Evaluation of [Gd(Bz-TTDA)]2- as a potential contrast agent in MR imaging of the hepatobiliary system: an animal study.
OBJECTIVE
To evaluate the potential of a new lipophilic paramagnetic complex [Gd(Bz-TTDA)]2- [(4s)-4-benzyl-3,6,10-tri(carboxymethyl)-3,6,10-triazadodecandioic acid]2- designed for use as a hepatobiliary MR contrast agent.


METHODS
MR imaging studies for normal and hepatocellular carcinoma (HCC) rat models were performed using a 1.5-T scanner. Sequential multislice T1-weighted turbo field echo (TFE) (TR/TE/flip angle: 15 msec/6.1 msec/25 degrees) coronal images of normal rats were obtained before and after intravenous injections of 0.1 mmol/kg [Gd(Bz-TTDA)]2- in study groups (N = 12) or 0.1 mmol/kg gadopentate dimeglumine (Gd-DTPA)2- in control groups (N = 12). Similar protocols of MR imaging with additional T2-weighted images were used for the rats with implanted HCC in both study and control groups (N = 12, in each group). MR images were analyzed to evaluate the time-enhancement change (% increase of signal-to-noise ratio [SI/N]) in normal liver, renal cortex, renal medulla, and tumors. The liver-lesion contrast-to-noise ratios (CNR) were also evaluated in study and control groups. The rats were killed immediately after the last MR scan to undergo autopsy and histopathologic observation. The acute toxicity test (medial lethal dose, LD50) in mice was also done.


RESULTS
The liver enhancement in normal rats reached a plateau 5-50 minutes after injection of [Gd(Bz-TTDA)]2-, maintained for three hours, then gradually declined. Intensity of enhancement in liver, renal cortex, and medulla after injection of [Gd(Bz-TTDA)]2- was significantly higher than with Gd-DTPA. The efficacy of tumor characterization with injection of [Gd(Bz-TTDA)]2- was similar to that of Gd-DTPA at the early dynamic phase of the contrast study. However, the liver-lesion CNRs were significantly higher in the study group in the later phase, when tumor enhancement decreased and liver enhancement persisted. The dose of LD50 in acute toxicity test of [Gd(Bz-TTDA)]2- in mice was 7.5 mmol/kg.


CONCLUSIONS
The preliminary results in this animal study indicated that [Gd(Bz-TTDA)]2- has the potential of becoming a reliable liver MR contrast agent.
Hsu
Jui-Sheng
JS
Department of Medical Imaging, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jaw
Twei-Shiun
TS
Liu
Gin-Chung
GC
Wang
Yun-Ming
YM
Chen
Shih-Hsien
SH
Kuo
Yu-Ting
YT
Jao
Jo-Chi
JC
Li
Chun-Wei
CW
Tsai
Kun-Bow
KB
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis*; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D004195:Disease Models, Animal; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D008113:Liver Neoplasms / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity
D003287:Contrast Media; D009942:Organometallic Compounds; C496019:gadolinium ((4S)-4-benzyl-3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid)2