A dual CT-MR dendrimer contrast agent as a surrogate marker for convection-enhanced delivery of intracerebral macromolecular therapeutic agents.
The feasibility of using Gd dendrimer-based macromolecules (Gd-G8 dendrimer) as a dual CT and MR contrast agent for monitoring convection-enhanced delivery of therapy in the brain is evaluated both in vitro and in vivo with optimal dosing established. In vitro CT attenuation values of the Gd-based agents ( approximately 6.0 HU mM(-1)) were approximately 1.6 times greater than iodine-based agents and the attenuation of the Gd-DTPA was comparable to Gd-G8 dendrimer. Visible enhancement was observed on both CT and MR using Gd-G8 dendrimer over a range of 23-78 mM; however, a concentration of at least 47 mM in Gd was required for adequate delineation of the injection site on both CT and MR. MR offers greater sensitivity than CT in estimating the volume of distribution (V(d)) and effectively quantified the agent's concentration and diffusion using T(1) mapping at much lower concentrations of Gd (<10 mM in [Gd]).
Regino
Celeste Aida S
CA
Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1088, USA. reginoc@mail.nih.gov
Walbridge
Stuart
S
Bernardo
Marcelino
M
Wong
Karen J
KJ
Johnson
Dennis
D
Lonser
Russell
R
Oldfield
Edward H
EH
Choyke
Peter L
PL
Brechbiel
Martin W
MW
D000818:Animals; D002531:Cerebellum / Q000000981:diagnostic imaging*; D003287:Contrast Media / Q000493:pharmacokinetics*; D050091:Dendrimers / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D005682:Gadolinium / Q000493:pharmacokinetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014057:Tomography, X-Ray Computed
D003287:Contrast Media; D050091:Dendrimers; D005682:Gadolinium