cardiac toxicity of manganese chloride for cardiovascular magnetic resonance

“…Manganese has atomic structural similarities to calcium and can enter cardiomyocytes through voltage-gated calcium channels, allowing intracellular distinction of living cells (Ochi, 1976). Manganese-based contrast agents may thus provide different information than LGE-MRI for various cardiac pathologies, allowing for example visualization of remaining viable tissues inside or around infarcted regions (Hu et al, 2005;Bianchi et al, 2017;Tada et al, 2019). However, high concentration of manganese increases the competition between Mn 2+ and Ca 2+ ions on calcium channels which can lead to myocardial depression (for review see (Brurok et al, 1997)).…”