title: 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.
abstract: [(99m)Tc-EDDA-HYNIC-D-Phe(1),Tyr(3)]-Octreotide ((99m)Tc-EDDA/HYNIC-TOC) is a promising new radiopharmaceutical with the potential to replace [(111)In-DTPA-D-Phe(1)]-Octreotide ((111)In-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 microg SnCl(2). 2H(2)O, and 20 microg [HYNIC-D-Phe(1), Tyr(3)]-Octreotide (HYNIC-TOC). Radiolabeling was performed by addition of 0.2 M Na(2)HPO(4) to adjust the pH to 6-7, followed by 0.5-2 GBq (99m)Tc 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.
authors.affiliation: Clincal Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria. elusabeth.vonguggenberg@uklibk.ac.at
authors.forename: Elisabeth Von
authors.initials: EV
authors.lastname: Guggenberg
authors.forename: Renata
authors.initials: R
authors.lastname: Mikolajczak
authors.forename: Barbara
authors.initials: B
authors.lastname: Janota
authors.forename: Georg
authors.initials: G
authors.lastname: Riccabona
authors.forename: Clemens
authors.initials: C
authors.lastname: Decristoforo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004355:Drug Stability; D004356:Drug Storage; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D009369:Neoplasms / Q000000981:diagnostic imaging; D015282:Octreotide / Q000138:chemical synthesis*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis*; D019999:Pharmaceutical Solutions; D011786:Quality Control; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D051381:Rats; D011933:Reagent Kits, Diagnostic; D015203:Reproducibility of Results; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013997:Time Factors
chemical_list: D015609:Organotechnetium Compounds; D019999:Pharmaceutical Solutions; D019275:Radiopharmaceuticals; D011933:Reagent Kits, Diagnostic; D013004:Somatostatin; D015282:Octreotide