Formulation, Preclinical Evaluation, and Preliminary Clinical Investigation of an In-House Freeze-Dried EDTMP Kit Suitable for the Preparation of 177Lu-EDTMP.

Objective: The objective of the present work was to develop a freeze-dried ethylenediaminetetramethylene phosphonic acid (EDTMP) kit, suitable for the convenient and single-step preparation of 177Lu-EDTMP, which is currently being evaluated as a promising radiopharmaceutical for providing palliative care to patients suffering from skeletal metastases and to assess the potential of the agent in human patients. Experimental: Lyophilized EDTMP kits having identical composition with Quadramet® were prepared using EDTMP, NaOH, and anhydrous CaCO3. The 177Lu-EDTMP patient dose was prepared by incubating the kit materials dissolved in 1 mL of water for injection and 177LuCl3, produced in-house, at room temperature for 15 minutes. Pharmacokinetic behavior of the agent was studied by carrying out biodistribution and scintigraphic imaging studies in normal Wistar rats. Clinical studies were performed by administering the preparation in patients suffering from disseminated skeletal metastases. Results: Five batches of freeze-dried EDTMP kits with 50 kit vials in each batch were prepared. Each kit vial comprised a lyophilized mixture of 35 mg EDTMP, 14.1 mg NaOH, and 5.8 mg of CaCO3. The 177Lu-EDTMP complex was prepared with excellent radiochemical purity (>99%) and high stability (>98% until 9 days postpreparation) using these kits. Radiochemical studies showed that this kit could be used within a pH range of 6-9 and with 177Lu having specific activity as low as 925 GBq·g−1 (25 Ci·g−1) for the preparation of up to 3.7 GBq (100 mCi) of 177Lu-EDTMP. Biodistribution studies in animals revealed selective accumulation of the agent in skeleton (∼60% of the injected activity) with major renal clearance. Preliminary clinical studies in 10 patients exhibited selective accumulation of the radiotracer in skeletal lesions and provided significant pain relief thereby improving the quality of life of the patients. Conclusion: Freeze-dried EDTMP kits, suitable for the preparation of patient doses of 177Lu-EDTMP, have been developed and used in preliminary studies for treating the cancer patients with disseminated skeletal metastases. The kit may also find use for the preparation of other potential bone pain palliation agents, such as 153Sm-EDTMP. [ABSTRACT FROM AUTHOR]