Evaluation of rHA labeled with Gd-DTPA for blood pool imaging and targeted contrast delivery.
A new contrast agent was developed by linking Gd-DTPA chelate to recombinant human albumin in the laboratory. The molar relaxivity of the new agent was tested in aqueous solution at B(0) 1.5 T and temperature 20 degrees C. The soluble compound had a higher molar longitudinal relaxivity and molar transverse relaxivity in water (r(1) = 7.2 s(-1) mM(-1), r(2) = 18.4 s(-1) mM(-1)) than those measured for Gd-DTPA solution (r(1) = 3.5 s(-1) mM(-1), r(2) = 5.5 s(-1) mM(-1)). The performance of the compound as a blood pool agent was investigated with soluble and microparticulate forms of the compound and comparisons were made with Gd-DTPA and the polymeric blood-pool agent, Gadomer. T(1)-weighted imaging experiments show that the soluble compound acts as a highly effective blood pool agent with hyperintensity in the vasculature persisting beyond 2 h post administration, compared with free Gd-DTPA, which was cleared from the blood pool after approximately 10 min. The clearance kinetics of the new agents were examined, due to the incomplete elimination within 14 days post injection; both rHA labeled compounds are probably not suitable for development as routine blood pool contrast media. However, with free sites on the Gd-loaded rHA molecule, there are possibilities for binding the agent to antibodies in the laboratory, which was demonstrated, and thus there exist potential applications for in vivo molecular imaging with this agent.
Unit of Academic Radiology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK. j.m.wild@sheffield.ac.uk
Jim M
JM
Wild
John
J
Woodrow
Edwin J R
EJ
van Beek
Bernd
B
Misselwitz
Richard
R
Johnson
D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D019786:Gadolinium DTPA / Q000097:blood / Q000378:metabolism*; D015637:Gated Blood-Pool Imaging / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*; D012995:Solubility; D013194:Staining and Labeling / Q000379:methods*
D003287:Contrast Media; D011994:Recombinant Proteins; D012709:Serum Albumin; D019786:Gadolinium DTPA