Phase III Multicentre Prospective Comparative Study of Detection Rate of 18F-JK-PSMA-7 and of 18F-fluorocholine in Patients With Biochemical Recurrence of Prostate Cancer After Previous Treatment With Curative Intent

The present study in patients with Prostate cancer and biochemical failure after surgery and/or radical-postoperative Radio Therapy (RT) will evaluate if PET/CT with 18F-JK-PSMA-7 compared to PET-CT 18F-Choline is able to identify the early pattern of biochemical recurrence and/or metastatic sites, so that the patient could be better managed, with a benefit in survival.

Start Date19 Dec 2022

Sponsor / Collaborator

ITEL Telecomunicazioni SRL

CTRI/2022/04/042050 / Not yet recruitingNot Applicable

Preoperative localisation of parathyroid adenoma in patients with primary hyperparathyroidism with 4D-CT versus 18F-fluorocholine PET CT: A pilot randomised controlled trial.

Start Date01 May 2022

Sponsor / Collaborator-

NCT04965454 / RecruitingPhase 2

Clinical Trial of Biomarkers for Predicting Immunotherapy Response in Hepatocellular Carcinoma

This prospective clinical trial will evaluate PET/CT and genomic liquid biopsy based biomarkers as predictors of clinical therapeutic response to immune-checkpoint inhibitor (ICI) therapy for patients with inoperable hepatocellular carcinoma (HCC). The primary objective of this diagnostic trial is to assess the accuracy of pre-treatment fluorine-18 (18F-) fluorocholine (FCH) PET/CT for predicting a lack of objective response (LOR) after 16 weeks of ICI therapy.

Start Date28 Mar 2022

Sponsor / Collaborator

The Queen's Medical Center

[+1]

100 Clinical Results associated with 18F-Fluoromethylcholine

100 Translational Medicine associated with 18F-Fluoromethylcholine

100 Patents (Medical) associated with 18F-Fluoromethylcholine

Literatures (Medical) associated with 18F-Fluoromethylcholine

01 Sep 2023·European journal of nuclear medicine and molecular imaging

[¹⁸F]DCFPyL PET/CT versus [¹⁸F]fluoromethylcholine PET/CT in Biochemical Recurrence of Prostate Cancer (PYTHON): a prospective, open label, cross-over, comparative study.

Article

Author: Mitjavila, Mercedes ; Mahmoud, Sinan Ben ; Oprea-Lager, Daniela-Elena ; Hodolic, Marina ; Vallejo-Casas, Juan Antonio ; Vierasu, Irina ; Tissot, Hubert ; Vander Borght, Thierry ; Gauthé, Mathieu ; Drouet, Clément ; Merlin, Charles ; Boos, Evelyne ; García Vicente, Ana Maria ; García-Cañamaque, Lina ; Maksud, Philippe ; Bailliez, Alban ; Robin, Philippe ; Blanc-Durand, Paul ; Rodríguez-Fernández, Antonio ; Tamayo, Pilar ; Gontier, Eric ; Chossat, Florence ; Olivier, Pierre ; Rousseau, Caroline ; Bouyeure, Anne-Charlotte

PURPOSE:

Primary objective was to compare the per-patient detection rates (DR) of [¹⁸F]DCFPyL versus [¹⁸F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM).

METHODS:

This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [¹⁸F]DCFPyL (investigational medicinal product) or [¹⁸F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [¹⁸F]DCFPyL and [¹⁸F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs.

RESULTS:

A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [¹⁸F]DCFPyL- and/or [¹⁸F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [¹⁸F]DCFPyL- compared to [¹⁸F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [¹⁸F]DCFPyL- and [¹⁸F]fluoromethylcholine -PET/CT, respectively). [¹⁸F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [¹⁸F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed.

CONCLUSIONS:

The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [¹⁸F]DCFPyL compared to [¹⁸F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [¹⁸F]DCFPyL was safe and well tolerated.

04 Apr 2023·Circulation

Gut Microbiota-Derived Trimethylamine N-Oxide Contributes to Abdominal Aortic Aneurysm Through Inflammatory and Apoptotic Mechanisms.

