Non-invasive magnetic resonance thermometry using thulium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (TmDOTA^-)

Abstract

Non-invasive thermometry is pivotal to the future advances of regional hyperthermia as a cancer treatment modality. Current magnetic resonance (MR) thermometry methods suffer from poor thermal resolution due to relatively weak dependence of chemical shift of the 1 H water signal on temperature. This study evaluated the feasibility of using thulium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (TmDOTA^-) for MR thermometry. TmDOTA^- is non-toxic and the gadolinium complex of DOTA^4- is widely used as a MR contrast agent. The results demonstrate that the temperature dependence of the TmDOTA^- proton shifts are about two orders of magnitudes higher than the water proton and, thus, provide excellent accuracy and resolution. In addition, TmDOTA - proton shifts are insensitive to the paramagnetic complex concentration, pH, Ca²⁺ or presence of plasma macromolecules and ions. Because hyperthermia is known to produce changes in tissue pH and other physiological parameters, these properties of TmDOTA^- greatly simplify the procedures for using the lanthanide complex for MR thermometry. Application of TmDOTA^- for measurement of temperature in a subcutaneously implanted human melanoma xenograft is demonstrated. Finally, the feasibility of imaging one of the ¹H resonances of the lanthanide complex is demonstrated in phantom experiments. Overall, TmDOTA^- appears to be a promising probe for MR thermometry in vivo.

• Words
• Temperature
• Tmdota- Complex
• H Magnetic Resonance Spectroscopy