Technetium-99m-Labeled N-(2-hydroxypropyl) methacrylamide copolymers: synthesis, characterization, and in vivo biodistribution.
OBJECTIVE
To synthesize novel technetium-99m (99mTc)-labeled N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers and characterize the effect of charge and molecular weight on their biodistribution in SCID mice.


METHODS
Electronegative and neutral 7-kDa, 21-kDa, and 70-kDa HPMA copolymers containing a 99mTc chelating comonomer, bearing N-omega-bis(2-pyridylmethyl)-L-lysine (DPK), were synthesized by free-radical precipitation copolymerization. The copolymers were labeled via 99mTc tricarbonyl chelation to DPK-bearing comonomer. They were characterized by side-chain content, molecular weight, molecular weight distribution, radiochemical purity, and labeling stability. Scintigraphic images were obtained during the first 90 min and at 24 h postintravenous injection in SCID mice. At 24 h, organ radioactivity was determined from necropsy tissue counting.


RESULTS
99mTc-labeled HPMA copolymers showed greater than 90% stability over a 24-h challenge with cysteine and histidine. Scintigraphic images and the necropsy data showed that the negatively charged copolymers were eliminated from the body significantly faster than the neutral copolymers in a size-dependent manner.


CONCLUSIONS
To facilitate clinical scintigraphic imaging, stable chelation of 99mTc may be achieved by incorporation of a DPK-bearing comonomer into the HPMA backbone. Electronegative and neutral 99mTc-labeled HPMA copolymers of 7, 21, and 70 kDa show significant variation in organ biodistribution in SCID mice. 99mTc-labeled HPMA copolymers could be used as diagnostic agents and to study pharmacokinetics of delivery systems based on these copolymers.
Mitra
Amitava
A
Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland 21201, USA.
Nan
Anjan
A
Ghandehari
Hamidreza
H
McNeill
Edwina
E
Mulholland
Justin
J
Line
Bruce R
BR
D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008970:Molecular Weight; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000178:Acrylamides; D004337:Drug Carriers; D011108:Polymers; D019275:Radiopharmaceuticals; D013667:Technetium; C032976:N-(2-hydroxypropyl)methacrylamide