Keeping up with the prostate-specific membrane antigens (PSMAs): an introduction to a new class of positron emission tomography (PET) imaging agents

Abstract

Prostate-specific membrane antigen (PSMA) targeted positron emission tomography (PET) is an emerging prostate cancer imaging method, which has been reported to have a higher sensitivity and specificity than the currently approved PET imaging agents. Multiple PSMA ligands are being investigated around the world and applications range from primary tumor characterization, to local staging, biochemical recurrence, metastasis, and image-guided interventions. The most investigated PET tracers are labelled with 68-Gallium or 18-Fluoride and are discussed in this review. Additionally, 99mTc labeled PSMA agents for single photon emission computed tomography (SPECT) imaging are elucidated as an alternative method of PSMA image acquisition.

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 …”

“…[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.…”

“…[20,21] Currently,t he PCa TMIAs most widely investigated are 68 Galabeled DCL probesf or PET imaging, with the agent 68 Ga-PSMA-11 (also known as 68 Ga-DKFZ-PSMA-11) being most prevalent in clinical studies. [3][4][5][6][7]14] While 68 Ga-DKFZ-PSMA-11e mploys an acyclic metal-chelating group,H BED-CC, the alternative and well-known cyclic chelator,1 ,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), is at the core of many other reported TMIAs for both PET and MRI of PCa. [17,[22][23][24] DOTAi sa lso the chelating moiety in 177Lu-PSMA-617, ana nalogousr adiotherapeutic agent in currentc linical use for PCa therapy.…”

PSMA PET ligands in prostate cancer: a game‐changer?

“…3 Radiolabelled PSMA ligands (Ga-68 and F-18) -of all available prostate cancer PET agents, PSMA ligands represent the biggest advance. [3][4][5][6][7][8] These are receptor agents (rather than metabolic markers) that bind to a surface transmembrane glycoprotein.…”

“…PSMA over-expression is also related to tumour grade and observed to increase with castrate resistance. 5,6 More recently, small-molecule PSMA ligands have been developed to harness the potential of this biomarker. These accumulate at very high levels within the tumour cell, conferring a high sensitivity for detecting small-volume disease.…”