TmDOTP(5-) as a (23)Na shift reagent for the subcutaneously implanted 9L gliosarcoma in rats

Area of Science:

• Biomedical Imaging
• Magnetic Resonance Imaging
• Tumor Biology

Background:

• In vivo sodium-23 NMR spectroscopy is crucial for assessing tumor physiology.
• Developing reliable shift reagents (SRs) and extracellular space (ECS) markers is essential for accurate sodium MRI.
• Thulium diethylenetriaminepentaacetic acid (TmDOTP(5-)) is a potential candidate for these applications.

Purpose of the Study:

• To evaluate TmDOTP(5-) as an in vivo (23)Na NMR shift reagent and ECS marker in a 9L gliosarcoma tumor model.
• To assess the biodistribution and impact of TmDOTP(5-) on tumor bioenergetic status.
• To compare TmDOTP(5-) with a known ECS marker, Cobalt-EDTA (CoEDTA(-)).

Main Methods:

• Administered TmDOTP(5-) intravenously to rats bearing subcutaneous 9L gliosarcoma.
• Utilized (23)Na and (31)P NMR spectroscopy to monitor spectral changes.
• Measured relative extracellular space and intracellular sodium concentration.
• Determined in vivo T(1) and T(2) relaxation times of intra- and extracellular sodium.

Main Results:

• TmDOTP(5-) produced a distinct extracellular (23)Na peak within 50-60 minutes post-infusion.
• No significant alterations in (31)P NMR spectra indicated no impact on tumor bioenergetics.
• TmDOTP(5-) and CoEDTA(-) yielded comparable values for relative ECS (0.25) and intracellular Na+ concentration (~19 mM).
• In vivo relaxation times (T(1), T(2)) for intra- and extracellular Na+ were successfully measured.

Conclusions:

• TmDOTP(5-) is a safe and effective in vivo (23)Na NMR shift reagent for 9L gliosarcoma.
• Its biodistribution matches that of established ECS markers.
• TmDOTP(5-) holds promise as a valuable tool for studying ECS and sodium dynamics in tumors.