Radiolabeled Arg-Gly-Asp (RGD) peptide derivatives have immense potential for non-invasive monitoring of malignancies over-expressing integrin αv β3 receptors. Easy availability of suitable radiotracers would augment the utility of this class of molecular imaging agents. Toward this, the present article describes the development of an improved lyophilized kit for the routine clinical formulation of [99m Tc]Tc-complex of HYNIC-conjugated dimeric cyclic RGD peptide derive E-[c (RGDfK)]2 (E = glutamic acid, f = phenyl alanine, K = lysine) without using Sn2+ and systematic evaluation of its efficacy. Six batches of the kits were prepared and [99m Tc]Tc-HYNIC-E[c (RGDfK)]2 radiotracer was synthesized with high radiochemical purity (98.6 ± 0.5%) and specific activity (124.8 GBq/μmol maximum) using the kits. Biodistribution studies in C57BL/6 mice bearing melanoma tumor exhibited significant accumulation of the radiotracer in tumor (5.32 ± 0.56 %ID/g at 60 min p.i) and this uptake was found to be receptor-specific by blocking studies. Preliminary human clinical investigations carried out in ten breast cancer patients revealed high radiotracer uptake in the tumor along with good tumor-to-background contrast. The developed kit formulation showed an exceptionally high shelf-life of at least 18 months. These results demonstrated promising attributes of the developed kit formulation and warrant more extensive clinical investigations.

中文翻译：

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一种改进的试剂盒配方，用于 [99m Tc]Tc-HYNIC-E[c (RGDfK)]2 的一锅合成，用于癌症成像的常规临床应用

放射性标记的 Arg-Gly-Asp (RGD) 肽衍生物在非侵入性监测过度表达整合素 αv β3 受体的恶性肿瘤方面具有巨大潜力。容易获得合适的放射性示踪剂将增加这类分子显像剂的效用。为此，本文描述了改进的冻干试剂盒的开发，用于常规临床配方的 [99m Tc]Tc 复合物的 HYNIC 共轭二聚环 RGD 肽衍生 E-[c (RGDfK)]2（E = 谷氨酸, f = 苯丙氨酸, K = 赖氨酸) 不使用 Sn2+ 并对其功效进行系统评估。制备了六批试剂盒，并使用该试剂盒合成了具有高放射化学纯度 (98.6 ± 0.5%) 和比活性（最大 124.8 GBq/μmol）的 [99m Tc]Tc-HYNIC-E[c (RGDfK)]2 放射性示踪剂. 在携带黑色素瘤肿瘤的 C57BL/6 小鼠中进行的生物分布研究显示出放射性示踪剂在肿瘤中的显着积累（注射后 60 分钟时为 5.32 ± 0.56 %ID/g），并且通过阻断研究发现这种吸收是受体特异性的。在 10 名乳腺癌患者中进行的初步人体临床研究显示，肿瘤中放射性示踪剂的吸收率很高，并且肿瘤与背景的对比度良好。开发的试剂盒配方具有至少 18 个月的极高保质期。这些结果证明了开发的试剂盒配方的有希望的属性，并需要进行更广泛的临床研究。在 10 名乳腺癌患者中进行的初步人体临床研究显示，肿瘤中放射性示踪剂的吸收率很高，并且肿瘤与背景的对比度良好。开发的试剂盒配方具有至少 18 个月的极高保质期。这些结果证明了开发的试剂盒配方的有希望的属性，并需要进行更广泛的临床研究。在 10 名乳腺癌患者中进行的初步人体临床研究显示，肿瘤中放射性示踪剂的吸收率很高，并且肿瘤与背景的对比度良好。开发的试剂盒配方具有至少 18 个月的极高保质期。这些结果证明了开发的试剂盒配方的有希望的属性，并需要进行更广泛的临床研究。