title: Feasibility Evaluation of Detecting Hydroxymethylphosphine Oxide In Vivo by (31)P-MRS.
abstract: Application of organophosphorus compounds in biomedicine is attractive because the (31)P nucleus is very amenable to study by nuclear magnetic resonance (NMR) techniques, particularly, by in vivo (31)P magnetic resonance spectroscopy ((31)P-MRS). The water-soluble organophosphorus compounds that are non-toxic, exhibit metabolic stability, and show a unique resonance peak in (31)P NMR spectroscopy, which could be ideal to be used as probes for (31)P-MRS. Here we evaluated the in vivo feasibility of potentially using a hydroxymethylphosphine oxide as a novel probe for (31)P-MRS studies using tris (hydroxymethyl) phosphine oxide (THPO) as an example. THPO was synthesized, injected in the normal CF1 mice, and (31)P spectra were acquired before and after injection with the coil located on the regions of interest. The NMR signal from the region of interest appeared within one minute of THPO injection. The compound was stable in vivo as no metabolites of THPO were observed. No toxicity was observed after THPO injection in mice. The peak concentrations of THPO in liver and kidney were reached within 15 min and 60 min respectively. THPO was excreted exclusively in urine without undergoing any metabolism indicating that it is very stable under in vivo conditions. These initial studies in normal CF1 mice clearly demonstrate that THPO possess the essential characteristics required for a potential MRS probe. Based on the current preliminary results, we suggest that HMPs, when incorporated into targeted drugs (peptides, proteins, antibodies, etc.), may serve as novel (31)P probes for monitoring the drug distribution in vivo by MRS.
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, 825 NE 13th street, Oklahoma City, Oklahoma, USA;
authors.forename: Sabrina
authors.initials: S
authors.lastname: Doblas
authors.forename: Gopal
authors.initials: G
authors.lastname: Pathuri
authors.forename: Rheal A
authors.initials: RA
authors.lastname: Towner
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Gali
keywords: 31P-MRS; MRI; NMR; hydroxymethylphosphine oxide