Article

Author: Mani, Kevin ; Cameron, Scott J ; Björck, Martin ; Biddinger, Sudha ; Hazen, Stanley L ; Bhandari, Rohan ; Tranter, Michael ; Coughlin, Taylor M ; Sangwan, Naseer ; Benson, Tyler W ; Li, Xinmin S ; Wanhainen, Anders ; Helsley, Robert N ; Conrad, Kelsey A ; Wadding-Lee, Caris ; Stone, Timothy ; Brown, J Mark ; Owens, A Phillip ; Schugar, Rebecca C ; Brooks, Michael ; Buffa, Jennifer A ; Tang, W H Wilson ; Russell, Hannah M ; Pascual, Crystal ; Fleifil, Salma ; Wang, Zeneng ; Ademoya, Akiirayi

BACKGROUND:

Large-scale human and mechanistic mouse studies indicate a strong relationship between the microbiome-dependent metabolite trimethylamine N-oxide (TMAO) and several cardiometabolic diseases. This study aims to investigate the role of TMAO in the pathogenesis of abdominal aortic aneurysm (AAA) and target its parent microbes as a potential pharmacological intervention.

METHODS:

TMAO and choline metabolites were examined in plasma samples, with associated clinical data, from 2 independent patient cohorts (N=2129 total). Mice were fed a high-choline diet and underwent 2 murine AAA models, angiotensin II infusion in low-density lipoprotein receptor-deficient (Ldlr^-/-) mice or topical porcine pancreatic elastase in C57BL/6J mice. Gut microbial production of TMAO was inhibited through broad-spectrum antibiotics, targeted inhibition of the gut microbial choline TMA lyase (CutC/D) with fluoromethylcholine, or the use of mice genetically deficient in flavin monooxygenase 3 (Fmo3^-/-). Finally, RNA sequencing of in vitro human vascular smooth muscle cells and in vivo mouse aortas was used to investigate how TMAO affects AAA.

RESULTS:

Elevated TMAO was associated with increased AAA incidence and growth in both patient cohorts studied. Dietary choline supplementation augmented plasma TMAO and aortic diameter in both mouse models of AAA, which was suppressed with poorly absorbed oral broad-spectrum antibiotics. Treatment with fluoromethylcholine ablated TMAO production, attenuated choline-augmented aneurysm initiation, and halted progression of an established aneurysm model. In addition, Fmo3^-/- mice had reduced plasma TMAO and aortic diameters and were protected from AAA rupture compared with wild-type mice. RNA sequencing and functional analyses revealed choline supplementation in mice or TMAO treatment of human vascular smooth muscle cells-augmented gene pathways associated with the endoplasmic reticulum stress response, specifically the endoplasmic reticulum stress kinase PERK.

CONCLUSIONS:

These results define a role for gut microbiota-generated TMAO in AAA formation through upregulation of endoplasmic reticulum stress-related pathways in the aortic wall. In addition, inhibition of microbiome-derived TMAO may serve as a novel therapeutic approach for AAA treatment where none currently exist.

01 Aug 2015·Journal of nuclear medicine : official publication, Society of Nuclear MedicineQ1 · MEDICINE

Prospective Comparison of ¹⁸F-Fluoromethylcholine Versus ⁶⁸Ga-PSMA PET/CT in Prostate Cancer Patients Who Have Rising PSA After Curative Treatment and Are Being Considered for Targeted Therapy

Q1 · MEDICINE

Article

Author: Fogarty, Gerald ; Kneebone, Andrew ; Jagavkar, Raj ; Tarlinton, Lisa ; Tang, Reuben ; Hickey, Adam ; Morigi, Joshua J ; Fanti, Stefano ; Nguyen, Quoc ; Hruby, George ; van Leeuwen, Pim J ; Emmett, Louise ; Stricker, Phillip D ; Ho, Bao

METHODS:

A sample of men with a rising PSA level after treatment, eligible for targeted treatment, was prospectively included. Patients on systemic treatment were excluded. (68)Ga-PSMA, (18)F-fluoromethylcholine PET/CT, and diagnostic CT were performed sequentially on all patients between January and April 2015, and the images were assessed by masked, experienced interpreters. The findings and their impact on management were documented, together with the results of histologic follow-up when feasible.

RESULTS:

