Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy

Abstract

The prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PC) cells. Therefore, the targeting of PSMA has become increasingly important over the last decade. Glu-ureabased PSMA ligands used for both imaging and radioligand therapy are the mainstays of the current success. For PET imaging, both 68 Gaand 18 F-labeled agents have been successfully translated to clinical applications. Mainly retrospective cohort studies have shown a high value in the setting of biochemical recurrence, with high detection rates even in the presence of low prostate-specific antigen levels. Preliminary data indicated that radioguided surgery with PSMA ligands may help to further improve patient outcomes because it facilitates the removal of small tumor deposits that are otherwise difficult to detect. For primary PC, PSMA ligand PET imaging has been shown to be superior to cross-sectional imaging for the detection of metastatic lymph nodes. In addition, it promises to also provide intraprostatic tumor localization, especially when used in combination with multiparametric MRI. Increasing numbers of studies have reported considerable changes in management resulting from PSMA ligand PET imaging for both biochemical recurrence and primary disease. The use of 177 Lu-PSMA-based radioligand therapy has demonstrated a reasonable response, mainly as defined by a prostate-specific antigen response of more than 50%, comparable to other recently introduced agents. Especially given the high level of safety of 177 Lu-PSMA radioligand therapy, with only minimal grade 3 and 4 toxicities reported so far, it has the potential to expand options for metastatic castrationresistant PC. This review is intended to provide a comprehensive overview of the current literature on low-molecular-weight PSMA ligands for both PET imaging and therapeutic approaches, with a focus on agents that have been clinically adopted.

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

“…Newer and more sensitive imaging studies (e.g., prostate-specific membrane antigen positron-emission tomography) have identified metastases in some patients with no evidence of metastases on conventional imaging. [11][12][13] The regulatory approvals of currently marketed treatments for metastatic castration-resistant prostate cancer were based on the results of clinical trials involving men with metastases that were detected on conventional imaging, such as a bone scan or CT. It is possible that more sensitive imaging tests could have identified metastases at baseline in many of the patients in our trial, particularly because of the requirement for a short PSA doubling time at trial entry.…”

PSMA Ligands for PET Imaging of Prostate Cancer

“…18 F-labeled agents include 18 F-DCFBC (30,31), 18 F-DCFPyL (32), and 18 F-PSMA 1007 (33). They exploit the average lower positron range (reducing blurring effects), longer half-life, and potential for centralized production and distribution of 18 F compared with 68 Ga. A tabular overview of the most common PSMA ligands in clinical use was recently published (34).…”

Bispecific radioligands targeting prostate‐specific membrane antigen and gastrin‐releasing peptide receptors on the surface of prostate cancer cells

“…2 Nevertheless, in many patients, despite achieving medical castration, an increase in the PSA level takes place, indicating disease progression and the onset of metastatic castrationresistant PCa (mCRPC), which is considered to be the lethal form of the disease. 3 Reactivation of androgen receptor signaling occurs in early mCRPC; therefore, second-line agents targeting the androgen receptor (ie, Abiraterone and Enzalutamide) have extended survival in clinical trials. 4,5 Treatment with other systemic agents, including taxane-based chemotherapy (e.g., docetaxel), sipuleucel-T, and the bone-seeking alpha-emitter 223 Ra (Xofigo, formerly Alpharadin), has been shown to improve overall survival and quality of life.…”