[68Ga]Ga-PSMA Versus [18F]PSMA Positron Emission Tomography/Computed Tomography in the Staging of Primary and Recurrent Prostate Cancer. A Systematic Review of the Literature

CONTEXT: In the past 10 yr, several agents based on prostate-specific membrane antigen (PSMA) for positron emission tomography imaging have been introduced in clinical practice for the management of patients with prostate cancer (PCa).

OBJECTIVE: To analyse the available data in the literature to clarify the advantages and disadvantages of [68Ga]Ga-PSMA and [18F]PSMA in different settings of PCa.

EVIDENCE ACQUISITION: A systematic literature search was made by using two main databases. Only studies published in the past 5 yr (2016-2021) in the English language with >20 enrolled patients were selected. Two reviewers independently appraised each article using a standard protocol. All the studies were analysed using a modified version of the Critical Appraisal Skills Programme checklist for diagnostic test studies.

EVIDENCE SYNTHESIS: The systematic evaluation was made in 12 papers. Based on the quality assessment, the analysed studies demonstrated different methodologies. Three papers focused on the head-to-head comparison between 18F- and [68Ga]Ga-PSMA (n = 123 patients). A matched-pair comparison between 18F- and [68Ga]Ga-PSMA was reported in three papers, including 715 patients. The remaining papers used indiscriminately either 68Ga-PSMA or [18F]PSMA (n = 1.157 patients). [18F]PSMA-1007 is superior to [68Ga]Ga-PSMA-11 for the identification of local recurrence (less activity close to the bladder for [18F]PSMA-1007). Nonspecific/equivocal bone lesions are often recognised at [18F]PSMA-1007. [18F]DCFPyL is more reproducible for the identification of lymph nodes, and it shows fewer equivocal skeletal lesions and higher inter-reader agreement on skeletal lesions.

CONCLUSIONS: Despite a large body of literature on PSMA radiopharmaceutical agents labelled with 68Ga or 18F, there are limited head-to-head or matched-pair comparative data. Certain clinical indications could trigger a preference, whilst caution is needed in interpreting potential false-positive findings, especially with [18F]PSMA-1007. Given the excellent performance of all accessible radiopharmaceuticals, the availability of specific tracers will likely guide choice.

PATIENT SUMMARY: In this systematic review, we analysed the currently available literature focused on [68Ga] and [18F]-labelled prostate-specific membrane antigen. Our purpose is to identify which tracers would be correctly employed for the management of patients with prostate cancer.