RESUMEN
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.
Asunto(s)
Compuestos Organometálicos/síntesis química , Neoplasias de la Próstata/diagnóstico por imagen , Radiofármacos/síntesis química , Juego de Reactivos para Diagnóstico , Cromatografía Líquida de Alta Presión , Ácido Edético/análogos & derivados , Isótopos de Galio , Radioisótopos de Galio , Humanos , Concentración de Iones de Hidrógeno , Masculino , Oligopéptidos , Tomografía de Emisión de Positrones , Reproducibilidad de los Resultados , Soluciones , Tomografía Computarizada por Rayos X , Imagen de Cuerpo EnteroAsunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Ácido Edético/análogos & derivados , Oligopéptidos , Adulto , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Isótopos de Galio , Radioisótopos de Galio , Humanos , Imagen Multimodal , Metástasis de la Neoplasia , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
Our aim was to develop a practical method to prepare 68Ga-citrate using a SnO2-based 68Ge/68Ga generator and evaluate its use in infection imaging. 68Ga-citrate synthesis was performed in a straight forward, quantitative, one-step-aseptic procedure; an amended labeling method was applied using ACD-A buffered citrate as a precursor. Study participants were imaged on a Siemens Biograph 40 PET/CT scanner 60 min post intravenous injection. Our results showed: 90%-95% 68Ga-yield was obtained and subsequently used at 324-527 MBq to perform three to four parallel 68Ga-citrate syntheses. 68Ga-citrate of 96%-99% was yielded after 10 min incubation. The radiochemical purity was >99% with a pH value of 4.0-4.5. All other quality control requirements were met. The 68Ga-citrate stability was >96%. The final product was sterile, pyrogen and solvent-free, with very low 68Ge-levels, with 191±33 MBq in 6.6±2.8 mL. High quality images were obtained at 60 min post injection of 185 MBq of 68Ga-citrate. In conclusion, a fast, direct and cheap method with a quantitative preparation of 68Ga-citrate was described. We reported on the adaptations needed when using a SnO2-based 68Ge/68Ga generator and ACD-A buffered citrate as a precursor. This method allowed for multiple patient productions from one generator elution, with 300 MBq/patient of 68Ga-citrate produced in less than 30 min and excellent labeling reproducibility for routine infection imaging.
