The evolving role of [18F]DCFPyL (Pylarify) PET/CT in the management of Prostate Cancer

Introduction: Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is gaining popularity for the management of metastatic prostate cancer (PC). It has several advantages in locating potential disease sites, in vivo quantification of the therapeutic target, and as a theranostic agent. PSMA ligands labeled with 18F, 68Ga, 177Lu, and 225Ac radionuclides have been employed with encouraging results. We aim to explore the role of [18F]DCFPyL (also known as piflufolastat F18 or Pylarify), an 18F-labeled PSMA agent, for molecular imaging of metastatic PC.

Methods: In order to carry out a thorough literature analysis, studies indexed by Pubmed and Google Scholar were searched using the keywords "prostate cancer," "PSMA," "[18F]DCFPyL," "Piflufolastat F18," and "Pylarify." Highly cited articles were reviewed to evaluate the usefulness of [18F]DCFPyL PET/CT in the management of prostate cancer.

Results: After approval by the U.S. Food and Drug Administration, the use of [18F]DCFPyL PET/CT for the detection of metastatic prostate cancer has been increasing in the United States. It has shown various advantages over standard diagnostic modalities. [18F]DCFPyL PET/CT has demonstrated a superior detection rate than conventional imaging modalities for the detection of diseased sites via initial lesion-by-lesion analysis. When [18F]DCFPyL was compared with the bone-seeking PET agent 18F-NaF, sensitivities were similar for lesions in the bone; however, [18F]DCFPyL PET/CT had the extra advantage of providing information on soft tissues. It suggests that there might not be any added benefit to performing 18F-NaF PET/CT when a PSMA-targeted PET/CT has already been performed.

Studies comparing [18F]DCFPyL and 68Ga-PSMA in PC patients with the biochemically recurrent illness have demonstrated [18F]DCFPyL to have a higher detection rate and a better tumor-to-background ratio. Additionally, due to the longer half-life of 18F, [18F]DCFPyL has been useful for inter-center dissemination and delayed imaging techniques, such as those that use furosemide to increase pelvic contrast in order to find probable PSMA-avid lymph node metastases. Nonetheless, its physical characteristics, like decreased positron energy, make it possible to improve image quality and reduce noise significantly.

Among the clinically proven 18F-labeled agents, when [18F]PSMA-1007 and [18F]DCFPyL were compared head-to-head in a semi-quantitative analysis, both radiotracers detected identical lesions with no noticeable differences. However, normal organ uptake was significantly different. The non-urinary excretion of [18F]PSMA-1007 may allow for a more accurate read-out of the local recurrence of pelvic lymph node metastases. In contrast, the lower liver background of [18F]DCFPyL may ensure higher interpretative certainty for hepatic involvement. Similarly, [18F]DCFPyL PET/CT has demonstrated more consistent findings than [18F]PSMA-1007 PET/CT in the skeleton, and hence, it increases the agreement rate for [18F]DCFPyL PET/CT for detecting bone lesions. In addition to this, numerous important trials on [18F]DCFPyL PET/CT have given solid evidence of its role in staging, restaging, change in management, and response assessment.

Conclusions: [18F]DCFPyL PET/CT has been found to be more efficacious than conventional imaging modalities and PSMA ligands labeled with other radionuclides in the management of prostate cancer. However, further studies are required to evaluate its specific uses in clinical settings.