The History of Prostate-Specific Membrane Antigen as a Theranostic Target in Prostate Cancer: The Cornerstone Role of the Prostate Cancer Foundation

Abstract

Prostate-specific membrane antigen (PSMA) is a credentialed imaging and therapy (theranostic) target for the detection and treatment of prostate cancer. PSMA-targeted PET imaging and molecular radiotherapy are promising evolving technologies that will improve the outcomes of prostate cancer patients. In anticipation of this new era in prostate cancer theranostics, this article will review the history of PSMA from discovery through early-and late-stage clinical trials. Since 1993, the Prostate Cancer Foundation has funded critical and foundational PSMA research that established this theranostic revolution. The history and role of Prostate Cancer Foundation funding in this field will be discussed.

Dual targeting with 224Ra/212Pb-conjugates for targeted alpha therapy of disseminated cancers: A conceptual approach

“…In addition, the combination of 177 Lu-PSMA-I&T and 225 Ac-J591 for progressive mCRPC (33 patients) is being evaluated in an ongoing phase I/II clinical study in the United States ( ClinicalTrials.gov Identifier: NCT04886986). It has been hypothesized that additive radiation to PSMA-positive cells should occur when administering the radiopharmaceuticals concurrently since the monoclonal antibody (mAb) J591 and the small molecule ligand PSMA-I&T have different PSMA binding sites ( 21 ). Additionally, the team hypothesized that 225 Ac-J591 could deliver antitumor activity without xerostomia ( 21 , 22 ), that is the most common side effect of PSMA-TAT with small molecule ligands ( 13 ).…”

The 28th Annual Prostate Cancer Foundation Scientific Retreat report

“…PSMA theranostics have made significant headway recently, with PET imaging agents 68 Ga‐PSMA‐11 and 18 F‐DCFPyL, and the beta‐emitting molecular radiotherapy (MRT) 177 Lu‐PSMA‐617 (LuPSMA), receiving FDA approval. A history of PSMA theranostics has recently been published 58 …”

“…A history of PSMA theranostics has recently been published. 58 Michael Hofman (Peter MacCallum Cancer Centre; Prostate Cancer Theranostics and Imaging Centre of Excellence (ProSTIC)) reviewed some of the key clinical studies in the development of PSMA PET and LuPSMA.…”

Positron emission tomography: Evolving modalities, radiopharmaceuticals and professional collaboration

“…PSMA is physiologically expressed in the prostate and several other organs in the body, however, its high rate of expression of primary prostate cancer and nodal disease (approximately 95%) drove its development as a specific tracer for assessment and treatment of prostate cancer. 5 Two radiopharmaceuticals emerged for PSMA PET imaging ( 68 Ga-PSMA-11 and 18 F-DCFPyL) which served important clinical utility for staging, treatment monitoring and radiotherapy planning, with PSMA PET/CT shown to have high diagnostic utility compared with some conventional imaging methods such as bone scan and diagnostic CT. 6 Neuroendocrine tumours are represented in a small but unique subset of oncology patients. Targeted imaging in this group is not new, with the single-photon emitting 111 In-Octreotide exploiting the propensity of these tumours to express somatostatin receptors.…”

“…Building on discoveries in the late 1980s and 1990s, radiopharmaceuticals targeting prostate‐specific membrane antigen (PSMA) were developed through the early 2000s. PSMA is physiologically expressed in the prostate and several other organs in the body, however, its high rate of expression of primary prostate cancer and nodal disease (approximately 95%) drove its development as a specific tracer for assessment and treatment of prostate cancer 5 . Two radiopharmaceuticals emerged for PSMA PET imaging ( 68 Ga‐PSMA‐11 and 18 F‐DCFPyL) which served important clinical utility for staging, treatment monitoring and radiotherapy planning, with PSMA PET/CT shown to have high diagnostic utility compared with some conventional imaging methods such as bone scan and diagnostic CT 6 …”