A new polysaccharide macromolecular contrast agent for MR imaging: biodistribution and imaging characteristics.
The aims of this study were to characterize certain physicochemical, pharmacokinetic, and enhancement properties of a new macromolecular contrast agent, carboxymethyl hydroxyethyl starch-(Gd-DO3A)(35) [CMHES-(Gd-DO3A)(35)], consisting of a polysaccharide backbone covalently derivatized with multiple macrocyclic chelating groups for gadolinium. CMHES-(Gd-DO3A)(35) has an average molecular weight of 72 kD and a plasma half-time of 8.4 hours. T1 and T2 relaxivities are 14.1 +/- 0.1 L mmol(-1) * sec(-1) and 17.8 +/- 0.9 L mmol(-1) * sec(-1), respectively, for each gadolinium ion measured at 39 degrees C and 20 Mhz; this T1 relaxivity is more than 4 times that of gadopentetate. Seven days after intravenous administration only relatively small amounts of gadolinium could be detected in blood or other tissues of rats. The compound was well tolerated in diagnostic dosages by all experimental animals. Magnetic resonance angiography performed within 1 hour of CMHES-(Gd-DO3A)(35) administration showed a near-constant and strong enhancement of blood in arteries and veins. Analysis of dynamic enhancement patterns of experimental tumors (MAT-LyLu prostate cancer implanted in rats) following intravenous CMHES-(Gd-DO3A)(35) administration yielded quantitative estimates of tumor plasma volume and microvessel permeability; the demonstrated hyperpermeability of tumor microvessels was easily distinguished from the absence of measurable microvascular permeability in non-neoplastic soft tissues.
Helbich
T H
TH
Contrast Media Laboratory, Department of Radiology, University of California-San Francisco, San Francisco, California 94143, USA.
Gossman
A
A
Mareski
P A
PA
Radüchel
B
B
Roberts
T P
TP
Shames
D M
DM
Mühler
M
M
Turetschek
K
K
Brasch
R C
RC
D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D005260:Female; D005682:Gadolinium / Q000737:chemistry / Q000493:pharmacokinetics*; D006895:Hydroxyethyl Starch Derivatives; D007089:Image Enhancement; D018810:Magnetic Resonance Angiography / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009942:Organometallic Compounds; D011467:Prostate / Q000098:blood supply / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D051381:Rats; D012680:Sensitivity and Specificity; D012984:Software; D014018:Tissue Distribution
D003287:Contrast Media; D006895:Hydroxyethyl Starch Derivatives; D009942:Organometallic Compounds; C411945:carboxymethyl hydroxyethyl starch-(Gd-DO3A)(35); D005682:Gadolinium