Optimization of labeling PSMAHBED with 68Ga and its quality control systems

Radiolabeling of the prostate-specific membrane antigen (PSMA) inhibitor, Glu-NH-CO-NH-Lys (Ahx), using the (68)Ga chelator HBED-CC (PSMAHBED) allows imaging of lesions of prostate cancer due to the high expression of PSMA in prostate carcinoma cells as well as bone metastases and lymph nodes related to the disease.

The aim of this work was the optimization of the labeling of (68)Ga-PSMAHBED using the efficient cation exchange (CEX) post-processing of (68)Ga as well as the development of a TLC-based quality control system. Labeling was optimized for online ethanol post-processed (68)Ga eluate investigating various parameters, such as buffer molarity (0.1-1 M), temperature (25-90°C), tracer amount (0.11-0.74 nmol) and labeling time. In addition purification of the crude product using a STRATA-X cartridge was tested. For radio-TLC quality control various mobile phases were analyzed using silica gel 60 plates and results were validated using HPLC. The most superior mobile phases were also applied on ITLC-SG-plates. Using optimized conditions labeling yields of > 95% were obtained within 10 min when applying the ethanol-based post-processing using PSMAHBED amounts as low as 0.1 nmol. Higher precursor concentration (0.7 nmol) further increased labeling and quantitative yields to >98% within 5 min. In clinical routine patient batches (> 200 applications) with radiochemical purity > 98 % and specific activities of 326 ± 20 MBq/nmol are obtained reproducibly. Performing TLC quality control on silica gel 60 plates, four mobile phases with suitable separation properties and complementary Rf values were identified. Two systems show equivalent separation on ITLC-SG-plates, with ITLC analysis finished within 5 min in contrast to the TLC system (20 min). Labeling of PSMAHBED was optimized for CEX post-processing methods ensuring almost quantitative labeling and high nuclide purity of final (68)Ga-PSMAHBED, making subsequent purification steps unnecessary. The new radioTLC-method allows quality control in a short time using a fast, reliable, low cost method with little equipment effort. Using this approach, the synthesis is easily adopted by automated synthesis modules such as e.g. the EZAG Modular-Lab eazy.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017 Jan 12 [Epub ahead of print]

Elisabeth Eppard, Tatjana Homann, Ana de la Fuente, Markus Essler, Frank Roesch

University Hospital Bonn, Germany., University Mainz, Germany.

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