PSMA Imaging Agents Moving Ahead in Prostate Cancer

Prostate-specific membrane antigen–targeting diagnostic agents are moving forward toward greater clinical use in PET imaging for prostate cancer.

Prostate-specific membrane antigen (PSMA)–targeting diagnostic agents are moving forward toward greater clinical use in positron emission tomography (PET) imaging for prostate cancer.

In December 2020, Gallium 68 PSMA-11 (68Ga-PSMA-11) was approved by the FDA as the first-ever drug for PET imaging of PSMA-positive lesions in men with prostate cancer.1 Prior to its approval, a New Drug Application (NDA) for TLX591-CDx (illumet), a companion diagnostic kit for the preparation of 68Ga-PSMA-11, was accepted for review by the FDA.2 And recently, the FDA accepted an NDA for PyL (18F-DCFPyL), a PSMA-targeted PET imaging agent, and granted the application a priority review.3

PSMA-targeting PET has been suggested to be a superior method for imaging in prostate cancer. Altogether, these 2 agents and the related radiopharmaceutical cold kit show that this imaging method is now being recognized as a significant tool for the assessment of prostate cancer.

“PSMA imaging is already included in the leading clinical practice guidelines in the United States and Europe, based on evidence that definitively demonstrates superiority over conventional imaging,” Colin Hayward, MD, chief medical officer of Telix Pharmaceuticals, in a press release.

“We believe that there is a significant unmet need for reliable, targeted imaging in prostate cancer, particularly in the high risk and biochemically recurrent populations,” said Istvan Molnar, MD, chief medical officer of Lantheus, in a statement upon announcement of the priority review designation. These 3 are looking to fill that unmet need.

PSMA is an antigen that is expressed on the cell surface and is overexpressed in many prostate cancer cells, especially in castrate-resistance disease, making it an attractive target for the identification of prostate cancer without significant concern of toxicity.

68Ga-PSMA PET/CT imaging is a diagnostic technique for the imaging of prostate cancer to identify increased PSMA expression that utilizes a PSMA-11 synthetic peptide. The TLX591-CDx kit prepares doses of 68Ga-PSMA-11 for use in PET imaging to detect recurrence in men with prostate cancer.2

Data from the NDA for TLX591-CDx came from clinical data from over 600 patients included in clinical trials.

PyL is a fluorinated PSMA-targeted PET imaging agent for visualization of localized disease and disease recurrence in prostate cancer. Data from the phase 2/3 OSPREY trial and the phase 3 CONDOR trial supported the NDA.3

The OSPREY trial explored the diagnostic use of PyL to detect prostate cancer in pelvic lymph nodes in patients with high-risk, locally advanced disease as well as for the detection of distant metastases in patients with metastatic or recurrent prostate cancer. Among patients with locally advanced disease, PyL showed a specificity rate of 96% to 99%, a sensitivity rate of 21% to 42%, and a positive predictive value of 78% to 91%. However, one of the primary end points of the trial were not met. Among patients with metastatic or recurrent disease, the sensitivity rate was 93% to 99% and the positive predictive value was 81% to 88%.

The CONDOR study evaluated the diagnostic use of PyL in men with biochemical recurrence of their disease. In results presented at the 2020 ASCO Virtual Scientific Program, PyL demonstrated a correct localization rate of 84.8% to 87.0% between 3 blinded independent readers and 63.9% of patients in the study had a change in their disease management plan due to the results of the imaging studies.

Based on these FDA actions, PSMA is clearly on the rise in the detection of prostate cancer, and PSMA-targeting therapies are not far behind in development, giving further clout to the use of PSMA as a target.


FDA Approves First PSMA-Targeted PET Imaging Drug for Men with Prostate Cancer. News release. FDA. December 1, 2020. Accessed December 23, 2020.

Lantheus Holdings Announces Acceptance and Priority Review of New Drug Application for PyLTM (18F-DCFPyL), a PSMA-Targeted Prostate Cancer PET Imaging Agent. News release. Lantheus Holdings. December 9, 2020. Accessed December 23, 2020.

Telix New Drug Application for Prostate Cancer Imaging Product Accepted by US FDA. News release. Telix Pharmaceuticals. November 24, 2020. Accessed December 23, 2020.