Development of a Single Vial Kit Solution for Radiolabeling of 68Ga-DKFZ-PSMA-11 and Its Performance in Prostate Cancer Patients.
Prostate-specific membrane antigen (PSMA), a type II glycoprotein, is highly expressed in almost all prostate cancers. By playing such a universal role in the disease, PSMA provides a target for diagnostic imaging of prostate cancer using positron emission tomography/computed tomography (PET/CT). The PSMA-targeting ligand Glu-NH-CO-NH-Lys-(Ahx)-HBED-CC (DKFZ-PSMA-11) has superior imaging properties and allows for highly-specific complexation of the generator-based radioisotope Gallium-68 ((68)Ga). However, only module-based radiolabeling procedures are currently available. This study intended to develop a single vial kit solution to radiolabel buffered DKFZ-PSMA-11 with (68)Ga. A (68)Ge/(68)Ga-generator was utilized to yield (68)GaCl3 and major aspects of the kit development were assessed, such as radiolabeling performance, quality assurance, and stability. The final product was injected into patients with prostate cancer for PET/CT imaging and the kit performance was evaluated on the basis of the expected biodistribution, lesion detection, and dose optimization. Kits containing 5 nmol DKFZ-PSMA-11 showed rapid, quantitative (68)Ga-complexation and all quality measurements met the release criteria for human application. The increased precursor content did not compromise the ability of (68)Ga-DKFZ-PSMA-11 PET/CT to detect primary prostate cancer and its advanced lymphatic- and metastatic lesions. The (68)Ga-DKFZ-PSMA-11 kit is a robust, ready-to-use diagnostic agent in prostate cancer with high diagnostic performance.
University of Pretoria & Steve Biko Academic Hospital, Crn Malherbe and Steve Biko Rd, Pretoria 0001, South Africa. Thomas.ebenhan@gmail.com.|School of Health Sciences, Catalysis and Peptide Research Unit, E-Block 6th Floor, Westville Campus, University Road, Westville, Durban 3630, South Africa. Thomas.ebenhan@gmail.com.
Thomas
T
Ebenhan
University of Pretoria & Steve Biko Academic Hospital, Crn Malherbe and Steve Biko Rd, Pretoria 0001, South Africa. marizavorster@gmail.com.
Mariza
M
Vorster
The South African Nuclear Energy Corporation (Necsa), Building P1600, Radiochemistry, Pelindaba, Brits 0240, South Africa.
Biljana
B
Marjanovic-Painter
The South African Nuclear Energy Corporation (Necsa), Building P1600, Radiochemistry, Pelindaba, Brits 0240, South Africa. judith.wagener@necsa.co.za.
Judith
J
Wagener
University of Pretoria & Steve Biko Academic Hospital, Crn Malherbe and Steve Biko Rd, Pretoria 0001, South Africa. janine.suthiram@necsa.co.za.|The South African Nuclear Energy Corporation (Necsa), Building P1600, Radiochemistry, Pelindaba, Brits 0240, South Africa. janine.suthiram@necsa.co.za.
Janine
J
Suthiram
University of Pretoria & Steve Biko Academic Hospital, Crn Malherbe and Steve Biko Rd, Pretoria 0001, South Africa. modisellemoshe@yahoo.co.uk.
Moshe
M
Modiselle
University of Pretoria & Steve Biko Academic Hospital, Crn Malherbe and Steve Biko Rd, Pretoria 0001, South Africa. tshelom@gmail.com.
Brenda
B
Mokaleng
Department of Science and Technology, Preclinical Drug Development Platform, North West University, 11 Hoffman St, Potchefstroom 2520, South Africa. janrijn.zeevaart@necsa.co.za.
Jan Rijn
JR
Zeevaart
University of Pretoria & Steve Biko Academic Hospital, Crn Malherbe and Steve Biko Rd, Pretoria 0001, South Africa. Mike.Sathekge@up.ac.za.
Mike
M
Sathekge
D002851:Chromatography, High Pressure Liquid; D004492:Edetic Acid / Q000031:analogs & derivatives; D005709:Gallium Isotopes; D005710:Gallium Radioisotopes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009842:Oligopeptides; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D011933:Reagent Kits, Diagnostic; D015203:Reproducibility of Results; D012996:Solutions; D014057:Tomography, X-Ray Computed; D051598:Whole Body Imaging
D005709:Gallium Isotopes; D005710:Gallium Radioisotopes; D009842:Oligopeptides; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D011933:Reagent Kits, Diagnostic; D012996:Solutions; C000718244:gallium 68 PSMA-11; D004492:Edetic Acid
68Ga-DKFZ-PSMA-11; 68Ga-HBED-CC-(Ahx)Lys-NH-CO-NH-Glu; 68Ga-PSMAHBED; PET/CT; PSMA; prostate cancer