Development of a Single Vial Kit Solution for Radiolabeling of 68Ga-DKFZ-PSMA-11 and Its Performance in Prostate Cancer Patients

Abstract

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.

Preclinical assessment of 68Ga‐PSMA‐617 entrapped in a microemulsion delivery system for applications in prostate cancer PET/CT imaging

“…Quality control of [ 68 Ga]Ga‐PSMA‐617 followed previously published described methods for high performance liquid chromatography (HPLC) and instant‐thin layer chromatography (ITLC) . A reverse‐phase HPLC column (Zorbax StableBond C18, 0.46 × 2 cm × 5 μm; Agilent Technologies, CA, USA) performing gradient elution (5%‐95% A‐B over 15 minutes) at a flow rate of 1 mL/min was employed (Solvent A = 0.1% aqueous trifluoroacetic acid [TFA]; solvent B = 0.1% TFA in acetonitrile).…”

68Ga or18F for Prostate Cancer Imaging?

“…For centers that do not have access to a cyclotron and have a moderate number of examinations, these generators present a reasonably priced upfront investment. PSMA-11 contains the chelator HBED-CC (N,N9-bis [2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-N,N9-diacetic acid), which allows labeling with kit formulations at ambient temperature without critical radiochemistry demands (10,11). However, 68 Ga has a physical half-life of only 68 min.…”

Diagnostic sensitivity of Tc-99m HYNIC PSMA SPECT/CT in prostate carcinoma: A comparative analysis with Ga-68 PSMA PET/CT

“…Ga‐68 was obtained from a Ge‐68/Ga‐68 generator (iThemba LABS, Somerset West, South Africa). Synthesis of Ga‐68 DKFZ‐PSMA‐11 was done in‐house as we have previously reported . Radiochemical purity was above 98% in all syntheses administered to patients for imaging.…”