[68Ga]Ga-PSMA-11: The First FDA-Approved 68Ga-Radiopharmaceutical for PET Imaging of Prostate Cancer

Ute Hennrich, Matthias Eder, Ute Hennrich, Matthias Eder

Abstract

For the positron emission tomography (PET) imaging of prostate cancer, radiotracers targeting the prostate-specific membrane antigen (PSMA) are nowadays used in clinical practice. Almost 10 years after its discovery, [68Ga]Ga-PSMA-11 has been approved in the United States by the Food and Drug Administration (FDA) as the first 68Ga-radiopharmaceutical for the PET imaging of PSMA-positive prostate cancer in 2020. This radiopharmaceutical combines the peptidomimetic Glu-NH-CO-NH-Lys(Ahx)-HBED-CC with the radionuclide 68Ga, enabling specific imaging of tumor cells expressing PSMA. Such a targeting approach may also be used for therapy planning as well as potentially for the evaluation of treatment response.

Keywords: PSMA; [68Ga]Ga-PSMA-11; positron emission tomography (PET); prostate cancer; theranostics.

Conflict of interest statement

M.E. holds patent rights on PSMA inhibitors.

Figures

Figure 1
Figure 1
The pharmacokinetic and binding properties of 68Ga-labeled PSMA targeting urea-based inhibitors are clearly affected by the exact composition of the linker and the presence of aromatic moieties. In case the linker is entirely aliphatic (PSMA-Ahx-DOTA), the affinity and internalization are low or lost, respectively, and the tracer is mainly localized in the liver without any detectable signal in the tumor. By introducing aromatic moieties in the linker region as represented by PSMA-(AMBA)2-DOTA, the compound exhibits better affinity and starts to show significant internalization of the tracer in the tumor cell, resulting in a visible tumor uptake and a changed PK profile. One of the unique characteristics of PSMA-11 is that the chelator HBED-CC takes over these functional requirements by its aromatic moieties and, therefore, interacts well with the binding pocket, resulting in a promising in vivo performance of the entire molecule. Data were obtained from previously published studies using LNCaP cells for the determination of affinity and internalization and LNCaP-tumor-bearing BALB/c nu/nu mice for PET imaging [13,14].
Figure 2
Figure 2
Chemical structure of [68Ga]Ga-PSMA-11.

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