Technetium-99m-labeled N-(2-hydroxypropyl) methacrylamide copolymers:: Synthesis, characterization, and in vivo biodistribution
Technetium-99m-labeled N-(2-hydroxypropyl) methacrylamide copolymers:: Synthesis, characterization, and in vivo biodistribution
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DOI：
10.1023/b:pham.0000033001.49737.b7
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发表时间：
2004-07-01
影响因子：
3.7
通讯作者：
Line, BR
中科院分区：
文献类型：
--
作者：
Mitra, A;Nan, A;Line, BR
目的.目的合成新型99 m锝（Tc-99 m）标记的N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物，并研究电荷和分子量对其在SCID小鼠体内分布的影响。通过自由基沉淀共聚合法合成了含有Tc-99 m螯合共聚单体、带有N-ω-双（2-吡啶甲基）-L-赖氨酸（DPK）的负电性和中性7-kDa、21-kDa和70-kDa HPMA共聚物。共聚物通过Tc-99 m三羰基螯合到带有PK的共聚单体上进行标记。通过侧链含量、分子量、分子量分布、放射化学纯度和标记稳定性对其进行表征。在SCID小鼠静脉注射后的前90分钟和24小时获得闪烁图像。在24 h时，通过尸检组织计数确定器官放射性。Tc-99 m标记的HPMA共聚物在24小时的挑战与半胱氨酸和组氨酸显示大于90%的稳定性。闪烁图像和尸检数据显示，带负电荷的共聚物从体内消除的速度明显快于中性共聚物的大小依赖性的方式。为了促进临床放射性成像，可以通过将带有DPK的共聚单体掺入HPMA主链中来实现Tc-99 m的稳定螯合。电负性和中性Tc-99 m标记的HPMA共聚物的7，21，和70 kDa的器官在SCID小鼠的生物分布显示出显着的变化。Tc-99 m标记的HPMA共聚物可用作诊断剂，并可用于基于这些共聚物的递送系统的药代动力学研究。
Purpose. To synthesize novel technetium-99m (Tc-99m)-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 Tc-99m chelating comonomer, bearing N-omega-bis(2-pyridylmethyl)-L-lysine (DPK), were synthesized by free-radical precipitation copolymerization. The copolymers were labeled via Tc-99m 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. Tc-99m-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 Tc-99m may be achieved by incorporation of a DPK-bearing comonomer into the HPMA backbone. Electronegative and neutral Tc-99m-labeled HPMA copolymers of 7, 21, and 70 kDa show significant variation in organ biodistribution in SCID mice. Tc-99m-labeled HPMA copolymers could be used as diagnostic agents and to study pharmacokinetics of delivery systems based on these copolymers.