Autoradiography of Intracerebral Tumours in the Chick Embryo Model: A Feasibility Study Using Different PET Tracers.

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2025-01-21 DOI:10.1007/s11307-025-01983-9

Sandra Krause, Alexandru Florea, Chang-Hoon Choi, Wieland A Worthoff, Alexander Heinzel, Saskia Fischer, Nicole Burda, Bernd Neumaier, N Jon Shah, Philipp Lohmann, Felix M Mottaghy, Karl-Josef Langen, Carina Stegmayr

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Abstract

Purpose: In addition to rodent models, the chick embryo model has gained attention for radiotracer evaluation. Previous studies have investigated tumours on the chorioallantoic membrane (CAM), but its value for radiotracer imaging of intracerebral tumours has yet to be demonstrated.

Procedures: Human U87 glioblastoma cells and U87-IDH1 mutant glioma cells were implanted into the brains of chick embryos at developmental day 5. After 12-14 days of tumour growth, blood-brain-barrier integrity was evaluated in vivo using MRI contrast enhancement or ex vivo with Evans blue dye. The tracers O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET) (n = 5), 3,4-dihydroxy-6-[¹⁸F]-fluoro-L-phenylalanine ([¹⁸F]FDOPA) (n = 3), or [⁶⁸Ga] labelled quinoline-based small molecule fibroblast activation protein inhibitor ([⁶⁸Ga]FAPI-46) (n = 4) were injected intravenously if solid tumours were detected with MRI. For time-activity curves for [¹⁸F]FET, additional micro PET (µPET) was performed. The chick embryos were sacrificed 60 min post-injection, and cryosections of the tumour-bearing brains were produced and evaluated with autoradiography and immunohistochemistry.

Results: Intracerebral tumours were produced with a 100% success rate in viable chick embryos at the experimental endpoint. However, 52% of chick embryos (n = 85) did not survive the procedure to embryonic development day 20. For the evaluated radiotracers, the tumour-to-brain ratios (TBR) derived from ex vivo autoradiography, as well as the tracer kinetics derived from µPET for intracerebral chick embryo tumours, were comparable to those previously reported in rodents and patients: the TBRmean for [¹⁸F]FET was 1.69 ± 0.54 (n = 5), and 3.8 for one hypermetabolic tumour and < 2.0 for two isometabolic tumors using [¹⁸F]FDOPA, with a TBRmean of 1.92 ± 1,11 (n = 3). The TBRmean of [⁶⁸Ga]FAPI-46 for intracerebral chick embryo tumours was 19.13 ± 0.64 (n = 4). An intact blood-tumour barrier was observed in one U87-MG tumour (n = 5).

Conclusions: Radiotracer imaging of intracerebral tumours in the chick embryo offers a fast model for the evaluation of radiotracer uptake, accumulation, and kinetics. Our results indicate a high comparability between intracerebral tumour imaging in chick embryos and xenograft rodent models or brain tumour patients.

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不同PET示踪剂对鸡胚胎模型脑肿瘤的放射自显影研究。

目的：除啮齿类动物模型外，鸡胚模型在放射性示踪剂评价方面也备受关注。以前的研究已经研究了绒毛膜尿囊膜（CAM）上的肿瘤，但其对颅内肿瘤的放射性示踪成像价值尚未得到证实。方法：在发育第5天将人U87胶质瘤细胞和U87- idh1突变胶质瘤细胞植入鸡胚的大脑。肿瘤生长12-14天后，在体内用MRI增强或体外用Evans蓝染料评估血脑屏障的完整性。如果MRI检测到实体瘤，则静脉注射示踪剂O-（2-[18F]氟乙基）- l -酪氨酸（[18F]FET）（n = 5）、3,4-二羟基-6-[18F]-氟- l -苯丙氨酸（[18F]FDOPA）（n = 3）或[68Ga]标记的喹啉类小分子成纤维细胞激活蛋白抑制剂（[68Ga]FAPI-46）（n = 4）。对于[18F]场效应管的时间-活度曲线，进行额外的微PET（µPET）。注射后60分钟处死鸡胚，制作荷瘤脑冷冻切片，用放射自显影和免疫组织化学评价。结果：在实验终点，在活鸡胚胎中产生脑肿瘤的成功率为100%。然而，52%的鸡胚（n = 85）不能存活到胚胎发育第20天。对于评估的放射性示踪剂，由离体放射自显像获得的肿瘤脑比（TBR），以及由微PET获得的脑内鸡胚胎肿瘤示踪剂动力学，与先前在鼠类和患者中的报道相当：[18F]FET的TBR平均值为1.69±0.54 (n = 5)，一个高代谢肿瘤和18F]FDOPA的TBR平均值为3.8，TBR平均值为1.92±1,11 （n = 3）。[68Ga]FAPI-46对鸡脑内胚胎肿瘤的TBRmean为19.13±0.64 （n = 4）。在1例U87-MG肿瘤中观察到完整的血肿瘤屏障（n = 5）。结论：鸡胚脑肿瘤的放射性示踪成像为评估放射性示踪剂的摄取、积累和动力学提供了一个快速模型。我们的结果表明，鸡胚胎的脑肿瘤成像与异种移植的啮齿动物模型或脑肿瘤患者之间具有高度的可比性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.