A molecular CT blood pool contrast agent.
OBJECTIVE
A molecular-based computed tomographic (CT) contrast agent with prolonged vascular residence time is needed for vascular and tumor imaging. No particulate agents have reached clinical practice due to nonspecific macrophage activation. The authors' objective was to synthesize a water-soluble macromolecular agent.


METHODS
Dysprosium-DTPA-dextran was synthesized through activation of the hydroxyl units of dextran PM40 with allylbromine and subsequent reaction with amino ethanethiol to produce amino-terminated leashes. These leashes were then coupled to DTPA by means of the mixed anhydride method. Complexation of dysprosium by DTPA-dextran was achieved in an acidic solution of 0.2 M dysprosium chloride. One rabbit with a VX2 tumor was imaged with [Dy]DTPA-dextran (0.5 mL, 3.1 g, 1.15 mmol of dysprosium per kilogram). Transaxial scans were acquired through the liver and tumor for 45 minutes. A second healthy rabbit was imaged with Optiray-320 (6.0 mL, 5.0 mmol of iodine per kilogram) at 1-minute intervals for 10 minutes and again at 20 minutes.


RESULTS
Each dextran PM40 molecule (diameter, 8.8 nm) contained 95 [Dy]DTPA groups, increasing its average molecular weight from 40,500 to 101,537 g/mol. The baseline-corrected inferior vena cava (IVC) enhancement for [Dy]DTPA-dextran decreased, with an 8-minute half-time during the first 15 minutes followed by a nearly zero slope for the rest of the observation period. The IVC remained brighter than liver throughout the observation period. The solid portion of the tumor was enhanced by 5-10 CT numbers, rendering areas of necrosis more apparent. The baseline-corrected IVC curve for Optiray-320 also demonstrated two phases, with half-times of 2.5 and 45 minutes. The IVC became less dense than liver within 5-8 minutes.


CONCLUSIONS
[Dy]DTPA-dextran is water soluble and can be synthesized without intermolecular cross-linking to carry a high load of dysprosium. It provides blood pool enhancement characteristics with a long intravascular dwell time.
Vera
David R
DR
Department of Radiology, University of California, San Diego 92103-8756, USA.
Mattrey
Robert F
RF
D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000138:chemical synthesis*; D004419:Dysprosium / Q000097:blood; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging*; D008262:Macrophage Activation / Q000187:drug effects; D008970:Molecular Weight; D009942:Organometallic Compounds / Q000097:blood / Q000138:chemical synthesis*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis*; D011817:Rabbits; D014057:Tomography, X-Ray Computed; D014283:Triiodobenzoic Acids / Q000008:administration & dosage
D003287:Contrast Media; D009942:Organometallic Compounds; D014283:Triiodobenzoic Acids; D004419:Dysprosium; D004369:Pentetic Acid; C055865:dysprosium DTPA; C054871:ioversol