Synthetic copolymer kit for radionuclide blood-pool imaging.
A synthetic blood pool imaging agent labeled with 99mTc is reported.


METHODS
The agent, methoxypolyethylene glycol-poly-L-lysyl-diethylenetriaminepentaacetate monoamide was synthesized from a covalent graft copolymer of methoxypolyethylene glycol succinate (molecular weight 5.1 kD) and poly-L-lysine (molecular weight average 35.6 kD) with subsequent modification of the product with diethylenetriamineacetyl residues. The polymer was formulated into a kit that contained Sn(II) and sodium acetate for radiolabeling with 99mTc. Biodistribution studies were performed in rats. Blood-pool imaging and blood clearance determination was carried out in rabbits and in a rhesus monkey.


RESULTS
The 99mTc-labeled agent [specific activity greater than 3.7 GBq/mg; radiochemical purity more than 98% by thin-layer and high-performance liquid chromatography (HPLC)] demonstrated remarkable stability in solution (pH 5.5-6.5) with no radioactive products of degradation detectable by HPLC even at 24 hr postlabeling. The agent exhibited prolonged circulation in the blood with a half-life of 31.5 hr in rabbits. Biodistribution in rats showed a lack of substantial accumulation of the agent in the reticuloendothelial system. Sequential acquisitions were performed in a rhesus monkey. The 99mTc-labeled polymer kit was compared with the 99mTc-red blood cells (RBCs) labeled in vitro. Both methods produced similar heart-to-lung ratios. The ratios remained essentially unchanged for up to 15 hr postinjection.


CONCLUSIONS
The 99mTc-labeled methoxypolyethylene glycol-poly-L-lysyl-diethylenetriamine pentaacetate monoamide is an attractive alternative to radiolabeled RBCs for blood pool imaging applications.
Department of Radiology, Massachusetts General Hospital, Boston.
A A
AA
Bogdanov
R J
RJ
Callahan
R A
RA
Wilkinson
C
C
Martin
J A
JA
Cameron
A J
AJ
Fischman
T J
TJ
Brady
R
R
Weissleder
D000818:Animals; D015637:Gated Blood-Pool Imaging; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011933:Reagent Kits, Diagnostic; D016284:Technetium Tc 99m Pentetate / Q000031:analogs & derivatives*; D014018:Tissue Distribution
D011933:Reagent Kits, Diagnostic; C090366:technetium Tc 99m methoxypolyethylene glycol-polylysyl-DTPA monoamide; D016284:Technetium Tc 99m Pentetate