PSMA-Targeted Radiopharmaceuticals for Imaging and Therapy.

  title={PSMA-Targeted Radiopharmaceuticals for Imaging and Therapy.},
  author={Hans-J{\"u}rgen Wester and Margret Schottelius},
  journal={Seminars in nuclear medicine},
  volume={49 4},
As described in more detail in other contributions in this issue of Seminars in Nuclear Medicine, prostate-specific membrane antigen (PSMA) has become one of the most promising molecular targets in nuclear medicine. Due to its overexpression on prostate cancer cells in proportion to the stage and grade of tumour progression, especially in androgen-independent, advanced and metastatic disease, various tracers for the detection and treatment of prostate cancer by means of radioligand imaging… 

The Future of PSMA-Targeted Radionuclide Therapy: An Overview of Recent Preclinical Research

This review will give an overview of the recent preclinical research projects regarding PCa-TRT using PSMA-specific radiotracers to give an indication of where the PSMA -TRT research movement is going and what the authors can expect in future clinical trials.

PSMA Radioligand Uptake as a Biomarker of Neoangiogenesis in Solid Tumours: Diagnostic or Theragnostic Factor?

The current status of the literature on PSMA radioligands’ application in solid tumours other than prostate cancer is described to explore their potential role as diagnostic or therapeutic agents, with particular regard to the relevance of PSMA Radioligand uptake as neoangiogenetic biomarker.

Extensive preclinical evaluation of lutetium-177-labeled PSMA-specific tracers for prostate cancer radionuclide therapy

Based on the preclinical evaluation, [177Lu]Lu-PSMA-617 is the best performing tracer to be taken further into clinical evaluation for PSMA-targeted radiotherapeutic development although with careful evaluation of the tracer binding to PSma-expressing organs.

A Review on the Current State and Future Perspectives of [99mTc]Tc-Housed PSMA-i in Prostate Cancer

This review aims to give an overview of the specific features of the developed [99mTc]Tc-tagged PSMA agents with particular attention to [99tc-PSMA-i], highlighting the pros and cons with respect to [68Ga]Ga-PSma11.

A simple strategy to reduce the salivary gland and kidney uptake of PSMA targeting small molecule radiopharmaceuticals

U uptake of PSMA TRT agents in salivary gland and kidney can be substantially reduced without impact on tumor uptake by adding cold PSMA-11, and it is proposed that similar strategy be pursued in future clinical trials to prevent xerostomia and renal toxicity arising from [177Lu]-PSMA-617.

Guiding management of therapy in prostate cancer: time to switch from conventional imaging to PSMA PET?

Despite high sensitivity and specificity, PSMA PET/CT as a single modality for staging advanced prostate cancer is suboptimal, given the low PSMA expression in this subgroup and the complementary role of fluorodeoxyglucose (FDG)PET/CT is required.

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177).

The switch from chelator HBED-CC to DOTA(GA)2 and the switch from the imaging isotope gallium-68 to the therapeutic isotope lutetium-177 have successfully transformed a PSMA-targeting agent from diagnosis to promising radionuclide therapeutic agents.

Antibodies targeting Prostate-Specific Membrane Antigen positive prostate cancer: from diagnostic imaging to theranostics

Although some clinical trials resulted in unfavorably safety profiles for some antibodies, they validated PSMA as a crucial immunoconjugate target, for both imaging and therapeutic settings.

Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer

An automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11 was standardized and the product was evaluated, thus verifying its characteristics for PET imaging of PCa tumors in a clinical environment.



Metal-Based PSMA Radioligands

This review focuses on the development and further applications of metal-based PSMA radioligands, which have been labeled with various diagnostic and/or therapeutic radiometals for single-photon-emission tomography, positron-emmission-tomography (PET), radionuclide targeted therapy as well as intraoperative applications.

Radiolabeled prostate-specific membrane antigen small-molecule inhibitors.

  • Leon WillI. SonniK. KopkaC. KratochwilF. GieselU. Haberkorn
  • Biology, Medicine
    The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of...
  • 2017
The currently available data clearly shows that PSMA targeting has a clinical impact on the diagnosis of PC, and that RLT using radiolabeled PSMA tracers has high potentiality in the settings of resistance to conventional therapeutic approaches.

Trifunctional PSMA-targeting constructs for prostate cancer with unprecedented localization to LNCaP tumors

The high tumor uptake achieved with these trifunctional ligands predicts larger doses delivered to the tumor than can be achieved with 177Lu-PSMA-617, and the exceptional area under the curve (AUC) in the tumor warrants further investigation of these novel ligands as candidates for RLT.

64Cu-Labeled Inhibitors of Prostate-Specific Membrane Antigen for PET Imaging of Prostate Cancer

Five 64Cu-labeled inhibitors of PSMA, [64Cu]3–7, which are based on the lysine–glutamate urea scaffold and utilize a variety of macrocyclic chelators, are reported, to determine which provides the most suitable pharmacokinetics for in vivo PET imaging.

PMPA for Nephroprotection in PSMA-Targeted Radionuclide Therapy of Prostate Cancer

PSMA-targeted radionuclide therapy can benefit from serial PMPA comedication by reducing off-target radiation to the kidneys, although in patients an optimization of the dose and time schedule may be necessary.

[68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECH

The initial experience with Ga-PSMA PET/CT strongly suggests that this novel method can detect prostate carcinoma relapses and metastases with significantly improved contrast compared to F-FECHPET/CT.

213Bi-PSMA-617 targeted alpha-radionuclide therapy in metastatic castration-resistant prostate cancer

The first-in-human treatment concept with Bi-PSMA-617 is presented in a patient with mCRPC that was progressive under conventional therapy and showed a remarkable molecular imaging response.

Prostate-specific membrane antigen as a target for cancer imaging and therapy.

  • A. KiessS. Banerjee M. Pomper
  • Biology, Medicine
    The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of...
  • 2015
Targeting PSMA may provide a viable alternative or first-line approach to managing prostate and other cancers, and may overtake FDG for certain indications.

Preclinical Development of Novel PSMA-Targeting Radioligands: Modulation of Albumin-Binding Properties To Improve Prostate Cancer Therapy.

177Lu-PSMA-ALB-56 was more effective to treat tumors than 177Lu- PSMA-617 resulting in complete tumor remission in four out of six mice, indicating that the p-(tolyl)-moiety was more suited as an albumin binder to optimize the tissue distribution profile.