[⁶⁸Ga]PSMA-11 for positron emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA)-positive lesions in men with prostate cancer

ABSTRACT

Introduction

Theranostics targeting prostate-specific membrane antigen (PSMA) represent a new targeted approach for prostate cancer care that combines diagnostic and therapeutic radiopharmaceuticals to diagnose and treat the disease. Positron emission tomography (PET) is the imaging method of choice and several diagnostic radiopharmaceuticals for quantifying PSMA have received FDA approval and are in clinical use. [⁶⁸Ga]Ga-PSMA-11 is one such imaging agent and the focus of this article. One beta-emitting radioligand therapy ([¹⁷⁷Lu]Lu-PSMA-617) has also received FDA approval for prostate cancer treatment, and several other alpha- and beta-emitting radioligand therapies are in clinical trials.

Areas covered

Theranostics targeting PSMA in men with prostate cancer are discussed with a focus on use of [⁶⁸Ga]Ga-PSMA-11 for imaging PSMA-positive lesions in men with prostate cancer. The review covers [⁶⁸Ga]Ga-PSMA-11 manufacture, current regulatory status, comparison of [⁶⁸Ga]Ga-PSMA-11 to other imaging techniques, clinical updates, and emerging applications of artificial intelligence for [⁶⁸Ga]Ga-PSMA-11 PET.

Expert opinion

[⁶⁸Ga]Ga-PSMA-11 is used in conjunction with a PET/CT scan to image PSMA positive lesions in men with prostate cancer. It is manufactured by chelating precursor with⁶⁸Ga, either from a generator or cyclotron, and has regulatory approval around the world. It is widely used clinically in conjunction with radioligand therapies like [¹⁷⁷Lu]Lu-PSMA-617.

KEYWORDS:

• PET
• theranostics
• gallium-68
• PSMA
• prostate cancer
• artificial intelligence

Article highlights

• Prostate specific membrane antigen (PSMA) is overexpressed in the majority of prostate cancer lesions, making it a compelling target for prostate cancer theranostics, the same (or very similar) molecules labeled with therapeutic and diagnostic radionuclides.

• PSMA is expressed in numerous other significant cancers, suggesting potential widespread theranostic applications beyond prostate cancer.

• A commonly used PSMA-targeting diagnostic agent is [⁶⁸Ga]Ga-PSMA-11 (gallium Ga 68 gozetotide injection).

• [⁶⁸Ga]Ga-PSMA-11 is FDA approved for PET imaging of positive lesions in men with prostate cancer that i) have suspected metastasis who are candidates for initial definitive therapy, ii) have suspected recurrence based on elevated serum prostate-specific antigen (PSA) levels, and/or iii) for selection of patients with metastatic prostate cancer, for whom ¹⁷⁷Lu-PSMA-617 (Pluvicto, lutetium Lu 177 vipivotide tetraxetan) PSMA-directed therapy is indicated.

• [⁶⁸Ga]Ga-PSMA-11 is approved as a new drug (UCLA/UCSF), and two kits are also approved for preparation of [⁶⁸Ga]Ga-PSMA-11: Illucix (Telix) and Locametz (Novartis).

• [⁶⁸Ga]Ga-PSMA-11 can be prepared using both generator-derived and cyclotron-produced ⁶⁸Ga.

• A number of professional societies, including the Society of Nuclear Medicine and Molecular Imaging, have developed consensus guidelines and appropriate use criteria for PSMA PET.

• On clinicaltrials.gov, >200 studies are utilizing [⁶⁸Ga]Ga-PSMA-11 PET/CT, including studies of the imaging agent itself, as well as its prognostic value to various strategies for managing prostate cancer, and to support development of PSMA-targeting radioligand therapies for use alone or in combination with other therapeutic approaches.

• Artificial intelligence has been applied to [⁶⁸Ga]Ga-PSMA-11 PET/CT images for the detection, classification, prediction and prognostication of prostate cancer, as well as evaluation of patients for Pluvicto therapy.

Declaration of interest

PJH Scott has received funding from GE Healthcare, and owns shares in GE Healthcare, Telix Pharmaceuticals, Lantheus and Novartis. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737159.2024.2383439

Additional information

Funding

This paper was not funded.