Evaluation of CH3-DTPA-Gd (NMS60) as a new MR contrast agent: early phase II study in brain tumors and dual dynamic contrast-enhanced imaging.
OBJECTIVE
A newly developed contrast material, CH3-DTPA-Gd (NMS60), a trimer containing 3 Gd(3+) atoms per molecule, has been shown to offer greater enhancement and longer vascular retention than gadopentetate dimeglumine (Gd-DTPA) in animals. We report on our early phase II study on NMS60 in brain tumor patients together with supplementary investigations.


METHODS
The longitudinal relaxation rate (R(1)=1/T(1)) and the transverse relaxation rate (R(2)*=1/T(2)*) of NMS60 and Gd-DTPA were determined at 20 degrees C in water at 1.5 T. An NMS60 dose of 0.1 or 0.2 mmol (Gd)/kg was randomly assigned and administered to 10 patients (five women, five men; mean age: 49 years) with brain tumors. Safety and contrast-enhancing ability of NMS60 were evaluated. Dual dynamic contrast-enhanced T(1) and R(2)* studies (DUCE imaging) were also carried out in two patients.


RESULTS
Regarding the relaxivity per Gd, R(1) and R(2)* of NMS60 were 9.5 and 11.0 (mmol/L x s)(-1), respectively, compared to 4.8 and 7.2 (mmol/L x s)(-1) for Gd-DTPA. Although a transient slight increase of alanine aminotransferase was observed in one case, no other adverse reactions were observed after administration of NMS60. Contrast enhancement by NMS60 was excellent at both concentrations, and when tumor detectability was assessed with a five-point scale, the diagnostic usefulness was 4 or higher in all cases. In DUCE imaging, NMS60 appeared to show high signal intensity, when compared with the data obtained separately for Gd-DTPA.


CONCLUSIONS
NMS60 had a high contrasting effect and little toxicity, and is expected to be clinically useful.
Ito
Masato
M
Department of Radiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8602, Japan. masato.ito@gmail.com
Ogino
Hiroyuki
H
Oshima
Hidekazu
H
Shiraki
Norio
N
Shibamoto
Yuta
Y
Kasai
Harumasa
H
Mase
Mitsuhito
M
Kawamura
Yasutaka
Y
Miyati
Tosiaki
T
D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000175:diagnosis*; D003287:Contrast Media; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009942:Organometallic Compounds; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D003287:Contrast Media; C403805:NMS60; D009942:Organometallic Compounds