In total, 38 patients were enrolled. Of these, 34 (89%) had undergone radical prostatectomy and 4 (11%) had undergone radiation treatment. Twelve (32%) had undergone salvage radiation treatment after primary radical prostatectomy. The mean PSA level was 1.74 ± 2.54 ng/mL. The scan results were positive in 26 patients (68%) and negative with both tracers in 12 patients (32%). Of the 26 positive scans, 14 (54%) were positive with (68)Ga-PSMA alone, 11 (42%) with both (18)F-fluoromethylcholine and (68)Ga-PSMA, and only 1 (4%) with (18)F-fluoromethylcholine alone. When PSA was below 0.5 ng/mL, the detection rate was 50% for (68)Ga-PSMA versus 12.5% for (18)F-fluoromethylcholine. When PSA was 0.5-2.0 ng/mL, the detection rate was 69% for (68)Ga-PSMA versus 31% for (18)F-fluoromethylcholine, and when PSA was above 2.0, the detection rate was 86% for (68)Ga-PSMA versus 57% for (18)F-fluoromethylcholine. On lesion-based analysis, (68)Ga-PSMA detected more lesions than (18)F-fluoromethylcholine (59 vs. 29, P < 0.001). The tumor-to-background ratio in positive scans was higher for (68)Ga-PSMA than for (18)F-fluoromethylcholine (28.6 for (68)Ga-PSMA vs. 9.4 for (18)F-fluoromethylcholine, P < 0.001). There was a 63% (24/38 patients) management impact, with 54% (13/24 patients) being due to (68)Ga-PSMA imaging alone. Histologic follow-up was available for 9 of 38 patients (24%), and 9 of 9 (68)Ga-PSMA-positive lesions were consistent with prostate cancer ((68)Ga-PSMA was true-positive). The lesion positive on (18)F-fluoromethylcholine imaging and negative on (68)Ga-PSMA imaging was shown at biopsy to be a false-positive (18)F-fluoromethylcholine finding ((68)Ga-PSMA was true-negative).

CONCLUSION:

In patients with biochemical failure and a low PSA level, (68)Ga-PSMA demonstrated a significantly higher detection rate than (18)F-fluoromethylcholine and a high overall impact on management.

News (Medical) associated with 18F-Fluoromethylcholine

21 Jul 2023

·www.globenewswire.com

Curium Announces Publication of [18F]DCFPyL Versus [18F]Fluoromethylcholine Results From European Phase III Study (PYTHON Trial)

PARIS, July 21, 2023 (GLOBE NEWSWIRE) -- Curium, a world leader in nuclear medicine, announced today the publication of the results of its European, multicenter, prospective cross-over clinical trial which compared [18F] piflufolastat ([18F]DCFPyL) versus [18F]fluoromethylcholine PET/CT in patients with first biochemical recurrence of prostate cancer. The results of the PYTHON trial were published online ahead of print in the European Journal of Nuclear Medicine and Molecular Imaging in June 2023. Today’s announcement follows the May 2023 recommendation by the Committee for Medicinal Products for Human Use of the European Medicines Agency to grant a marketing authorization for PYLCLARI® (piflufolastat (18F)) indicated for the detection of prostate-specific membrane antigen (PSMA) positive lesions with positron emission tomography (PET) in patients with prostate cancer – based on the Phase III PYTHON clinical trial conducted in Europe and the Phase III OSPREY and CONDOR clinical trials conducted in the U.S. Dr. Daniela E. Oprea-Lager| Assoc. Professor in Nuclear Medicine, MD PhD, Amsterdam UMC (lead author of the PYTHON Manuscript submitted to the European Journal of Nuclear Medicine and Molecular Imaging) commented: “Adequate restaging of patients with biochemically relapsed prostate cancer is essential for guiding clinicians on how to choose the optimal treatment strategy with the maximum benefit for the patients. PYTHON trial demonstrates the superiority of [18F]DCFPyL above [18F]fluoromethylcholine PET/CT paving the way towards individualized therapy.” Sakir Mutevelic, MD, MSc, Chief Medical Officer at Curium commented: “[18F]fluoromethylcholine has been the current approved and established standard for PET/CT imaging of prostate cancer in Europe, and the publication of this manuscript validates our success in developing new diagnostic imaging solutions – as we continue on our journey to redefine the experience of cancer through our trusted legacy in nuclear medicine.” In the U.S., piflufolastat (18F) was approved by the Food and Drug Administration (FDA) in May 2021 and is commercially available as PYLARIFY® and sold by Lantheus. The PYTHON publication in European Journal of Nuclear Medicine and Molecular Imaging can be found here. PYTHON Study The PYTHON Study (NCT04734184) was a Phase III, European, multicenter, prospective cross-over trial, to evaluate and compare the detection rates, impact on patient management and safety proﬁles of [18F]DCFPyL and [18F]fluoromethylcholine, in patients with first biochemical recurrence after initial definitive therapy with curative intent. This study successfully met the primary endpoint. About PYLARIFY® (piflufolastat F 18, also known as [18F]DCFPyL) Injection PYLARIFY® (piflufolastat F 18) injection (also known as [18F]DCFPyL or PyL) is a fluorinated small molecule PSMA-targeted PET imaging agent that enables visualization of lymph nodes, bone and soft tissue metastases to determine the presence or absence of recurrent and/or metastatic prostate cancer. For men with prostate cancer, PYLARIFY PET combines the accuracy of PET imaging, the precision of PSMA targeting and the clarity of an F 18 radioisotope for superior diagnostic performance. The recommended PYLARIFY dose is 333 MBq (9 mCi) with an acceptable range of 296 MBq to 370 MBq (8 mCi to 10 mCi), administered as a bolus intravenous injection.1-6 PYLARIFY is FDA-approved and commercialized in the U.S. by Lantheus. The European rights were licensed by Curium from Progenics, a Lantheus company, in 2019. About CuriumCurium is a world leader in nuclear medicine. We develop, manufacture, and distribute world-class radiopharmaceutical products to help patients around the globe. Our proven heritage combined with a pioneering approach are the hallmarks to deliver innovation, excellence, and unparalleled service. With manufacturing facilities across Europe and the United States, Curium delivers SPECT, PET and therapeutic radiopharmaceutical solutions for life-threatening diseases to over 14 million patients annually. The name ‘Curium’ honors the legacy of pioneering radioactive materials researchers Marie and Pierre Curie, after whom the radioactive element curium was named and emphasizes our focus on nuclear medicine. To learn more, visit www.curiumpharma.com For more information:Ross BethellVP, Head of Global Communicationscommunications@curiumpharma.com 1Tan N, Oyoyo U, Bavadian N, et al. PSMA-targeted radiotracers versus 18F fluciclovine for the detection of prostate cancer biochemical recurrence after definitive therapy: a systematic review and meta-analysis. Radiology. 2020;296:44-55. doi:10.1148/radiol.20201916892Mena et al. 18 F-DCFPyL PET/CT Imaging in Patients with Biochemically Recurrent Prostate Cancer After Primary Local Therapy J Nucl Med 2020 Jun;61(6):881-889. doi: 10.2967/jnumed.119.234799. Epub 2019 Nov 1.3Alipour et al. Guiding management of therapy in prostate cancer: time to switch from conventional imaging to PSMA PET? Ther Adv Med Oncol. 2019; 11: 1758835919876828.4Werner et al 18F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging Theranostics 2020; 10(1):1-16. doi:10.7150/thno.37894.5Petersen LJ, Zacho HD. PSMA PET for primary lymph node staging of intermediate and high-risk prostate cancer: an expedited systematic review. Cancer Imaging. 2020;20(1):1-8. doi:10.1186/s40644-020-02906PYLARIFY® [package insert]. North Billerica, MA: Progenics Pharmaceuticals, Inc., a Lantheus company

