Myelin‐targeted, texaphyrin‐based multimodal imaging agent for magnetic resonance and optical imaging

Abstract

Reliable methods of imaging myelin are essential to investigate the causes of demyelination and to study drugs that promote remyelination. Myelin-specific compounds can be developed into imaging probes to detect myelin with various imaging techniques. The development of multimodal myelin-specific imaging probes enables the use of orthogonal imaging techniques to accurately visualize myelin content and validate experimental results. Here, we describe the synthesis and application of multimodal myelin-specific imaging agents for light microscopy and magnetic resonance imaging. The imaging agents were synthesized by incorporating the structural features of luxol fast blue MBS, a myelin-specific histological stain, into texaphyrins coordinated to GdIII. These new complexes demonstrated absorption of visible light, emission of near-IR light, and relaxivity values greater than clinically approved contrast agents for magnetic resonance imaging. These properties enable the use of optical imaging and magnetic resonance imaging for visualization of myelin. We performed section- and en block-staining of ex vivo mouse brains to investigate the specificity for myelin of the new compounds. Images obtained from light microscopy and magnetic resonance imaging demonstrate that our complexes are retained in white matter structures and enable detection of myelin.

Novel ionization processes for use in mass spectrometry: ‘Squeezing’ nonvolatile analyte ions from crystals and droplets

“…Using an i MAI‐IMS‐MS approach, structural information was obtained by cross‐section analyses of the folding transitions of lysozyme, a protein associated with neurodegenerative diseases . We demonstrated analytical examples where conventional MALDI was difficult or failed, while MAI produced the desired results providing a molecular view of, e.g., endogenous and exogenous chemical compositions . Importantly, irrespective of the new methods employed to engage with the new ionization processes, ESI‐like charge states are observed.…”

“…Therefore, the charging and desolvation are associated with the matrix:analyte traversing through the cold or hot inlet tube, reducing the ion source to a feature intrinsically available with any atmospheric pressure ionization mass spectrometer without having to apply additional energy. A variety of different commercial MALDI and ESI sources have been employed for LSI and imaging applications including those from Thermo, Waters, and Bruker mass spectrometers . Recently, a miniature portable mass spectrometer was fitted with an LSI source …”

Metalloporphyrins in Medicine: From History to Recent Trends

“…Unfortunately, high liver accumulation of Gd-hematoporphyrin evidenced free-Gd leakage, but in 1996, Young and colleagues designed a P derivative, called texaphyrin, with a larger internal cavity containing five nitrogen atoms, which reduced Gd leakage completely . Later, many research groups used texaphyrins in MRI probes design. − Further pursuing of Gd complexes stabilization led to development of Ps containing external chelators (DOTA, DTPA) that have been attached to the P core. These complexes, developed first in 1999 by Hofmann and colleagues, still represents a relevant group in a modern Gd-porphyrin based MRI probe design. − …”

Effect of Paramagnetic Open-Shell Gadolinium(III) Texaphyrin on Its Kinetics and Electronic Structures in Fluorescence and Phosphorescence Emission States

“…, respectively (note that the state in the bracket indicates where the Γ state comes from, e.g., m+1 Γ i ( 1 S 0 ) denotes that m+1 Γ i is a result of the coupling between the metal electron spin state s = m/2 and the ligand 1 S 0 state (also see Figure S1). Consequently, the ground state, excited singlet, and triplet states of the (closed-shell) diamagnetic molecule Lu(4f 14 )-Tex (m = 0) are just denoted as 1 S 0 , 1 S n , and 3 T n , respectively. However, for the para-magnetic Gd(4f 7 )-Tex (m = 7), the exchange coupling between the Gd(III) 4f electrons (spin s = 7/2) and the texaphyrin ground singlet state 1 S 0 gives rise to an octahedral degenerate set of states 8 Γ i ( 1 S 0 ) (i ≥ 0), and thus, the ground state of Gd-Tex should be the one with the lowest energy and written as 8 Γ 0 ( 1 S 0 ).…”

“…This feature gives texaphyrin great advantages when forming stable metal complexes (metallotexaphyrins). To date, a large variety of metallotexaphyrin have been investigated, and the most interesting molecules are those based on transition and lanthanide metals. − One of their promising applications is concentrated on the biomedical field where, for example, the texaphyrin complexes based on gadolinium­(III) (Gd-Tex) were found to effectively enhance magnetic resonance imaging signals due to the paramagnetic Gd­(III) cation, ,,− while both Gd­(III) and Lu­(III) texaphyrin complexes show potential as excellent photosensitizers in photodynamic therapies to treat cancers. ,,,− Therefore, it is of paramount importance to understand the electronic structures and properties of these complexes, especially when considering their emission properties, which are closely related to their applications. However, unlike metal porphyrin or phthalocyanine complexes where such properties have been extensively studied both experimentally − and theoretically, − experimental measurements for these metallotexaphyrins − regarding their emission properties are quite scarce and only three theoretical works have been found, which investigated the metallotexaphyrin absorption spectra − with a very brief discussion of the emission energies in only one of them .…”