[177Lu]pentixather: comprehensive preclinical evaluation of a first CXCR4-directed endoradiotherapeutic agent


Based on the clinical relevance of the chemokine receptor 4 (CXCR4) as a molecular target in cancer and on the success of [68Ga]pentixafor as an imaging probe for high-contrast visualization of CXCR4-expression, the spectrum of clinical CXCR4-targeting was expanded towards peptide receptor radionuclide therapy (PRRT) by the development of [177Lu]pentixather…

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Dendritic poly-chelator frameworks for multiple bioconjugation


Starting from multifuntional triazacyclononane-triphosphinate chelator cores, dendritic molecules with the ability to bind metal ions within their framework were synthesized. A cooperative interaction of the chelator cages resulted in a markedly increased affinity towards 67/68GaIII. A hexameric PSMA inhibitor conjugate with high affinity (IC50=1.2 nM) and favorable in-vivo PET imaging properties demonstrated practical applicability. The novel scaffolds are useful for synthesis of well-defined multimodal imaging probes or theranostics.

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[64Cu]NOTA-pentixather enables high resolution PET imaging of CXCR4 expression in a preclinical lymphoma model


The chemokine receptor 4 (CXCR4) is an important molecular target for both visualization and therapy of tumors. The aim of the present study was the synthesis and preclinical evaluation of a 64Cu-labeled, CXCR4-targeting peptide for positron emission tomography (PET) imaging of CXCR4 expression in vivo. For this purpose, 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), or 1,4,7-triazacyclononane-triacetic acid (NOTA) was conjugated to the highly affine…

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A Comprehensive Evaluation of the Activity and Selectivity Profile of Ligands for RGD-binding Integrins


Integrins, a diverse class of heterodimeric cell surface receptors, are key regulators of cell structure and behaviour, affecting cell morphology, proliferation, survival and differentiation. Consequently, mutations in specific integrins, or their deregulated expression, are associated with a variety of diseases.

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[68Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma – Comparison to [18F]FDG and laboratory values


Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [68Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies. Thirty-five patients with MM underwent [68Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [18F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity...

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Investigating the Chemokine Receptor 4 as Potential Theranostic Target in Adrenocortical Cancer Patients


Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor with limited treatment options. Preclinical studies confirmed overexpression of the chemokine receptor 4 (CXCR4) in this cancer type. This study aimed to analyze the role of CXCR4 imaging using Ga-pentixafor for ACC staging and selection of patients for CXCR4-directed endoradiotherapy. Thirty patients with histologically proven advanced, metastasized ACC underwent…

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