Radiopharmacological evaluation in dogs of a new renal function agent.

S Verdera, J J Lòpez, R Tagle, F Garcia, G Fernandez, M Keuchkerian, C Heuguerot, A G Jones, J F Kronauge
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Abstract

The hydrophilic penta-anionic complex [Technetium (Carboxymethylisocyanide)6]-5, [Tc(CNCH2COO-)6]-5 (Tc-CAMI) was synthesized to evaluate its potential as a renal function imaging agent. The compound contains six distally arranged carboxyl groups that can act as substrates for the organic acid receptor of the renal cell to effect tubular secretion of this agent. Dynamic gamma-camera imaging of 99mTc-CAMI was performed in normal dogs to compare its bio-distribution and pharmacokinetics with those of proven tubular secretion (99mTc-MAG3) and globular filtration (99mTc-DTPA) agents. The relative difference between the observed mean renal transit times (MRTT) of 99mTc-CAMI and 99mTc-MAG3 was 0.15 compared with 1.24 for 99mTc-CAMI and 99mTc-DTPA. Pathological models of obstructive uropathy, renal arterial stenosis and renal denervation were produced in the same animals to demonstrate the diagnostic potential of the agent. These experiments and data showing that probenecid competes with 99mTc-CAMI for renal transport indicate that this compound functions as a tubular secretion agent and may be useful for monitoring renal function in various disease states.

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一种新型肾功能药物在犬体内的放射药理学评价。
合成了亲水五阴离子配合物[Technetium (Carboxymethylisocyanide)6]-5, [Tc(CNCH2COO-)6]-5 (Tc- cami),以评价其作为肾功能显像剂的潜力。该化合物含有6个远端排列的羧基,可作为肾细胞有机酸受体的底物,影响该药物的小管分泌。对正常犬进行99mTc-CAMI的动态伽马相机成像,比较其与已证实的小管分泌剂(99mTc-MAG3)和球状滤过剂(99mTc-DTPA)的生物分布和药代动力学。99mTc-CAMI和99mTc-MAG3观察到的平均肾传递时间(MRTT)的相对差异为0.15,而99mTc-CAMI和99mTc-DTPA的相对差异为1.24。在相同的动物中制作了梗阻性尿病、肾动脉狭窄和肾去神经支配的病理模型,以证明该药物的诊断潜力。这些实验和数据表明,probenecid与99mTc-CAMI竞争肾脏运输,表明该化合物作为小管分泌剂发挥作用,可能有助于监测各种疾病状态下的肾功能。
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