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 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 lymphaticand metastatic lesions. The 68 Ga-DKFZ-PSMA-11 kit is a robust, ready-to-use diagnostic agent in prostate cancer with high diagnostic performance.

Introduction: Human antimicrobial peptides are of interest for the development of positron

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Noninvasive imaging is a powerful tool for early diagnosis and monitoring of various disease processes, such as infections. An alarming shortage of infection-selective radiopharmaceuticals exists for overcoming the diagnostic limitations with unspecific tracers such as 67/68Ga-citrate or 18F-FDG. We report here TBIA101, an antimicrobial peptide derivative that was conjugated to DOTA and radiolabeled with 68Ga for a subsequent in vitro assessment and in vivo infection imaging using Escherichia coli-bearing mice by targeting bacterial lipopolysaccharides with PET/CT. Following DOTA-conjugation, the compound was verified for its cytotoxic and bacterial binding behaviour and compound stability, followed by 68Gallium-radiolabeling. µPET/CT using 68Ga-DOTA-TBIA101 was employed to detect muscular E. coli-infection in BALB/c mice, as warranted by the in vitro results. 68Ga-DOTA-TBIA101-PET detected E. coli-infected muscle tissue (SUV = 1.3–2.4) > noninfected thighs (P = 0.322) > forearm muscles (P = 0.092) > background (P = 0.021) in the same animal. Normalization of the infected thigh muscle to reference tissue showed a ratio of 3.0 ± 0.8 and a ratio of 2.3 ± 0.6 compared to the identical healthy tissue. The majority of the activity was cleared by renal excretion. The latter findings warrant further preclinical imaging studies of greater depth, as the DOTA-conjugation did not compromise the TBIA101's capacity as targeting vector.

The labeling of peptides with gallium-68 is often initially performed by manual labeling, but with high clinical demand, other alternatives are needed. Coldkits or automated synthesis are viable options for standardized methods and deemed pharmaceutically more acceptable. This study compares these [ 68 Ga] Ga-PSMA-11 production methods. Data from 40 kit-based and 40 automated syntheses of [ 68 Ga]Ga-PSMA-11 were analyzed. Pre-set criteria were evaluated including radiochemical purity, radionuclidic purity, chemical purity, physiological acceptability and sterility. The operator time and radiation dose received were measured. The robustness and repeatability of each method were assessed and a comparison of the running costs of each method is also provided. For both the methods all the analyzed products met the release criteria. No differences were found in radiochemical purity, radiochemical identity, radionuclidic purity, and sterility. However, radiochemical yield and apparent molar activity showed significant differences. For both methods, whole body radiation exposure to operators was lower than with manual labeling (25-40 μSv). The exposure during kit-based labeling (14.5 ± μSv) was seven times higher than that of automated synthesis (2.05 ± 0.99 μSv). The automated synthesis was the more expensive method. Both methods are sound alternatives to manual synthesis and offer higher quality, better radiation protection and a more reliable manufacturing of radiopharmaceuticals.