Development of a novel ⁶⁸Ga-dextran carboxylate derivative for blood pool imaging

Abstract

To develop a possible PET blood pool imaging agent, a series 68Ga-dextran carboxylate derivatives were prepared. Dextran carboxylates with different degree of oxidations (DO) were prepared through stepwise dextran oxidation using NaIO4 and CH3COOOH. The products were characterized by FT-IR and GPC, followed by solubility and toxicity tests on Hella cells (viability=98.6, 97.4 and 95.6% for 3 dextran carboxylates with DOs: 8.3, 24.6 and 39.8%, respectively. The products were labeled with 68Ga (radiochemical purity>98%; ITLC) followed by stability tests in final solution as well as in presence of cycteine and human serum. Two stable tracers (DOs; 24.6 and 39.8%) were adminstered intravenously into wild type rat tail vein separately demonstrating suitable retention in circulation as expected from blood pool imaging agents. Liver and spleen also contained activities. The major excretion was through urinary pathway esp. for derivative with DO. 39.8%. Unlike 68Ga-dextran, lungs showed lower uptake. The dextran carboxylate with the highest 39.8% showed the best characteristics for a blood pool agent, though more studies including PET imaging in larger mammals are required.

68Ga-Labeled Maleimide for Blood Pool and Lymph PET Imaging through Covalent Bonding to Serum Albumin In Vivo

“… 9 HSA is a good alternative to RBCs, but the requirement of in vitro labeling may face the problems of immunogenicity, renal elimination, and unstable biosafety activities caused by the complicated purification steps. Besides, there are problems such as poor stability, 10 high liver background uptake, 11 and low radiochemistry yield, 12 when albumin-based radiopharmaceuticals are applied to the blood pool, lymphatic detection, and other aspects. To overcome the shortcomings of in vitro labeling of albumin, radiolabeled Evans Blue (EB) dye analogues ([ 18 F]AlF-NEB, [ 64 Cu]Cu-NEB, and [ 68 Ga]Ga-NEB) 13 , 14 and radioiodinated 4-( p -iodophenyl) butyric acid ([ 131 I]IBA) 15 were developed for in vivo labeling of the endogenous albumin.…”