Solid state NMR is a powerful tool to probe membrane protein structure and motions in native lipid structures. Sample heating, caused by magic angle spinning and radio frequency irradiation in solid state NMR, produces uncertainties in sample temperature and thermal broadening caused by temperature distributions, which can also lead to sample deterioration. To measure the sample temperature in real time, and to quantify thermal gradients and their dependence on radio frequency irradiation or spinning frequency, we use the chemical shift thermometer TmDOTP, a lanthanide complex. Compared to other NMR thermometers (e.g., the proton NMR signal of water), the proton spectrum of TmDOTP exhibits higher thermal sensitivity and resolution. In addition, the H6 proton in TmDOTP has a large chemical shift (−175 ppm at 275 K) and is well resolved from the rest of the proton spectrum. We identified two populations of TmDOTP, with differing temperatures and dependency on the radio frequency irradiation power, within proteoliposome samples. We interpret these populations as arising from the supernatant and the pellet, which is sedimented from the sample spinning. Our results indicate that TmDOTP is an excellent internal standard for monitoring temperatures of biophysically relevant samples without distorting their properties.

Since brain’s microvasculature is compromised in gliomas, intravenous injection of tumor-targeting nanoparticles containing drugs (D-NPs) and superparamagnetic iron oxide (SPIO-NPs) can deliver high payloads of drugs while allowing MRI to track drug distribution. However, therapeutic effect of D-NPs remains poorly investigated because superparamagnetic fields generated by SPIO-NPs perturb conventional MRI readouts. Because extracellular pH () is a tumor hallmark, mapping is critical. Brain is measured by biosensor imaging of redundant deviation in shifts (BIRDS) with lanthanide agents, by detecting paramagnetically shifted resonances of nonexchangeable protons on the agent. To test the hypothesis that BIRDS-based readout remains uncompromised by presence of SPIO-NPs, we mapped in glioma-bearing rats before and after SPIO-NPs infusion. While SPIO-NPs accumulation in the tumor enhanced MRI contrast, the inside and outside the MRI-defined tumor boundary remained unchanged after SPIO-NPs infusion, regardless of the tumor type (9L versus RG2) or agent injection method (renal ligation versus coinfusion with probenecid). These results demonstrate that we can simultaneously and noninvasively image the specific location and the healing efficacy of D-NPs, where MRI contrast from SPIO-NPs can track their distribution and BIRDS-based can map their therapeutic impact.

S Maritim, D Coman, Y Huang, JU Rao, JJ Walsh, F Hyder, Contrast media & molecular imaging, 2017 - Cited by 11

S Maritim, D Coman, Y Huang, JU Rao, JJ Walsh, F Hyder, Contrast media & molecular imaging, 2017 - Cited by 11

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D Coman, DC Peters, JJ Walsh, LJ Savic, S Huber, AJ Sinusas, MD Lin, J Chapiro, RT Constable, DL Rothman…, Magnetic resonance in medicine, 2020 - Cited by 11

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LJ Savic, IT Schobert, D Peters, JJ Walsh, FM Laage-Gaupp, CA Hamm, N Tritz, LA Doemel, MD Lin, A Sinusas…, Clinical Cancer Research, 2020 - Cited by 13

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J King, E Gibbons, C Graham, J Walsh, Geneva: Picker Institute Europe and University of Oxford, 2013 - Cited by 16