¹⁸F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

Abstract

Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with 68Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from 68Ga- to 18F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite 68Ge/68Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, 18F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, 18F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging 18F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available 18F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.

18F-DCFPyL PET/CT in Patients with Subclinical Recurrence of Prostate Cancer: Effect of Lesion Size, Smoothing Filter, and Partial-Volume Correction on PROMISE Criteria

“…The most widely used PSMA radiotracer is 68 Ga-PSMA-11 (also named 68 Ga-PSMA-HBED-CC). Recently introduced 18 F-labelled PSMA tracers have the advantage of cyclotron production, enabling multiple doses from a single formulation, longer half-life of 18 F compared to 68 Ga, facilitating shipping of the tracer to off-site facilities, lower energy and shorter positron range, allowing for higher image resolution (2). One such tracer is 18 F-DCFPyL ( Table 1].…”

68Ga-PSMA-11 PET/MRI: determining ideal acquisition times to reduce noise and increase image quality

“…In addition to 68 Ga-labelled PSMA radiotracers, 18F-labelled PSMA imaging agents have also become more numerous and can offer potential benefits over 68 Ga-labelled tracers as well. Unlike 68 Ga agents, 18F agents have a higher potential for delivery to smaller hospitals and PET centers [21]. Furthermore, cyclotron-based synthesis of 18F imaging agents allows for synthesis of higher activity, and the lower positron energies of 18F may result in sharper imaging [21].…”

“…Unlike 68 Ga agents, 18F agents have a higher potential for delivery to smaller hospitals and PET centers [21]. Furthermore, cyclotron-based synthesis of 18F imaging agents allows for synthesis of higher activity, and the lower positron energies of 18F may result in sharper imaging [21]. It is possible that in the near future, cyclotron production of 68 Ga may allow for increased administered doses of 68 Ga-PSMA-11.…”

Prostate Cancer Theranostics - An Overview

“…Multiple doses of Fluorine-18 radiolabeled inhibitor are available at institutions with a medical cyclotron, with the ability to ship agent at greater distances. Lower upfront costs are required for Gallium-68 isolation on a 68 Ge/ 68 Ga generator system, however fewer doses are produced with lower specific activity, and decreased resolution (46)(47)(48)(49).…”