Title:Toward the Discovery and Development of PSMA Targeted Inhibitors for Nuclear Medicine Applications
VOLUME: 13 ISSUE: 1
Author(s):Sara Pastorino, Mattia Riondato, Licia Uccelli, Giampiero Giovacchini, Elisabetta Giovannini, Valerio Duce and Andrea Ciarmiello*
Affiliation:Nuclear Medicine Department, S. Andrea Hospital, Via Vittorio Veneto 197, 19124 La Spezia, Nuclear Medicine Department, S. Andrea Hospital, Via Vittorio Veneto 197, 19124 La Spezia, Morphology, Surgery and Experimental Medicine Department, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Nuclear Medicine Department, S. Andrea Hospital, Via Vittorio Veneto 197, 19124 La Spezia, Nuclear Medicine Department, S. Andrea Hospital, Via Vittorio Veneto 197, 19124 La Spezia, Nuclear Medicine Department, S. Andrea Hospital, Via Vittorio Veneto 197, 19124 La Spezia, Nuclear Medicine Department, S. Andrea Hospital, Via Vittorio Veneto 197, 19124 La Spezia
Keywords:Prostate cancer, PSMA, molecular docking, PET, SPECT, imaging, radionuclide therapy.
Abstract:
Background: The rising incidence rate of prostate cancer (PCa) has promoted the development
of new diagnostic and therapeutic radiopharmaceuticals during the last decades. Promising improvements
have been achieved in clinical practice using prostate specific membrane antigen (PSMA)
labeled agents, including specific antibodies and small molecular weight inhibitors. Focusing on molecular
docking studies, this review aims to highlight the progress in the design of PSMA targeted
agents for a potential use in nuclear medicine.
Results: Although the first development of radiopharmaceuticals able to specifically recognize PSMA
was exclusively oriented to macromolecule protein structure such as radiolabeled monoclonal antibodies
and derivatives, the isolation of the crystal structure of PSMA served as the trigger for the synthesis
and the further evaluation of a variety of low molecular weight inhibitors. Among the nuclear imaging
probes and radiotherapeutics that have been developed and tested till today, labeled Glutamate-ureido
inhibitors are the most prevalent PSMA-targeting agents for nuclear medicine applications.
Conclusion: PSMA represents for researchers the most attractive target for the detection and treatment
of patients affected by PCa using nuclear medicine modalities. [99mTc]MIP-1404 is considered the tracer
of choice for SPECT imaging and [68Ga]PSMA-11 is the leading diagnostic for PET imaging by general
consensus. [18F]DCFPyL and [18F]PSMA-1007 are clearly the emerging PET PSMA candidates for
their great potential for a widespread commercial distribution. After paving the way with new imaging
tools, academic and industrial R&Ds are now focusing on the development of PSMA inhibitors labeled
with alpha or beta minus emitters for a theragnostic application.