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Relaxation enhancement using liposomes carrying paramagnetic species
Abstract:
Studies were performed to investigate the effects upon the relaxation times of mouse organs of intravenously administered Mn-DTPA entrapped in multilamellar liposomes, Mn-DTPA, 0.9% NaCl entrapped in liposomes, 0.9% NaCl. Manganese concentrations in injectates and tissues were assessed with 54Mn and atomic absorption. T1 and T2 of freshly excised tissues were measured in an NMR spectrometer at 20 MHz and 37% C with IR and CPMG sequences. Entrapment of Mn-DTPA in liposomes increased 54Mn accumulation in liver by 207% and in spleen 1208% and reduced 54Mn in heart by 20% and in kidney by 24% relative to free Mn-DTPA. Statistically significant increases in relaxation rates were produced. However, the increase in relaxation rate per unit concentration of Mn in tissue is reduced by 31% in liver and 62% in spleen when Mn is delivered inside liposomes. These observations have implications for the design of NMR contrast agents.
Insights
Liposome-encapsulated manganese diethylenetriaminepentaacetic acid (Mn-DTPA) alters mouse organ relaxation times. Liposomal delivery impacts manganese biodistribution and relaxation efficiency for potential MRI contrast agents.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Pharmacology
Background:
- Magnetic Resonance Imaging (MRI) relies on contrast agents to enhance image quality.
- Manganese diethylenetriaminepentaacetic acid (Mn-DTPA) is a potential MRI contrast agent.
- Liposomes are versatile nanocarriers for drug and contrast agent delivery.
Purpose of the Study:
- To investigate the biodistribution and effects of Mn-DTPA encapsulated in multilamellar liposomes on mouse organ relaxation times.
- To compare the efficacy of liposomal Mn-DTPA with free Mn-DTPA as an MRI contrast agent.
Main Methods:
- Intravenous administration of Mn-DTPA entrapped in multilamellar liposomes, free Mn-DTPA, and controls (liposomes with 0.9% NaCl) in mice.
- Quantification of manganese concentrations in injectates and tissues using 54Mn radiotracer and atomic absorption spectroscopy.
- Measurement of T1 and T2 relaxation times of freshly excised organs using Nuclear Magnetic Resonance (NMR) spectroscopy at 20 MHz and 37°C with Inversion Recovery (IR) and Carr-Purcell-Meiboom-Gill (CPMG) sequences.
Main Results:
- Liposomal encapsulation significantly altered Mn-DTPA biodistribution: increased 54Mn accumulation in liver (+207%) and spleen (+1208%), while reducing it in heart (-20%) and kidney (-24%) compared to free Mn-DTPA.
- Statistically significant increases in tissue relaxation rates were observed.
- The relaxivity (increase in relaxation rate per unit concentration of Mn) was reduced by 31% in the liver and 62% in the spleen when Mn-DTPA was delivered via liposomes.
Conclusions:
- Liposomal encapsulation of Mn-DTPA modifies its biodistribution and tissue accumulation.
- While liposomal delivery affects manganese distribution, it reduces the efficiency of Mn-DTPA as a contrast agent in certain organs.
- These findings provide crucial insights for the rational design of novel liposome-based MRI contrast agents with optimized biodistribution and efficacy.