Das Tapas, Banerjee Sharmila, Shinto Ajit, Kamaleshwaran K K, Sarma H D
Isotope Applications and Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
Curr Radiopharm. 2014;7(1):12-9. doi: 10.2174/1874471007666140605100812.
Patient dose of (177)Lu-DOTA-TATE, used for providing radiotherapeutic treatment to the patients suffering from cancers of neuroendocrine origin, could be prepared at the hospital radiopharmacy either 'in-situ' or by using freezedried kits. The objective of the present work is to formulate and evaluate a single vial freeze-dried DOTA-TATE kit, which is capable of producing up to 7.4 GBq (200 mCi) dose of (177)Lu-DOTA-TATE and to compare the two methodologies presently used for the preparation of the agent.
Freeze-dried DOTA-TATE kits, comprising a lyophilized mixture of DOTA-TATE, gentisic acid and ammonium acetate, were prepared and used for the formulation of patient doses of (177)Lu-DOTA-TATE. The kits were subjected to detailed radiochemical evaluation and the shelf-life of the kits was determined. The pharmacokinetic behavior of the agent was studied in normal Wistar rats. These kits were utilized for treating the patients suffering from various types of neuroendocrine cancers.
The freeze-dried kits were used for the preparation of up to 7.4 GBq (200 mCi) therapeutic doses of (177)Lu- DOTA-TATE with a radiochemical purity of >99% and were found to have sufficiently long shelf-life. Biological studies carried out in normal Wistar rats exhibited no significant accumulation of activity in any of the vital organs/tissue except in kidneys and non-accumulated activity showed major renal clearance. Clinical studies carried out in cancer patients exhibited accumulation of activity in the cancerous lesions and metastatic sites.
The kit was useful for the convenient preparation of therapeutic dose of (177)Lu-DOTA-TATE, suitable for human administration. The use of kit is expected to reduce the batch failure and radiation exposure to the working personnel.
用于为神经内分泌源性癌症患者提供放射治疗的（177）镥-多胺基多羧基配体-奥曲肽（（177）Lu-DOTA-TATE）患者剂量，可在医院放射性药房通过“原位”法或使用冻干试剂盒制备。本研究的目的是配制并评估一种单瓶冻干DOTA-TATE试剂盒，该试剂盒能够制备高达7.4 GBq（200 mCi）剂量的（177）Lu-DOTA-TATE，并比较目前用于制备该制剂的两种方法。
制备了包含DOTA-TATE、龙胆酸和醋酸铵冻干混合物的冻干DOTA-TATE试剂盒，并用于配制（177）Lu-DOTA-TATE患者剂量。对试剂盒进行了详细的放射化学评估，并确定了试剂盒的保质期。在正常Wistar大鼠中研究了该制剂的药代动力学行为。这些试剂盒用于治疗患有各种类型神经内分泌癌的患者。
冻干试剂盒用于制备高达7.4 GBq（200 mCi）治疗剂量的（177）Lu-DOTA-TATE，放射化学纯度>99%，且保质期足够长。在正常Wistar大鼠中进行的生物学研究表明，除肾脏外，任何重要器官/组织均无明显的放射性积聚，未积聚的放射性主要通过肾脏清除。在癌症患者中进行的临床研究表明，癌灶和转移部位有放射性积聚。
该试剂盒有助于方便地制备适合人体给药的（177）Lu-DOTA-TATE治疗剂量。使用该试剂盒有望减少批次失败率和工作人员的辐射暴露。
