Autoradiography of intracerebral tumours in the chick embryo model : a feasibility study using different PET tracers

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.