Preclinical evaluation of gadolinium (III) texaphyrin complex. A new paramagnetic contrast agent for magnetic resonance imaging.
OBJECTIVE
Gadolinium III texaphyrin (Gd[III] texaphyrin) complex, a new magnetic resonance imaging contrast (MRI) agent, was evaluated.


METHODS
In vitro relaxivity (1.5 T) and stability studies (5% dextrose) were conducted. Subchronic toxicity (8 males, 8 females; 2-20 mumol Gd(III) texaphyrin complex/kg body weight; 3 times per week for 3 weeks). Biodistribution and excretion studies were conducted in Sprague-Dawley rats; MRI studies were conducted in normal and tumor-bearing rats and rabbits.


RESULTS
Relaxivity values were as follows: r1 = 19 (mumol/L.sec)-1 and r2 = 22 (mumol/L.sec)-1. The 21-day subchronic toxicity study revealed no abnormalities. The compound is stable. Biodistribution demonstrated liver uptake. Magnetic resonance imaging in normal (n = 34) and tumor-bearing (n = 4) rats and normal (n = 8) and tumor-bearing (n = 19) rabbits revealed: significant (P < .05) contrast enhancement of liver and kidney after 1-17 mumol/kg of Gd(III) texaphyrin complex. Gadolinium (III) texaphyrin complex (2.5 mumol/kg) produced significant contrast enhancement of liver carcinomas in rabbits (n = 8). Thigh V2 carcinomas (n = 22) had selective (P < .05) enhancement, 5 mumol/kg. In rat fibrosarcomas (n = 4), 17 mumol Gd(III) texaphyrin complex produced significant enhancement up to 24 hours.


CONCLUSIONS
Gadolinium (III) texaphyrin complex appears to be an effective and safe MRI contrast agent.
Young
S W
SW
Department of Radiology, Stanford University School of Medicine.
Sidhu
M K
MK
Qing
F
F
Muller
H H
HH
Neuder
M
M
Zanassi
G
G
Mody
T D
TD
Hemmi
G
G
Dow
W
W
Mutch
J D
JD
D000818:Animals; D003287:Contrast Media / Q000633:toxicity; D005260:Female; D005682:Gadolinium / Q000633:toxicity; D008279:Magnetic Resonance Imaging; D008297:Male; D008665:Metalloporphyrins; D009374:Neoplasms, Experimental / Q000175:diagnosis; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D003287:Contrast Media; D008665:Metalloporphyrins; C437683:motexafin gadolinium; D005682:Gadolinium