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.
[(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.
Guggenberg
Elisabeth Von
EV
Clincal Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria. elusabeth.vonguggenberg@uklibk.ac.at
Mikolajczak
Renata
R
Janota
Barbara
B
Riccabona
Georg
G
Decristoforo
Clemens
C
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
D015609:Organotechnetium Compounds; D019999:Pharmaceutical Solutions; D019275:Radiopharmaceuticals; D011933:Reagent Kits, Diagnostic; D013004:Somatostatin; D015282:Octreotide