Key result
High-pressure plasmid DNA limb injections in primates demonstrate MRI-monitored muscle distribution and transient vascular effects.
MRI and MRA can effectively monitor the distribution and vascular effects of high-pressure intravascular plasmid DNA injections in primate limbs.
MRI monitoring of plasmid delivery is feasible in primates; leaves open translation to human gene therapy.
The purpose of this work is to investigate the use of magnetic resonance imaging (MRI) to monitor the effects of high-pressure naked plasmid DNA (pDNA) intravascular injections in primate limbs, studying both the distribution of the injected solution in the muscle space, as well as the effects on the vascular system. The distal portion of the four limbs of each of six rhesus monkeys were hydrodynamically injected with naked pDNA, which expressed the luciferase reporter gene. Three-dimensional (3D) T1-weighted gradient echo and 2D multislice T2-weighted fast spin echo (FSE) series were acquired before and immediately after the injection to confirm the volume of solution injected into the limb, and to study the distribution of the injected solution in the individual muscle groups. Time-resolved contrast-enhanced 3D magnetic resonance angiography (MRA) was performed several days before, immediately after, and in a follow-up examination after the pDNA injection to study the effects of the procedure on the primate peripheral vascular system. T1-weighted gradient echo imaging confirmed the delivery of the majority of the solution after successful pDNA injections. T2-weighted FSE imaging demonstrated the distribution of the saline solution in individual muscles in the target limbs, with enhancement showing a weak but significant correlation with the level of gene expression. Time-resolved contrast-enhanced MRA demonstrated effects of the injection procedure on the arterial and venous vascular systems, and the intramuscular compartments; and these effects largely returned to normal on short-term follow-up.
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Vigen et al. (2007) studied this question. High-pressure naked plasmid DNA (pDNA) intravascular injections was evaluated on Distribution of the injected solution in the muscle space and effects on the vascular system. High-pressure naked plasmid DNA intravascular injections in primate limbs were successfully monitored by MRI, demonstrating solution distribution in target muscles and transient vascular effects.
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