Phase 3Drug ApprovalClinical ResultRadiation Therapy

100 Deals associated with 18F-Fluoromethylcholine

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Phase 3	CA	The Jewish General Hospital	01 Sep 2016
Hepatocellular Carcinoma	Phase 3	TW	National Taiwan University Hospital	01 Feb 2014

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03764007 (CTgov)	Phase 2/3	Parathyroid Adenoma \| Hyperparathyroidism, Primary	98	Positron Emission Tomography (PET)+18F-Fluorocholine	vjmymqmyro(qeermwvzpz) = ccpsffiqdi dqhcsasnoh (mfxuzdvimi, qbqhnxrmrc - woocjxxghb) View more	-	19 Oct 2021
NCT02397408 (CTgov)	Phase 2	Prostatic Cancer	18	Positron Emission Tomography (PET) / Magnetic Resonance Imaging (MRI)+Carbon C 11 Choline+Fluorine F 18 Choline	wsrdilakjv(ylnbprhugi) = tpikavlarv raisveoipy (jhorzafnvq, terhhflcxi - qjnpeyvfdk) View more	-	19 Nov 2020
NCT01395030 (CTgov)	Phase 2	Hepatocellular Carcinoma \| Liver Cancer	64	Computed Tomography+18F-fluoromethylcholine	dnndekmkpd(acftjatafl) = wumppsbhoh zpddbwdgvf (deabawlwfi, lofwfooljt - arndlupfur) View more	-	26 Sep 2018
NCT00928252 (CTgov)	Phase 1/2	Castration-Resistant Prostatic Cancer	25	IV fluorine-18 labeled methylcholine before PET/CT	eoqibeaznq(hoogexrigi) = vugnjorfrl rntzlpjafi (dcogyonimw, mgenmyipcm - ygupokdllh) View more	-	14 Aug 2017
Pubmed \| Eur J Nucl Med Mol Imaging	Not Applicable	Hyperparathyroidism, Primary	24	18F-Fluorocholine	nyiphqgrre(ceuezjwjcl) = vmeqqhqpzz vssxffffaq (nqcsteptjg ) View more	-	01 Nov 2014
Pubmed \| Eur J Nucl Med Mol Imaging	Not Applicable	Hyperparathyroidism, Primary	24	(99m)Tc-sestaMIBI dual-phase imaging	nyiphqgrre(ceuezjwjcl) = zjvihhfsum vssxffffaq (nqcsteptjg ) View more	-	01 Nov 2014

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