Distribution of gadomelitol in a human breast tumor model in mice.
The study evaluates the tumor distribution of the rapid clearance blood pool agent (RCBPA) gadomelitol, in a breast tumor model. Different techniques were used : (1) tissue gadolinium concentrations measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES), (2) whole body quantitative autoradiography using radiolabeled [153Gd] gadomelitol and (3) dynamic contrast-enhanced MRI with compartmental analysis. An accumulation of gadomelitol in tumors compared to muscle was observed 30 min and 3 h post injection (p.i.). Thirty minutes p.i., the gadomelitol tumor distribution evaluated by autoradiography showed a marked difference between the rim and the center, whereas both areas showed comparable concentrations after 3 h. Using dynamic contrast-enhanced MRI, three phases could be observed during the 1 hour observation period: (1) rapid tumor uptake within the first few minutes post-injection (2) a progressive increase in tumor signal enhancement over 10 min and (3) a steady-state phase. Average +/- SD (n=5) transendothelial permeability K(PS) and the fractional blood volume fBV were 12.2+/-1.6 microl/min(-1)/g and 5.4+/-0.2% respectively. Due to its slow extravasation and high tumor residence time, gadomelitol may potentially be useful to improve characterization between benign versus malignant tumors using dynamic MRI.
Corot
C
C
Guerbet Research, BP50400, 95943 Roissy CDG, France. Claire.corot@guerbet-group.com
Robert
P
P
Lancelot
E
E
Martinell
A
A
Santus
R
R
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003287:Contrast Media / Q000493:pharmacokinetics*; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C435266:contrast agent P792