Development of multifunctional Overhauser-enhanced magnetic resonance imaging for concurrent in vivo mapping of tumor interstitial oxygenation, acidosis and inorganic phosphate concentration

Abstract

Tumor oxygenation ( p O 2 ), acidosis (pH) and interstitial inorganic phosphate concentration (Pi) are important parameters of the malignant behavior of cancer. A noninvasive procedure that enables visualization of these parameters may provide unique information about mechanisms of tumor pathophysiology and provide clues to new treatment targets. In this research, we present a multiparametric imaging method allowing for concurrent mapping of pH, spin probe concentration, p O 2 , and Pi using a single contrast agent and Overhauser-enhanced magnetic resonance imaging technique. The developed approach was applied to concurrent multifunctional imaging in phantom samples and in vivo in a mouse model of breast cancer. Tumor tissues showed higher heterogeneity of the distributions of the parameters compared with normal mammary gland and demonstrated the areas of significant acidosis, hypoxia, and elevated Pi content.

Biological Applications of Electron Paramagnetic Resonance Viscometry Using a 13C-Labeled Trityl Spin Probe

“…The EPR spectra of the 13 C-dFT probe recorded after its intratissue injection into the various organs of anesthetized mice exhibited doublet EPR spectra characteristic for the non-immobilized probe only (data not shown). Note that the in vivo half-life time of the probe at the site of measurement was about 30 min, likely due to the clearance from the organ resulting in an accumulation in the bladder [ 29 ]. Figure 5 shows the results of the EPR measurements of the microviscosity of the interstitial fluids in various mouse organs.…”

“…In the last decade, the trityl probes and labels with extended functional sensitivity [48][49][50][51][52][53] were synthesized. Multifunctional trityl probes were used for in vivo concurrent spectroscopy and imaging of tissue pO 2 , pH and interstitial inorganic phosphate, Pi [28,29]. Synthesis of a viscosity-sensitive 13 C-dFT probe further extends the list of the parameters of the local tissue microenvironment assessable by the low-field EPR technique in vivo.…”

Large-scale synthesis of a monophosphonated tetrathiatriarylmethyl spin probe for concurrent in vivo measurement of pO2, pH and inorganic phosphate by EPR

“…5) shows that up to 1 mM, the probe is well tolerated with $80% cell viability aer 24 h. It is worth noting that only a few hundred micromolar range is required for in vivo L-band spectroscopy and the MTT results show no signicant difference between 100 mM of probe and the control. Moreover, pTAM was incubated 24 h with cells while in vivo the probe is cleared from the tissue in less than 1 h. 26 Therefore, the probe can be considered as non-toxic upon local injection, which is the mode of delivery for pTAM. 19…”

Synthesis of hydroxyethyl tetrathiatriarylmethyl radicals OX063 and OX071

“…For this reason, in vivo applications are limited to intra-tissue deliveries only. 6,7,14 On the other hand, OX063 shows a high hydrophilicity due to twelve additional alcohol functions, preventing interactions with biomacromolecules, allowing for a systemic delivery of the probe. 15 Unfortunately, the synthesis of OX063 has not been reported in the scientic literature and its synthesis remained elusive 16 although being commercially available at a very high cost (>$10,000 per g).…”