Technetium-99m-Labeled N-(2-Hydroxypropyl) Methacrylamide Copolymers: Synthesis, Characterization, and in Vivo Biodistribution.

Purpose. 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-ω-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. [ABSTRACT FROM AUTHOR]