Phase IIa clinical study of [18F]fluciclovine: efficacy and safety of a new PET tracer for brain tumors

Kondo, Akihide; Ishii, Hisato; Aoki, Shigeki; Suzuki, Mitsuaki; Nagasawa, Hidekazu; Kubota, Keiichi; Minamimoto, Ryogo; Arakawa, Atsushi; Tominaga, Masato; Arai, Hajime

doi:10.1007/s12149-016-1102-y

Cited by 70 publications

(66 citation statements)

References 32 publications

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“…This, and the fact that [ 18 F]fluciclovine is distributed throughout the entire body, prevent the [ 18 F]fluciclovine plasma concentration from reaching levels required for inhibition. Therefore, the initial administration of [ 18 F]fluciclovine to patients with brain or prostate cancer during PET procedures [2,3] is unlikely to cause drug transporter-mediated drug–drug interactions if generally accepted initial dosages for PET imaging are used.…”

Section: Discussionmentioning

confidence: 99%

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Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro

Ono

Baden

Okudaira

et al. 2016

IJMS

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[18F]Fluciclovine (trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid; anti-[18F]FACBC), a positron emission tomography tracer used for the diagnosis of recurrent prostate cancer, is transported via amino acid transporters (AATs) with high affinity (Km: 97–230 μM). However, the mechanism underlying urinary excretion is unknown. In this study, we investigated the involvement of AATs and drug transporters in renal [18F]fluciclovine reuptake. [14C]Fluciclovine (trans-1-amino-3-fluoro[1-14C]cyclobutanecarboxylic acid) was used because of its long half-life. The involvement of AATs in [14C]fluciclovine transport was measured by apical-to-basal transport using an LLC-PK1 monolayer as model for renal proximal tubules. The contribution of drug transporters herein was assessed using vesicles/cells expressing the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 4 (MRP4), organic anion transporter 1 (OAT1), organic anion transporter 3 (OAT3) , organic cation transporter 2 (OCT2), organic anion transporting polypeptide 1B1 (OATP1B1), and organic anion transporting polypeptide 1B3 (OATP1B3). The apical-to-basal transport of [14C]fluciclovine was attenuated by l-threonine, the substrate for system alanine-serine-cysteine (ASC) AATs. [14C]Fluciclovine uptake by drug transporter-expressing vesicles/cells was not significantly different from that of control vesicles/cells. Fluciclovine inhibited P-gp, MRP4, OAT1, OCT2, and OATP1B1 (IC50 > 2.95 mM). Therefore, system ASC AATs may be partly involved in the renal reuptake of [18F]fluciclovine. Further, given that [18F]fluciclovine is recognized as an inhibitor with millimolar affinity for the tested drug transporters, slow urinary excretion of [18F]fluciclovine may be mediated by system ASC AATs, but not by drug transporters.

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Section: Discussionmentioning

confidence: 99%

“…Recently, phase II clinical trials of [ 18 F]fluciclovine have been simultaneously conducted in Japan for the diagnosis of glioma [2] and primary prostate cancer [3]. …”

Section: Introductionmentioning

confidence: 99%

Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro

Ono

Baden

Okudaira

et al. 2016

IJMS

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“…The value of new amino acid PET tracers, such as α-11 C-methyl-tryptophan and 18 F-Fluciclovine as well as glutamine-based amino acid PET tracers has been evaluated with promising results in glioma patients in terms of tumor delineation, prognostication, and the differentiation of tumor recurrence from radiation injury (31,(118)(119)(120)(121)(122). Another interesting new PET target is the translocator protein (TSPO), a mitochondrial membrane protein highly expressed in activated microglia, macrophages, and neoplastic cells.…”

Section: Novel Pet Tracersmentioning

confidence: 99%

PET for Therapy Response Assessment in Glioblastoma

et al. 2017

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Glioblastoma (GB) is the most malignant and the most common type of glioma in adults, accounting for 60-70% of all malignant gliomas. Despite the current therapy, the clinical course of GB is usually rapid, with a mean survival time of approximately 1 year. For therapy response assessment in GB, magnetic resonance imaging (MRI) is the method of choice. In 2010, the Response Assessment in Neuro-Oncology (RANO) was introduced, including the tumor size (in 2D) as measured on T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR)-weighted images, in addition to the contrast-enhancing tumor part. Although the RANO criteria addressed some of the limitations of the previous MacDonald criteria for therapy evaluation in high-grade glioma, treatment-related side effects hamper correct response assessment. To address the above-mentioned drawbacks in the follow-up of GB, incorporating changes in tumor biology measured by advanced MRI and positron emission tomography (PET) imaging, which may precede anatomical changes of the tumor volume, is promising. Imaging biomarkers capable of predicting response at an early time point after treatment initiation are the premise of personalized treatment enabling change or GB Treatment Response Using PET 176 discontinuation of therapy to prevent ineffective treatment or adverse events of treatment. In this chapter, an overview of applicable PET tracers for the therapy response assessment in GB and the determination of tumor recurrence versus treatment-related effects is given.

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“…The study by Kondo et al form Japan assessed the efficacy and safety of 18 F-fluciclovine (aka. anti - 18 F-FACBC) in a phase IIa imaging trial of 5 patients with glioma (20). The United States Food and Drug Administration (FDA) approved 18 F-fluciclovine (commercialized as Axumin by Blue Earth Diagnostics, Inc., Oxford, UK) on May 27, 2016, for PET imaging evaluation of men with suspected prostate cancer recurrence based on elevated prostate specific antigen (PSA) levels following prior definitive treatment (21).…”

Section: Oncologymentioning

confidence: 99%

Highlights of articles published in annals of nuclear medicine 2016

Jadvar

2017

Eur J Nucl Med Mol Imaging

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This article is the first installment of highlights of selected articles published during 2016 in the Annals of Nuclear Medicine, an official peer-reviewed journal of the Japanese Society of Nuclear Medicine. A companion article highlighting selected articles published during 2016 in the European Journal of Nuclear Medicine and Molecular Imaging, which is the official peer-reviewed journal of the European Association of Nuclear Medicine, will also appear in the Annals Nuclear Medicine. This new initiative by the respective journals will continue as an annual endeavor and is anticipated to not only enhance the scientific collaboration between Europe and Japan but also facilitate global partnership in the field of nuclear medicine and molecular imaging.

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Phase IIa clinical study of [18F]fluciclovine: efficacy and safety of a new PET tracer for brain tumors

Cited by 70 publications

References 32 publications

Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro

Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro

PET for Therapy Response Assessment in Glioblastoma

Highlights of articles published in annals of nuclear medicine 2016

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