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.
Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland 21201, USA.
Amitava
A
Mitra
Anjan
A
Nan
Hamidreza
H
Ghandehari
Edwina
E
McNeill
Justin
J
Mulholland
Bruce R
BR
Line
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