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Development of poly(ethylene glycol)-coated vesicles as cardiovascular imaging agents for nuclear medicine

University of British Columbia

The development and use of poly(ethylene glycol) (PEG)-coated vesicles as nuclear medicine blood pool imaging agents is described from the initial synthesis of chelator, through labeling of vesicles with technetium-99m ([sup 99m]Tc), to the final testing in a human subject. Using hexamethyl-propyleneamine oxime (HM-PAO) as the chelate molecule, a novel pH gradient method was developed for the rapid, robust and reproducible labeling of pre-formed vesicles with labeling efficiencies greater than 90%. In vivo (pyrogen and hemodynamic studies in rabbits) and in vitro (CH50 hemolytic assay) studies were conducted to determine the safety and tolerability of PEG-coated vesicles. Results showed that there was no significant alterations in hemodynamic parameters or activation of the complement system. Also, vesicles and the vesicle preparation procedure were found to be non-pyrogenic. In vivo studies in rabbits revealed that vesicles with 4.5 mol% PEG, exhibited both lipid dose-dependent and -independent circulation half-lives contrary to published data. A circulation half-life of ~ 15 hours was achieved at lipid dose greater than ~1.0 μmol of total lipid/kg of body weight. Based on these in vitro studies and in vivo rabbit results, a vesicle based kit was developed and tested in a human subject. The left ventricular ejection fraction (LVEF) was calculated using labeled vesicles and was compared to the LVEF calculated with the current standard of radiolabeled autologous red blood cells (RBCs). The values were found to be similar (69% for RBCs and 73% for vesicles) indicating that PEG-coated vesicles labeled with [sup 99m]Tc are a suitable alternative to RBCs for cardiovascular imaging.

Thesis/Dissertation

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2009-04-30

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http://hdl.handle.net/2429/7732

Biochemistry and Molecular Biology

University of British Columbia

UBCV

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