99mTc(CO)3-nitrilotriacetic acid: a new renal radiopharmaceutical showing pharmacokinetic properties in rats comparable to those of 131I-OIH.
99mTc(CO)3-nitrilotriacetic acid: a new renal radiopharmaceutical showing pharmacokinetic properties in rats comparable to those of 131I-OIH.
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DOI：
10.2967/jnumed.108.058768
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Taylor AT
中科院分区：
文献类型：
--
作者：
Lipowska M;Marzilli LG;Taylor AT
为了开发一种99 mTc肾示踪剂，其测量有效肾血浆流量的能力与临床金标准131 I-O-碘马尿酸盐（131 I-OIH）相当，并上级99 mTc O-巯基乙酰基三甘氨酸（99 mTcO-MAG 3），其清除率仅为131 I-OIH的50-60%，我们研究了99 mTc三羰基次氮基三乙酸（Na 2 [99 mTc（CO）3（NTA）]）。这种基于氨基聚羧酸盐配体的放射性药物形成为单一物质，并且具有有利于管状运输的悬挂羧酸盐基团。通过使用市售NTA和IsoLink试剂盒制备Na 2 [99 mTc（CO）3（NTA）]，并通过高效液相色谱法分离。评估Na 2 [99 mTc（CO）3（NTA）]在等渗盐水中24小时的稳定性，并通过在37 °C下在0.1 M半胱氨酸和组氨酸中孵育4小时进一步评估。用~（99）mTc（CO）_3（NTA）与~（131）I-OIH共注射，观察注射后10 min、60 min（A组）和60 min（B组）Na_2 [~（99）mTc（CO）_3（NTA）]在大鼠肾组织中的分布。在2只正常Sprague-Dawley大鼠中进行了清除率和提取分数研究，并通过高效液相色谱法分析了另外2只正常大鼠的尿液和血浆中的代谢产物。Na 2 [99 mTc（CO）3（NTA）]的放射化学纯度大于99%，配合物在生理pH下稳定24 h，挑战实验显示无降解。在正常大鼠中，10 min和60 min时尿液中的剂量百分比分别为131 I-OIH的108 ± 9%和101 ± 5%;证实了最小的肝脏和胃肠道活动。B组Na 2 [99 mTc（CO）3（NTA）]在血中滞留较好，排入肠道的量较131 I-OIH少（P < 0.01）。Na 2 [99 mTc（CO）3（NTA）]和131 I-OIH的血浆清除率相当，但Na 2 [99 mTc（CO）3（NTA）]的提取分数为93.5 ± 3.8%，而131 I-OIH的提取分数为67.9 ± 6.1%。Na 2 [99 mTc（CO）3（NTA）]的血浆蛋白结合率平均为67 ± 7%，红细胞摄取率为7 ± 2%。Na 2 [99 mTc（CO）3（NTA）]是稳定的，作为单一物质存在，在大鼠中具有与131 I-OIH相当的药效学特性。
To develop a 99mTc renal tracer with a capacity to measure effective renal plasma flow comparable to that of the clinical gold standard 131I-o-iodohippurate (131I-OIH) and superior to that of 99mTcO-mercaptoacetyltriglycine (99mTcO-MAG3), which has a clearance only 50–60% that of 131I-OIH, we investigated 99mTc tricarbonyl nitrilotriacetic acid (Na2[99mTc(CO)3(NTA)]). This radiopharmaceutical, which is based on an aminopolycarboxylate ligand, is formed as a single species and has a dangling carboxylate group favoring tubular transport. Na2[99mTc(CO)3(NTA)] was prepared by using commercially available NTA and an IsoLink kit and isolated by high-performance liquid chromatography. The stability of Na2[99mTc(CO)3(NTA)] in isotonic saline was assessed for 24 h and was further evaluated by incubation in 0.1 M cysteine and histidine for 4 h at 37 °C. The biodistribution of Na2[99mTc(CO)3(NTA)], coinjected with 131I-OIH as an internal control, was evaluated in 5 normal Sprague-Dawley rats at 10 min, 5 normal Sprague-Dawley rats at 60 min (group A) and 6 rats with renal pedicle ligation at 60 min (group B) after injection. Clearance and extraction fraction studies were conducted in 2 normal Sprague-Dawley rats, and urine and plasma from 2 additional normal rats each were analyzed for metabolites by high-performance liquid chromatography. The radiochemical purity of Na2[99mTc(CO)3(NTA)] was greater than 99 %, the complex was stable for 24 h at physiological pH, and the challenge experiments showed no degradation. In normal rats, the percent dose in the urine at 10 and 60 min was 108 ± 9 % and 101 ± 5 %, respectively, that of 131I-OIH; minimal hepatic and gastrointestinal activity was demonstrated. In group B rats, Na2[99mTc(CO)3(NTA)] was better retained in the blood and had less excretion into the bowel than did 131I-OIH (P < 0.01). The plasma clearances of Na2[99mTc(CO)3(NTA)] and 131I-OIH were comparable, but the extraction fraction of Na2[99mTc(CO)3(NTA)] was 93.5 ± 3.8%, compared to 67.9 ± 6.1% for 131I-OIH. Plasma protein binding of Na2[99mTc(CO)3(NTA)] averaged 67 ± 7%, and red cell uptake was 7 ± 2%. Na2[99mTc(CO)3(NTA)] is stable, exists as a single species, and has pharmacodynamic properties in rats comparable to those of 131I-OIH.
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影响因子：
3.1
作者：
He, Haiyang;Lipowska, Malgorzata;Taylor, Andrew T.
通讯作者：
Taylor, Andrew T.
影响因子：
15
作者：
Alberto, R;Schibli, R;Kaden, TA
通讯作者：
Kaden, TA
影响因子：
4.6
作者：
Hansen, L;Lipowska, M;Marzilli, LG
通讯作者：
Marzilli, LG
影响因子：
4.9
作者：
ESHIMA, D;TAYLOR, A
通讯作者：
TAYLOR, A
影响因子：
1.8
作者：
Rattat, D;Verbruggen, A;Alberto, R
通讯作者：
Alberto, R