DEVELOPMENT OF NEW RENAL FUNCTION IMAGING AGENTS

现有的用于测量人类肾功能的放射性药物都没有准确地测量有效的肾脏血浆流量。这两种商用试剂的萃取效率仅为理想底物对氨基河马聚糖(PAH)的0.80倍和0.65倍。合成了一种新的亲水性五阴离子配合物[锶(羧甲基异氰化物)6]-5(TC-CAMI)，并在动物体内进行了评价。这种金属络合物的表面含有六个对称排列的羧酸基，它们可以作为有机阴离子受体的底物，提供这种原型试剂的管状分泌。在小鼠和兔体内的生物分布表明，该化合物具有与99mTC-MAG3和131I-河马聚糖相似的血药清除和分布，但在尿液中的清除速度较慢，并具有较高的残留肾脏活性。在狗身上，与已证实的肾小管分泌剂99mTC-MAG3和肾小球滤过剂(99mTC-DTPA)相比，99mTC-CAMI动态伽玛摄像显示出最快的血液清除速度，但排入尿液的速度略慢。这些实验和数据显示，丙磺舒与99mTC-竞争的血液清除最快，但排入尿液的速度略慢。这些实验和数据表明，丙磺舒与99mTC-CAMI竞争肾转运，表明该化合物作为一种肾小管分泌剂发挥作用，尽管不如“金标准”多环芳烃有效。拟议的商业应用：目前用于测量人体肾功能的放射性药物中，没有一种能准确测量有效的肾脏血浆流量。一种更高效的排泄剂将提高临床诊断的准确性，并通过有竞争力的定价降低成本。

None of the existing radiopharmaceuticals for measuring renal function in humans accurately measures effective renal plasma flow. The two commercially used agents exhibit extraction efficiencies of only .80 and .65 times that of the ideal substrate para-amino hippuran (PAH). A new prototype hydrophilic penta-anionic complex [Technetium (Carboxy- methyl-isocyanide)6]-5 (Tc-CAMI) has been synthesized and evaluated in animals. The surface of this metal complex contains six symmetrically arranged carboxylic acid groups that can act as substrates for the organic anion receptor affording tubular secretion of this prototype agent. Biodistribution in mice and rabbits showed this compound to have similar blood clearance and distribution to 99mTC-MAG3 and 131I-hippuran but a slower clearance into the urine and higher residual kidney activity. In dogs, dynamic gamma camera imaging of 99mTc-CAMI when compared with proven tubular secretion agent 99mTC-MAG3 and glomerular filtration agents (99mTC-DTPA) showed the fastest blood clearance but slightly slower excretion into the urine. These experiments and data that probenecid competes with 99mTc-showed the fastest blood clearance but slightly slower excretion into the urine. These experiments and data that probenecid competes with 99mTc-CAMI for renal transport indicates that this compound is functioning as a tubular secretion agent, although not as effective as the "gold standard" PAH. PROPOSED COMMERCIAL APPLICATIONS: None of the current radiopharmaceuticals for measuring renal function in humans accurately measures effective renal plasma flow. A more efficiently excrete renal agent would increase the accuracy of clinical diagnosis and lower the cost through competitive pricing.