PSMA PET and Radionuclide Therapy in Prostate Cancer

Abstract

Prostate cancer (Pca) is the most common malignancy in men and a major cause of cancer death. Accurate imaging plays an important role in diagnosis, staging, restaging, detection of biochemical recurrence, and for therapy of PCa patients. Since no effective treatment is available for advanced PCa, there is an urgent need to develop new and more effective therapeutic strategies. In order to optimize treatment outcome, especially in high risk PCa patients, therapy of PCa is moving rapidly towards personalization. Medical imaging, including positron emission tomography (PET)/computed tomography (CT), plays an important role in personalized medicine in oncology. In the recent years, much focus has been on prostate specific membrane antigen (PSMA) as a promising target for imaging and therapy with radionuclides, since it is upregulated in most PCa. In the prostate, one potential role for PSMA PET imaging is to help guiding focal therapy. Several studies have shown great potential of PSMA PET/CT for initial staging, lymph node staging, and detection of recurrence of PCa, even at very low PSA values after primary therapy. Furthermore, studies have shown that PSMA PET/CT has a higher detection rate than choline PET/CT. Radiolabeled PSMA ligands for therapy show promise in several studies with metastatic PCa, and is an area of active investigation. The “Image and treat” strategy, with radiolabeled PSMA ligands, has the potential to improve the treatment outcome of PCa patients, and is paving the way for precision medicine in PCa. The aim of this review is to give an overview of recent advancement in PSMA PET and radionuclide therapy of PCa.

Modular Synthesis of DOTA‐Metal‐Based PSMA‐Targeted Imaging Agents for MRI and PET of Prostate Cancer

“…The clinical limitations of nontargeted molecular imaging agents for prostate cancer (PCa) has led to an exponential increase of investigational targeted imaging agents for magnetic resonance imaging (MRI), positron emission tomography (PET), and single‐photon emission computed tomography (SPECT) in both preclinical and clinical research over the past five years . In particular, the use of targeted PET agents was found to be remarkably effective in the detection, staging, and active surveillance of PCa …”

“…PSMA, also known as glutamate carboxypeptidase II (GCPII), NAALADase, and folate hydrolase FOLH1, is a well‐characterized trans ‐membrane glycoprotein . Its expression is elevated with increasing PCa stage and grade making it an excellent biomarker for staging, metastasis detection, and image‐guided interventions . PSMA is also expressed on the neovasculature of other types of carcinomas such as breast and thyroid, making it an important biomarker in the larger scope of cancer research as well …”

“…[1,2] In particular, the use of targeted PET agents was found to be remarkably effective in the detection, staging, and active surveillance of PCa. [3][4][5][6][7][8] Ta rgeteda gentsf or MRI, as well as dual modal agentsf or SPECT/Optical Imaging, have also been shown to be effective in pre-clinical imaging of active PCa. [9][10][11][12][13] Recently,astudy using simultaneousP ET/MRI has reported remarkablyh igh accuracy( 80-97.5%)i nt he detection of multiple stages of PCa, underscoring the need for reliable synthetic methods for targeted probesfor both PET andM RI of PCa.…”

Initial evaluation of PET/CT with 18F‐FSU‐880 targeting prostate‐specific membrane antigen in prostate cancer patients

“…Recently, prostate‐specific membrane antigen (PSMA) has received attention as a target of imaging and therapy for prostate cancer . Prostate‐specific membrane antigen is a cell‐surface enzyme also known as glutamate carboxypeptidase II or folate hydrolase .…”

“…4 Recently, prostate-specific membrane antigen (PSMA) has received attention as a target of imaging and therapy for prostate cancer. 5 Prostate-specific membrane antigen is a cell-surface enzyme also known as glutamate carboxypeptidase II or folate hydrolase. 6 It is overexpressed on most prostate cancer cells and its expression increases in higher grade cancers and in metastatic and recurrent cancers.…”