18F-Piflufolastat is a radiotracer used in positron emission tomography (PET) imaging to visualize prostate-specific membrane antigen (PSMA) expression in prostate cancer cells. PSMA is a transmembrane protein that is highly expressed in prostate cancer cells, making it a valuable target for imaging and therapy.
18F-Piflufolastat is a small molecule inhibitor that binds specifically to PSMA, allowing for the detection of prostate cancer cells with high sensitivity and specificity. The radiotracer is labeled with the positron-emitting isotope fluorine-18, which allows for the visualization of PSMA expression in real-time using PET imaging.
Clinical studies have shown that 18F-Piflufolastat PET imaging is highly effective in detecting primary and metastatic prostate cancer lesions, as well as monitoring treatment response and disease progression. The radiotracer has also been shown to have a favorable safety profile, with minimal side effects reported in patients.
Overall, 18F-Piflufolastat is a promising tool for the non-invasive imaging of prostate cancer, providing valuable information for treatment planning and monitoring in patients with this disease.
Description
18F-Piflufolastat (previously 18F-DCFPyL, also called PyL™ or 18F-PyL) is a new generation PSMA-imaging tracer developed at Johns Hopkins Institute in Baltimore MD, USA. It is an improvement of a family of peptides developed in this university in the past five years. It was exclusively worldwide licensed by Progenics Pharmaceuticals in August 2015. In October 2015, Cyclotek licensed 18F-DCFPyL for Australia and New Zealand. In January 2019, Curium signed an exclusive agreement with Progenics for the development of this tracer in Europe. Progenics was acquired by Lantheus in October 2019. Lantheus filed an NDA with a priority review request to the FDA in September 2020. Priority review was granted in December 2020 and MA was obtained from FDA by May 2021. 18F-Piflufolastat will be sold in the USA under the brand name Pylarify®.
In December 2020, Point Biopharma announced it will use 18F-DCFPyL in its phase III clinical trial for patients with mCRPC.
Clinical applications
18F-DCFPyL is a PET imaging tracer targeting primary and metastasized prostate cancer alike all PSMA-imaging agents that have been developed since 2010. 18F-DCFPyL is also explored in Clear Cell Renal-cell carcinoma and gynecological cancers (ovarian), as well as, more recently, in metastasized breast cancer.
US MA obtained from the FDA as a diagnostic agent indicated for PET of PSMA positive lesions in men with prostate cancer with (a) suspected metastasis who are candidates for initial definitive therapy or (b) suspected recurrence based on elevated serum PSA level.
Availability
18F-DCFPyL became available in parts of the US mid-Atlantic and southern regions and availability was expected to rapidly expand across the US over the end of year 2021.
Stage of development
18F-DCFPyL was under clinical evaluation (Phase I/II) with CPDC in Canada since end of 2015. It has proven to be safe with a human biodistribution as expected. Comparative clinical studies with 68Ga-PSMA-11 have also been performed on 14 patients, which did provide high quality images with excellent sensitivity.The tracer is considered as ‘a highly promising alternative to 68Ga-PSMA-11 for PSMA-PET/CT imaging in relapsed prostate cancer. Several additional trials have been initiated with this tracer.1
The first patient of the Phase II/III trial was included in December 2016. This study enrolled 266 patients and was completed by June 2018.2
More than 68 studies involving 18F-DCFPyL are reported in the US clinical trials data base among which 14 have been initiated in the course of the year 2020 and the first half of 2021. All of them are evaluating the potential of the tracer in prostate cancer, but two in renal cancer and two others in gynecological cancers. The most recently initiated study is evaluating this tracer in patients with breast cancer.3
A Phase III study sponsored by Progenics and enrolling up to 1,500 patients was started in June 20184 and results were used in the NDA dossier filed at the US FDA The estimated recruitment completion date is June 2023 while the estimated study date has been fixed one year later. The most recent publication is to be found under.5 Another Phase III trial (CONDOR trial)6 was initiated in November 2018. It was aiming at evaluating the diagnostic performance and safety of 18F-DCFPyL imaging in 200 patients with suspected recurrence of prostate cancer who have negative or equivocal findings on conventional imaging (i.e., Axumin, Choline PET, CT/MR and/or bone scan). This trial was completed in December 2019 and Progenics announced positive top line results. Based on these results, Progenics/Lantheus submitted an NDA to the FDA in the second half of 2020 and MA for the US was obtained in May 2021.
Comments
18F-Piflufolastat (DCFPyL) obtained marketing authorization in the US shortly after MA was granted to two universities (local availability) for 68Ga-PSMA-11. Due to their target and tracer biological profile, these two molecules will probably take over the market of 18F-Fluciclovine. Actually, the real competition between companies will start when 68Ga-PSMA-11 will obtain its MA. There is only a small difference in terms of imaging quality for both molecules and, therefore, the real competition will take place in terms of availability and price. While the Fluorinated tracer will need the (expensive) implementation of dedicated production sites, the Gallium-labelled tracer will need to guarantee access to 68Ge/68Ga generators, an issue which is not yet completely solved. Eventually, if availability issues will be solved, the price competition will remain on the side of the gallium analogue, as implementing sites to cover the full territory will remain an expensive game.
Both tracers will also have to compete with the 99mTc-labeled analogue when available, as this tracer will definitely be the cheapest.
Sales figures during the year 2022 will show which product/company will be in the most favorable situation.
- https://www.clinicaltrials.gov/ct2/show/NCT02825875 ; Study of the clinical utility of PSMA imaging in the evaluation of men with prostate cancer
https://www.clinicaltrials.gov/ct2/show/NCT02899312 : PSMA PET/CT for Prostate Cancer
https://www.clinicaltrials.gov/ct2/show/NCT02793284 : Advanced prostate imaging of recurrent cancer after radiotherapy
https://www.clinicaltrials.gov/ct2/show/NCT03149861 : Detection of clinically significant prostate cancer with 18F-DCFPyL PET/MR
https://www.clinicaltrials.gov/ct2/show/NCT03001895: Correlation between SUV on 18F-DCFPyL PET/CT and Gleason score in prostate cancer
https://www.clinicaltrials.gov/ct2/show/NCT02691169 : Integrated 18F-labeled PSMA Project
https://www.clinicaltrials.gov/ct2/show/NCT02856100 : Comparison of PSMA-based 18F-DCFPyL PET/CT to conventional imaging in the evaluation of patients with castration-resistant prostate cancer ↩︎ - https://www.clinicaltrials.gov/ct2/show/NCT02981368 : Study of 18F-DCFPyL PET/CT imaging in patients with prostate cancer (OSPREY) ↩︎
- https://clinicaltrials.gov/ct2/show/NCT04573231 – Evaluation of PSMA in HER2- AR+ Metastatic Breast Cancer ↩︎
- https://www.clinicaltrials.gov/ct2/show/NCT03459820 : 18F-DCFPyL PET/CT in Prostate Cancer ↩︎
- http://jnm.snmjournals.org/content/early/2019/04/11/jnumed.119.226381.abstract ↩︎
- https://clinicaltrials.gov/ct2/show/NCT03739684 ↩︎