Prostate-specific membrane antigen-directed imaging and radioguided surgery with single-photon emission computed tomography: state of the art and future outlook

ABSTRACT

Introduction

Prostate-specific membrane antigen (PSMA) has emerged as a highly relevant target for prostate cancer (PC) diagnosis and therapy. PSMA inhibitors targeting PSMA-enzymatic domain have been successfully labeled with radionuclides emitting positrons or gamma-photons, thus obtaining tracers suitable for imaging with positron emission computed tomography (PET/CT) or single-photon emission tomography (SPECT).

Areas covered

The different approaches for obtaining PSMA-ligands labeled with gamma-emitting nuclides (^99mTc or¹¹¹In) are reviewed. Furthermore, the applications of ^99mTc/¹¹¹In-PSMA SPECT for the imaging of PC patients in different clinical settings (staging or biochemical recurrence) are covered. Lastly, the employment of PSMA-targeted SPECT tracers for radioguided surgery (RGS) during primary or salvage lymphadenectomy is discussed.

Expert opinion

RGS provided satisfying preliminary results in both primary and salvage lymphadenectomy, allowing to discriminate between pathological and non-pathological nodes with high accuracy, although prospective studies with larger cohorts are needed to further validate this surgical approach. The potential of PSMA-targeted SPECT/CT has not been fully explored yet, but it might represent a relatively cost-effective alternative to PSMA PET/CT in limited resource environments. In this perspective, the implementation of novel SPECT technologies or algorithms, such as semiconductor-ionization detectors or resolution recovery reconstruction, will be topic of future investigation.

KEYWORDS:

• Prostate cancer
• theranostics
• single photon emission tomography
• positron emission computed tomography
• precision medicine
• targeted therapy

Article highlights

• Prostate-Specific Membrane Antigen (PSMA) represents a relevant target associated with prostate cancer (PC) and has been entailed for approaches combining diagnosis and therapy (‘theranostics’).

• Some small molecules, based on the lysine-urea-glutamate motif, exhibit inhibiting properties with respect to PSMA-extracellular enzymatic domain. These compounds, namely PSMA-inhibitors, have been labeled with radionuclides emitting energy suitable for imaging or therapy.

• PSMA-inhibitors labeled with gamma-emitting radionuclides, such as ¹¹¹In or ^99mTc, have been synthesized and investigated as imaging agents for single photon emission computed tomography (SPECT/CT) and radioguided surgery (RGS).

• RGS with gamma-emitting PSMA tracers has provided satisfying preliminary results both in patients submitted to lymphadenectomy during prostatectomy or as salvage therapy in patients with recurrence, showing high accuracy for discriminating pathological vs non-pathological nodes, also identifying additional localizations with respect to pre-operative PSMA-PET.

• PSMA SPECT/CT showed good accuracy for the detection of PC lesions both at staging and in patients submitted to loco-regional or systemic treatments, although with lower detection rate, especially on region-based analysis, when compared to PSMA-PET/CT, and sometimes requiring multi-day acquisition protocols not comfortable for patients.

• The potential of some technology innovations, such as large field-of-view handheld gamma-cameras, or novel detector and reconstruction algorithms for imaging and RGS with PSMA-targeted will be topic of future investigations.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Author contributions

L.F. and O.S. designed the review study; S.N. and B.P. performed the literature research and data extraction; L.F., V.F. and B.P. wrote the paper; G.D.V. and A.S. supervised the paper.

Additional information

Funding

This paper was not funded.