PRECLINICAL EVALUATION OF GADOLINIUM(III) TEXAPHYRIN COMPLEX - A NEW PARAMAGNETIC CONTRAST AGENT FOR MAGNETIC-RESONANCE-IMAGING

RATIONALE AND OBJECTIVES. Gadolinium III texaphyrin (Gd[III] texaphyri n) 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 mu mol Gd(III) texaphyrin complex/kg body weight; 3 times per w eek for 3 weeks). Biodistribution and excretion studies were conducted in Sprague-Dawley rats; MRI studies were conducted in normal and tumo r-bearing rats and rabbits. RESULTS. Relaxivity values were as follows : r(1) = 19 (mu mol/L . sec)(-1) and r(2) = 22 (mu mol/L . sec)(-1). T he 21-day subchronic toxicity study revealed no abnormalities. The com pound is stable. Biodistribution demonstrated liver uptake. Magnetic r esonance imaging in normal (n = 34) and tumor-bearing (n = 4) rats and normal (n = 8) and tumor-bearing (n = 19) rabbits revealed: significa nt (P < .05) contrast enhancement of liver and kidney after 1-17 mu mo l/kg of Gd(III) texaphyrin complex. Gadolinium (III) texaphyrin comple x (2.5 mu mol/kg) produced significant contrast enhancement of liver c arcinomas in rabbits (n = 8). Thigh V2 carcinomas (n = 22) had selecti ve (P < .05) enhancement, 5 mu mol/kg. In rat fibrosarcomas (n = 4), 1 7 mu mol Gd(III) texaphyrin complex produced significant enhancement u p to 24 hours. CONCLUSIONS. Gadolinium (III) texaphyrin complex appear s to be an effective and safe MRI contrast agent.