PSMA Ligands for Radionuclide Imaging and Therapy of Prostate Cancer: Clinical Status

Susanne Lütje, Sandra Heskamp, Alexander S Cornelissen, Thorsten D Poeppel, Sebastiaan A M W van den Broek, Sandra Rosenbaum-Krumme, Andreas Bockisch, Martin Gotthardt, Mark Rijpkema, Otto C Boerman, Susanne Lütje, Sandra Heskamp, Alexander S Cornelissen, Thorsten D Poeppel, Sebastiaan A M W van den Broek, Sandra Rosenbaum-Krumme, Andreas Bockisch, Martin Gotthardt, Mark Rijpkema, Otto C Boerman

Abstract

Prostate cancer (PCa) is the most common malignancy in men worldwide, leading to substantial morbidity and mortality. At present, imaging of PCa has become increasingly important for staging, restaging, and treatment selection. Until recently, choline-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for these purposes. However, its application is limited to patients with high PSA levels and Gleason scores. Prostate-specific membrane antigen (PSMA) is a promising new target for specific imaging of PCa, because it is upregulated in the majority of PCa. Moreover, PSMA can serve as a target for therapeutic applications. Currently, several small-molecule PSMA ligands with excellent in vivo tumor targeting characteristics are being investigated for their potential in theranostic applications in PCa. Here, a review of the recent developments in PSMA-based diagnostic imaging and therapy in patients with PCa with radiolabeled PSMA ligands is provided.

Keywords: PET; PSMA; prostate cancer; radionuclide imaging; theranostics.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Classification of small molecule PSMA inhibitors used in (pre-)clinical studies for PCa. 1: urea-based glutamate heterodimers, 2: phosphoramidates, 3: 2-(phosphinylmethyl) pentanedioic acids
Figure 2
Figure 2
Small-molecule PSMA ligands currently being investigated for PCa imaging in clinical settings. All possess the characteristic glu-urea-lys core.
Figure 3
Figure 3
68Ga-HBED-CC-PSMA PET/CT image of a patient with locally recurrent PCa (PSA 3.7 ng/ml) after radical prostatectomy (SUVmax 12.4) who received 140 MBq of the 68Ga-labeled tracer molecule and was scanned at 1 h p.i.; a) CT image, b) PET image, c) PET/CT fusion image, d) MIP.
Figure 4
Figure 4
68Ga-HBED-CC-PSMA PET/CT (a, b) and PET/MRI (c, d) images of a patient with PCa with recurrent disease in an inguinal lymph node (PSA 0.9 ng/ml) after radical prostatectomy, scanned at 1 h and 3 h p.i., using PET/CT and PET/MRI, respectively. a) CT image, b) PET/CT fusion image, c) MR image (T2-weighted with contrast medium and turbo spin echo), d) PET/MRI fusion image. A metastatic lymph node is visible in the PET/MRI fusion image (green arrow), while the same lesion could not be visualized with PET/CT.
Figure 5
Figure 5
68Ga-HBED-CC-PSMA PET images of a patient with PCa after radical prostatectomy with recurrent disease in an inguinal lymph node. While the scatter corrected PET image from the PET/CT system (a) and the not scatter corrected PET image from the PET/MRI system (b) show no artefact, the scatter corrected PET image from the PET/MRI system shows an extensively reduced signal around the urinary bladder (b), previously described as 'halo' artefact .

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