Chakraborty Sudipta, Das Soumen, Chakravarty Rubel, Sarma Haladhar Dev, Vatsa Rakhee, Shukla Jaya, Mittal Bhagwant Rai, Dash Ashutosh
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.
Homi Bhabha National Institute, Mumbai, India.
J Labelled Comp Radiopharm. 2019 Oct;62(12):823-834. doi: 10.1002/jlcr.3786. Epub 2019 Aug 18.
Radiolabeled Arg-Gly-Asp (RGD) peptide derivatives have immense potential for non-invasive monitoring of malignancies overexpressing integrin α β receptors. Easy availability of suitable radiotracers would augment the utility of this class of molecular imaging agents. Towards this, the present article describes the development of an improved lyophilized kit for the routine clinical formulation of [ Tc]Tc complex of HYNIC-conjugated dimeric cyclic RGD peptide derivative E-[c(RGDfK)] (E = glutamic acid, f = phenyl alanine, K = lysine) without using Sn and systematic evaluation of its efficacy. Five batches of the kits were prepared, and [ Tc]Tc-HYNIC-E[c(RGDfK)] radiotracer was synthesized with high radiochemical purity (98.6 ± 0.5%) and specific activity (124.8 GBq/μmol) 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 also found to be receptor-specific by blocking studies. Preliminary human clinical investigations carried out in 10 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.
放射性标记的精氨酸-甘氨酸-天冬氨酸（RGD）肽衍生物在对过表达整联蛋白αβ受体的恶性肿瘤进行非侵入性监测方面具有巨大潜力。合适的放射性示踪剂易于获取将增加这类分子成像剂的实用性。为此，本文描述了一种改进的冻干试剂盒的开发，该试剂盒用于常规临床配制HYNIC偶联的二聚体环状RGD肽衍生物E-[c(RGDfK)]（E = 谷氨酸，f = 苯丙氨酸，K = 赖氨酸）的[ Tc]Tc配合物，且无需使用锡，并对其功效进行了系统评估。制备了五批试剂盒，并使用这些试剂盒合成了具有高放射化学纯度（98.6±0.5%）和比活度（124.8 GBq/μmol）的[ Tc]Tc-HYNIC-E[c(RGDfK)]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表明，放射性示踪剂在肿瘤中显著蓄积（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摄取也是受体特异性的。在10例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摄取高，且肿瘤与背景对比度良好。所开发的试剂盒制剂显示出至少18个月异常高的保质期。这些结果证明了所开发的试剂盒制剂具有良好的特性，值得进行更广泛的临床研究。
