Macromolecular infarct-specific magnetic resonance contrast agents.
OBJECTIVE
To identify safe and effective magnetic resonance imaging (MRI) agents for infarction, the authors investigate the possibility of using a small population of infarct-avid phosphonates to target macromolecular MRI agents to infarction.


METHODS
Several phosphonylated radiolabeled (gadolinium-153, iron-59) macroaggregates were synthesized. Biodistribution was assessed in a drug-induced rat model of diffuse myocardial infarction (MI). Agents that demonstrated preferential accumulation in infarcted whole hearts were additionally evaluated in occluded and reperfused rabbit hearts. Phosphonylated T2 agents have been thoroughly studied with MRI of MI, and the results are reported.


CONCLUSIONS
Typically, core size was 11 to 13 nm and particle size was 120 nm. Phosphorus content was < 12% by weight. The relaxivities were R1 of 12 to 20 1/(mM.sec) and R2 of 119 to 270 1/(mM.sec) at 20 MHz in .5% agar. One hour after injection of .03 mmol/kg of the agent into six rabbits (45-minute occlusion with 1-hour reperfusion), the average myocardial tissue agent content was 70 +/- 30 nmol Fe/g (infarct) compared with 9 +/- 2 nmolFe/g (normal); P = .000. Similarly, the infarct zone was clearly discerned by MRI as hypointense on spin echo images, TR/TE = 400/30 msec and 2,000/30 msec with low-dose agent, whereas infarct was barely discernible only on TR/TE = 2,000/90 msec without agent. The magnetic resonance infarcts correlated with histology.


CONCLUSIONS
Simple phosphonylated macromolecules can be used as low-dose, infarct-specific MRI agents.
Adzamli
K
K
Department of Radiology, University of Massachusetts Medical Center, Worcester.
Mei
H
H
Leppo
J A
JA
D000818:Animals; D003287:Contrast Media; D005682:Gadolinium; D007504:Iron Radioisotopes; D046911:Macromolecular Substances; D008279:Magnetic Resonance Imaging; D008297:Male; D009203:Myocardial Infarction / Q000175:diagnosis*; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D011868:Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D007504:Iron Radioisotopes; D046911:Macromolecular Substances; D011868:Radioisotopes; D005682:Gadolinium