In vivo PET/MRI Imaging of the Chorioallantoic Membrane

Winter, Gordon; Koch, Andrea; Löffler, Jessica; Jelezko, Fedor; Lindén, Mika; Li, Hao; Abaei, Alireza; Zuo, Zhi; Beer, Ambros J.; Rasche, Volker

doi:10.3389/fphy.2020.00151

Cited by 15 publications

(17 citation statements)

References 119 publications

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“…Although tumors have been already successfully established on the CAM [4,[20][21][22][23][24][25][26][27][28][29], and PET-imaging studies are available [10,24,25,[30][31][32][33][34][35], systematic analyses of their use to evaluate the biodistribution of radiopharmaceuticals and direct comparisons with the in vivo gold standard are still rare [10].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Quantification of Target-Specific Accumulation of [18F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI

Löffler

Hamp

Scheidhauer

et al. 2021

Cancers

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Assessment of biodistribution and specific tumor accumulation is essential for the development of new radiopharmaceuticals and requires animal experiments. The HET-CAM (hens-egg test—chorioallantoic membrane) model can be used in combination with the non-invasive imaging modalities PET and MRI for pre-selection during radiopharmaceutical development to reduce the number of animal experiments required. Critical to the acceptance of this model is the demonstration of the quantifiability and reproducibility of these data compared to the standard animal model. Tumor accumulation and biodistribution of the PSMA-specific radiotracer [18F]F-siPSMA-14 was analyzed in the chick embryo and in an immunodeficient mouse model. Evaluation was based on MRI and PET data in both models. γ-counter measurements and histopathological analyses complemented these data. PSMA-specific accumulation of [18F]F-siPSMA-14 was successfully demonstrated in the HET-CAM model, similar to the results obtained by mouse model studies. The combination of MR and PET imaging allowed precise quantification of peptide accumulation, initial assessment of biodistribution, and accurate determination of tumor volume. Thus, the use of the HET-CAM model is suitable for the pre-selection of new radiopharmaceuticals and potentially reduces animal testing in line with the 3Rs principles of animal welfare.

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Section: Introductionmentioning

confidence: 99%

Comparison of Quantification of Target-Specific Accumulation of [18F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI

Löffler

Hamp

Scheidhauer

et al. 2021

Cancers

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“…Notably, the use of radiolabeled compounds and contrast agents for PET and MRI, respectively, have led to the need for suitable models for biodistribution and target specificity studies (Figure 3). The emergence of the CAM and its utility for imaging studies have been extensively reviewed [97]. The CAM offers, in a relatively quick and cost-effective manner, a platform to perform initial evaluations of novel MRI contrast agents and radiolabeled PET tracers.…”

Section: Applications In Imaging and Detectionmentioning

confidence: 99%

“…In certain cases, technologies evaluated on CAM tumor models are specifically developed for tumor imaging. Thus, tumor growth and other features of the embryo are monitored and visualized, for instance using MRI [140,160], MRI/PET [97], and PET/CT [98] (Figure 3).…”

Section: Imaging Of the Tumor And Vascular Networkmentioning

confidence: 99%

Tumor grafted – chick chorioallantoic membrane as an alternative model for biological cancer research and conventional/nanomaterial-based theranostics evaluation

Mapanao

Pei

Sarogni

et al. 2021

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: Advancements in cancer management and treatment are associated with strong preclinical research data, in which reliable cancer models are demanded. Indeed, inconsistent preclinical findings and stringent regulations following the 3Rs principle of reduction, refinement, and replacement of conventional animal models currently pose challenges in the development and translation of efficient technologies. The chick embryo chorioallantoic membrane (CAM) is a system for the evaluation of treatment effects on the vasculature, therefore suitable for studies on angiogenesis. Apart from vascular effects, the model is now increasingly employed as a preclinical cancer model following tumorgrafting procedures. Areas covered: The broad application of CAM tumor model is highlighted along with the methods for analyzing the neoplasm and vascular system. The presented and cited investigations focus on cancer biology and treatment, encompassing both conventional and emerging nanomaterial-based modalities. Expert opinion: The CAM tumor model finds increased significance given the influences of angiogenesis and the tumor microenvironment in cancer behavior, then providing a qualified miniature system for oncological research. Ultimately, the establishment and increased employment of such a model may resolve some of the limitations present in the standard preclinical tumor models, thereby redefining the preclinical research workflow.

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“…Based on own previous studies and data from other groups, the model appears suitable for efficient initial in vivo screening of the biodistribution of novel radiolabeled compounds prior to the evaluation in small animals [ 7 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. However, testing for target specificity of a radiolabeled tracer by blocking studies has not yet been demonstrated in the CAM model.…”

Section: Introductionmentioning

confidence: 99%

Blocking Studies to Evaluate Receptor-Specific Radioligand Binding in the CAM Model by PET and MR Imaging

Löffler

Herrmann

Scheidhauer

et al. 2022

Cancers

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Inhibition studies in small animals are the standard for evaluating the specificity of newly developed drugs, including radiopharmaceuticals. Recently, it has been reported that the tumor accumulation of radiotracers can be assessed in the chorioallantoic membrane (CAM) model with similar results to experiments in mice, such contributing to the 3Rs principles (reduction, replacement, and refinement). However, inhibition studies to prove receptor-specific binding have not yet been performed in the CAM model. Thus, in the present work, we analyzed the feasibility of inhibition studies in ovo by PET and MRI using the PSMA-specific ligand [18F]siPSMA-14 and the corresponding inhibitor 2-PMPA. A dose-dependent blockade of [18F]siPSMA-14 uptake was successfully demonstrated by pre-dosing with different inhibitor concentrations. Based on these data, we conclude that the CAM model is suitable for performing inhibition studies to detect receptor-specific binding. While in the later stages of development of novel radiopharmaceuticals, testing in rodents will still be necessary for biodistribution analysis, the CAM model is a promising alternative to mouse experiments in the early phases of compound evaluation. Thus, using the CAM model and PET and MR imaging for early pre-selection of promising radiolabeled compounds could significantly reduce the number of animal experiments.

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In vivo PET/MRI Imaging of the Chorioallantoic Membrane

Cited by 15 publications

References 119 publications

Comparison of Quantification of Target-Specific Accumulation of [18F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI

Comparison of Quantification of Target-Specific Accumulation of [18F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI

Tumor grafted – chick chorioallantoic membrane as an alternative model for biological cancer research and conventional/nanomaterial-based theranostics evaluation

Blocking Studies to Evaluate Receptor-Specific Radioligand Binding in the CAM Model by PET and MR Imaging

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