TY - JOUR
T1 - Dynamic changes in 1H-MR relaxometric properties of cell-internalized paramagnetic liposomes, as studied over a five-day period
AU - Kok, Maarten B.
AU - Strijkers, Gustav J.
AU - Nicolay, Klaas
PY - 2011
Y1 - 2011
N2 - Molecular imaging based on MRI requires the use of amplification strategies in order to achieve sufficient sensitivity for the detection of low-level molecular markers. Recently, we described a combination of two amplification methods: (i) the use of paramagnetic liposomes that can be prepared with a high payload of Gd(3+)-containing lipid; and (ii) targeting to a cell-surface receptor that can undergo multiple rounds of nanoparticle delivery in the cell, followed by recycling to the cell membrane. Liposome uptake was monitored over a period of 24 h and was found to lead to massive delivery in subcellular compartments. The present study aimed to monitor the longer-term fate of the cell-internalized contrast material by studying its relaxometric properties over 5 days, following an initial 24 h loading period. Circa 25% of the Gd(3+)-content delivered to the cells via integrin-targeted liposomes was lost in the first 24 h, which led to 65 and 77% reductions in R(1) and R(2), respectively, as compared with the original R(1) and R(2) enhancements. This implies that the remaining cell-associated gadolinium had relatively low effective r(1) and r(2) relaxivities. It is proposed that this is due to gradual release of Gd(3+) from the chelate in the cell, followed by sequestration in an MR silent state. Most of the gadolinium internalized by cells following incubation with non-targeted liposomes was released in the 5-day follow-up period
AB - Molecular imaging based on MRI requires the use of amplification strategies in order to achieve sufficient sensitivity for the detection of low-level molecular markers. Recently, we described a combination of two amplification methods: (i) the use of paramagnetic liposomes that can be prepared with a high payload of Gd(3+)-containing lipid; and (ii) targeting to a cell-surface receptor that can undergo multiple rounds of nanoparticle delivery in the cell, followed by recycling to the cell membrane. Liposome uptake was monitored over a period of 24 h and was found to lead to massive delivery in subcellular compartments. The present study aimed to monitor the longer-term fate of the cell-internalized contrast material by studying its relaxometric properties over 5 days, following an initial 24 h loading period. Circa 25% of the Gd(3+)-content delivered to the cells via integrin-targeted liposomes was lost in the first 24 h, which led to 65 and 77% reductions in R(1) and R(2), respectively, as compared with the original R(1) and R(2) enhancements. This implies that the remaining cell-associated gadolinium had relatively low effective r(1) and r(2) relaxivities. It is proposed that this is due to gradual release of Gd(3+) from the chelate in the cell, followed by sequestration in an MR silent state. Most of the gadolinium internalized by cells following incubation with non-targeted liposomes was released in the 5-day follow-up period
U2 - https://doi.org/10.1002/cmmi.406
DO - https://doi.org/10.1002/cmmi.406
M3 - Article
C2 - 20936712
SN - 1555-4309
VL - 6
SP - 69
EP - 76
JO - Contrast media & molecular imaging
JF - Contrast media & molecular imaging
IS - 2
ER -