Radiopharmaceutical development of a freeze-dried kit formulation for the preparation of [99mTc-EDDA-HYNIC-D-Phe1, Tyr3]-octreotide, a somatostatin analog for tumor diagnosis



[99mTc-EDDA-HYNIC-D-Phe1,Tyr3]-Octreotide (99mTc-EDDA/HYNIC-TOC) is a promising new radiopharmaceutical with the potential to replace [111In-DTPA-D-Phe1]-Octreotide (111In-DTPA-OCT) as the radiopharmaceutical for somatostatin receptor scintigraphy due to the advantage of improved image quality, lower radiation dose for the patient, and daily availability. Here we describe the development of a freeze-dried kit formulation based on the Tricine/EDDA exchange labeling approach for the preparation of this radiopharmaceutical in a clinical setting. Three parameters were of major importance to achieve a suitable formulation with a radiochemical purity (RCP) >90%: addition of bulking agent, the pH of the freeze-drying solution, and the content of stannous chloride. The final formulation consisted of 20 mg Tricine, 10 mg EDDA, 50 mg Mannitol, 20 μg SnCl2 · 2H2O, and 20 μg [HYNIC-D-Phe1, Tyr3]-Octreotide (HYNIC-TOC). Radiolabeling was performed by addition of 0.2 M Na2HPO4 to adjust the pH to 6–7, followed by 0.5–2 GBq 99mTc sodium pertechnetate, in a total volume of 2 mL and incubation for 10 min in a boiling water bath. Mean RCP values of 10 batches showed values >90% over a storage period of up to 1 year, a high stability up to 24 h of the final preparation, and retained biological activity. The developed kit formulation forms the basis for further clinical evaluation of this promising new radiopharmaceutical. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2497–2506, 2004