Preclinical evaluation of [18F]cabozantinib as a PET imaging agent in a prostate cancer mouse model

Lien, Vegard Torp; Celen, Sofie; Nuruddin, Syed; Attili, Bala; Doumont, Gilles; Simaeys, Gaëtan Van; Bormans, Guy; Klaveness, Jo; Olberg, Dag Erlend

doi:10.1016/j.nucmedbio.2020.12.002

Cited by 3 publications

(5 citation statements)

References 40 publications

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“…Cabozantinib and tinvantinib, both obtained from Selleckchem (via Absource Diagnostics GmbH, Munich, Germany), were used for pharmacological inhibition. Cabozantinib, a receptor tyrosine kinase inhibitor (TKI) that targets multiple tyrosine kinases including VEGFR2, RET, AXL, FLT3, c-KIT, and c-MET, is clinically approved for the treatment of medullary thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma [ 21 ]. Tivantinib, a selective inhibitor of unactivated c-MET and its self-phosphorylation, has been successful in phase II trials; however, it failed in two phase III trials for second-line treatment of advanced high-Met hepatocellular carcinoma [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer

Thomas¹,

Slade²,

Blaheta³

et al. 2022

Cancers

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Section: Methodsmentioning

confidence: 99%

Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer

Thomas¹,

Slade²,

Blaheta³

et al. 2022

Cancers

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“…Derivatives or isotopologues of imatinib [ 303 , 310 , 312 , 475 , 476 ], sorafenib [ 315 , 477 ], lapatinib [ 478 , 479 ], sunitinib [ 313 ], nintedanib [ 23 ], cabozantinib [ 480 ] and vandetanib [ 481 , 482 ] have been radiolabeled and further developed preclinically to various degrees, yet no translation into the clinical setting was achieved ( Table S1 ). Multi-kinase inhibitors are likely to be of limited use to elucidate the expression of one individual RTK.…”

Section: Multi-kinase Inhibition For Gb Therapymentioning

confidence: 99%

“…Another possible disadvantage of broad spectrum TKIs is that normal tissues might be targeted as well, resulting in additional, unwanted toxicity [ 23 ]. For example, [ 18 F]F-cabozantinib demonstrated a high non-specific binding in tumor and unfortunately in heart tissue as well [ 480 ]. [ 18 F]F-dasatinib (SKI249380) is currently under investigation in a clinical trial for potential diagnostic imaging in a wide range of solid tumors, but GB was excluded (NCT01916135) [ 67 ].…”

Section: Multi-kinase Inhibition For Gb Therapymentioning

confidence: 99%

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

et al. 2021

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Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up the scope for theranostic applications. In this review, the present status of RTKIs for the treatment, nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their potential to become new therapeutic GB radiopharmaceuticals.

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“…Several strategies to image MET expression in vivo have been explored, predominantly using peptides or monoclonal antibodies 13,14 . For radiotracers based on small molecular weight compounds targeting the intracellular domain of MET, there is only a few reports so far 15–17 . Because therapeutic PKIs bind intracellularly, radiotracers binding to the same active site may be beneficial to properly assess target expression and engagement.…”

Section: Introductionmentioning

confidence: 99%

“…13,14 For radiotracers based on small molecular weight compounds targeting the intracellular domain of MET, there is only a few reports so far. [15][16][17] Because therapeutic PKIs bind intracellularly, radiotracers binding to the same active site may be beneficial to properly assess target expression and engagement. In this study, we aimed to develop a synthesis of [ 18 F]2 and to evaluate its characteristics both in vitro and in vivo.…”

mentioning

confidence: 99%

Synthesis and preclinical evaluation of a selective MET kinase positron emission tomography tracer

Lien,

Hauge,

Nuruddin

et al. 2023

Labelled Comp Radiopharmac

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The tyrosine kinase MET (hepatocyte growth factor receptor) is activated or mutated in a wide range of cancers and is often correlated with a poor prognosis. Precision medicine with positron emission tomography (PET) can potentially aid in the assessment of tumor biochemistry and heterogeneity, which can prompt the selection of the most effective therapeutic regimes. The selective MET inhibitor PF04217903 (1) formed the basis for a bioisosteric replacement, leading to the deoxyfluorinated analog [18F]2. [18F]2 could be synthesized with a “hydrous fluoroethylation” protocol in 6.3 ± 2.6% radiochemical yield and a molar activity of >50 GBq/μmol. In vitro autoradiography indicated that [18F]2 selectively binds to MET in PC3 tumor tissue, and in vivo biodistribution in mice showed predominantly a hepatobiliary excretion along with a low retention of radiotracer in other organs.

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Preclinical evaluation of [18F]cabozantinib as a PET imaging agent in a prostate cancer mouse model

Cited by 3 publications

References 40 publications

Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer

Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

Synthesis and preclinical evaluation of a selective MET kinase positron emission tomography tracer

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