title: Optimization of Labeling PSMAHBEDwith Ethanol-Postprocessed68Ga and Its Quality Control Systems.
abstract: Radiolabeling of the prostate-specific membrane antigen (PSMA) inhibitor Glu-NH-CO-NH-Lys(Ahx) using the68Ga chelator HBED-CC (PSMAHBED) allows imaging of prostate cancer lesions because of high expression of PSMA in prostate carcinoma cells and in bone metastases and lymph nodes related to the disease. The aim of this work was to optimize labeling of68Ga-PSMAHBEDusing the efficient cation-exchange postprocessing of68Ga as well as the development of a thin-layer chromatography (TLC)-based quality control system.Methods:Labeling was optimized for online ethanol-postprocessed68Ga eluate investigating various parameters, such as buffer molarity (0.1-1 M), temperature (25°C-90°C), tracer amount (0.11-0.74 nmol), and labeling time. In addition, purification of the crude product was tested. For radio-TLC quality control, various mobile phases were analyzed using silica gel 60 plates and the results were validated using high-performance liquid chromatography. The most superior mobile phases were also applied on instant thin-layer chromatography (ITLC) silica gel plates.Results:Using optimized conditions, labeling yields of more than 95% were obtained within 10 min when ethanol-based postprocessing was applied using PSMAHBEDamounts as low as 0.1 nmol. A higher precursor concentration (0.7 nmol) further increased labeling and quantitative yields to more than 98% within 5 min. In clinical routine, patient batches (>200 applications) with radiochemical purity greater than 98% and specific activities of 326 ± 20 MBq/nmol are obtained reproducibly. When TLC quality control was performed on silica gel 60 plates, 4 mobile phases with suitable separation properties and complementary Rfvalues were identified. Two systems showed equivalent separation on ITLC silica gel plates, with ITLC analysis finished within 5 min, in contrast to 20 min for the TLC system. Labeling of PSMAHBEDwas optimized for cation-exchange postprocessing methods, ensuring almost quantitative labeling and high nuclide purity of final68Ga-PSMAHBED, making subsequent purification steps unnecessary.Conclusion:The new radio-TLC method allows quality control in a short time using a fast, reliable, low-cost method with little equipment complexity. Using this approach, the synthesis is easily adopted by automated synthesis modules.
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany; and.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Eppard
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Homann
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: de la Fuente
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany; and.
authors.forename: Markus
authors.initials: M
authors.lastname: Essler
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg University, Mainz, Germany frank.roesch@uni-mainz.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Rösch
mesh_terms: D000954:Antigens, Surface / Q000737:chemistry*; D004340:Drug Contamination / Q000517:prevention & control*; D004492:Edetic Acid / Q000031:analogs & derivatives; D005709:Gallium Isotopes; D005710:Gallium Radioisotopes / Q000032:analysis / Q000737:chemistry* / Q000592:standards; D005858:Germany; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry* / Q000592:standards; D007553:Isotope Labeling / Q000379:methods* / Q000592:standards; D009842:Oligopeptides; D009942:Organometallic Compounds / Q000032:analysis / Q000138:chemical synthesis* / Q000592:standards; D011786:Quality Control; D011876:Radionuclide Generators / Q000592:standards; D019275:Radiopharmaceuticals / Q000032:analysis / Q000138:chemical synthesis* / Q000592:standards
chemical_list: D000954:Antigens, Surface; D005709:Gallium Isotopes; D005710:Gallium Radioisotopes; D009842:Oligopeptides; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C000718244:gallium 68 PSMA-11; D004492:Edetic Acid; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: 68Ga; ITLC; PSMA; generator postprocessing; quality control