Preclinical evaluation of MnDPDP: new paramagnetic hepatobiliary contrast agent for MR imaging.
Manganese(II)-N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis (phosphate) (MnDPDP) is a paramagnetic complex designed for use as a hepatobiliary agent. The T1 relaxivity of MnDPDP (2.8 [mmol/L]-1.sec-1 in aqueous solution) was similar to that of gadolinium diethylenetriaminepentaacetic acid (DTPA) (4.5 [mmol/L]-1.sec-1) and gadolinium tetraazocyclodecanetetraacetic acid (DOTA) (3.8 [mmol/L]-1.sec-1). However, in liver tissue the T1 relaxivity of MnDPDP (21.7 [mmol/L]-1.sec-1) was threefold higher than that reported for Gd-DOTA (6.7 [mmol/L]-1.sec-1). Maximum liver T1 relaxation enhancement occurred 30 minutes after injection of MnDPDP, at which time 54MnDPDP biodistribution studies indicated that 13% of total body activity was in the liver. Enhanced (MnDPDP, 50 mumol/kg) MR images showed a fivefold increase in tumor-liver contrast-to-noise ratio over baseline unenhanced images. Results of the authors' acute and subchronic toxicity studies suggest that MnDPDP will be safe at the doses necessary for clinical imaging; at 10 mumol/kg, the safety factor (LD50/effective dose) for MnDPDP is 540, significantly greater than the safety factor of Gd-DTPA (ie, 60-100).
Elizondo
G
G
Department of Radiology, Massachusetts General Hospital, Boston.
Fretz
C J
CJ
Stark
D D
DD
Rocklage
S M
SM
Quay
S C
SC
Worah
D
D
Tsang
Y M
YM
Chen
M C
MC
Ferrucci
J T
JT
D000818:Animals; D003287:Contrast Media; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004492:Edetic Acid / Q000633:toxicity / Q000031:analogs & derivatives; D005260:Female; D007928:Lethal Dose 50; D008099:Liver / Q000033:anatomy & histology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese; D020149:Manganese Poisoning; D051379:Mice; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D014018:Tissue Distribution
D003287:Contrast Media; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid