Chervu L R, Sundoro B M, Blaufox M D
J Nucl Med. 1984 Oct;25(10):1111-5.
A renal agent labeled with Tc-99m and quantitatively secreted by the tubules has been sought for many years. To meet this need, a PAH analog (PAHIDA), has been synthesized by the coupling of p-aminohippuric acid with nitrilotriacetic acid anhydride, using Sn(II) reduction. This yields a stable complex with Tc-99m at a pH of 5.8. The purity and stability of the Tc-99m complex have been established by ITLC and high performance liquid chromatography (HPLC). Urinary excretions of the Tc-99m PAHIDA and I-131 hippurate, determined in mice and rats at different time intervals, are similar. The new compound is clearly excreted but its total clearance is lower than that of hippurate as a result of high protein binding. Rat urine analysis by ITLC and HPLC suggests that the agent excreted is similar to the complex administered to the animals. The Tc-99m-labeled agent is rapidly excreted in urine with no significant extrarenal pathway, thus providing excellent renal scintigrams in a rabbit model. The Tc-99m PAHIDA contains the R-CO-NH-CH2-COOH grouping, analogous to that in hippurate, and consequently may provide the substrate specificity for renal excretion of this new class of agents labeled with technetium-99m.
多年来一直在寻找一种用锝-99m标记并由肾小管定量分泌的肾显像剂。为满足这一需求，已通过对氨基马尿酸与次氮基三乙酸酐偶联，并采用二价锡还原法合成了一种对氨基马尿酸类似物（PAHIDA）。这在pH值为5.8时会与锝-99m形成稳定的络合物。锝-99m络合物的纯度和稳定性已通过离子薄层层析（ITLC）和高效液相色谱法（HPLC）得以确定。在不同时间间隔对小鼠和大鼠测定的锝-99m PAHIDA和碘-131马尿酸盐的尿排泄情况相似。新化合物明显可被排泄，但由于高蛋白结合率，其总清除率低于马尿酸盐。通过ITLC和HPLC对大鼠尿液分析表明，排泄出的试剂与给予动物的络合物相似。用锝-99m标记的试剂迅速经尿液排泄，无明显肾外途径，因此在兔模型中可提供优质的肾闪烁图。锝-99m PAHIDA含有与马尿酸盐中类似的R-CO-NH-CH2-COOH基团，因此可能为这类用锝-99m标记的新型试剂的肾排泄提供底物特异性。
