In vivo PET imaging of 5T4 positive tumor cells using 89Zr-DFO-MY9

Introduction: Background: The 5T4 oncofoetal antigen is considered a valuable tumor-associated antigen, which is expressed in many different cancers, but is rarely expressed in normal adult tissues. And cell surface expression of 5T4 is an important property for antibody-targeted therapies. It has been shown that 5T4 is expressed on tumour-initiating cells (TICs) and associated with worse clinical outcome. Moreover, decreased adherence due to 5T4 expression may be associated with cancer spread.

Purpose: Herein, we generate and labeled the 5T4 targeting antibody fragments (MY9) with ⁸⁹Zr, and investigate whether positron-emission tomography (PET) were sensitive approaches for detecting and quantitating 5T4⁺ solid tumor in vivo.

Methods: MY9was labeled with ⁸⁹Zr (using DFO as bi-functional chelator). The quality control was analyzed by Radio-TLC. The invitro stability was evaluated in saline and 5%HSA. Micro-PET imaging studies were performed in BxPC3 and MDA-MB-231 tumor models. Both model mice were injected with 3.33 MBq of ⁸⁹Zr-DFO-MY9 via tail vein. Then 10 min static PET scans were acquired at each time point from 3 h to 144 h post injection (p.i.), respectively. Using a small-animal PET/CT scanner, the PET images were reconstructed by Avatar 3.

Results: ⁸⁹Zr-DFO-MY9 were successfully constructed with 80-90% yield over 99% radiochemical purity. The radiochemical purity of ⁸⁹Zr-DFO-MY9 at 120 h after labeling showed high in vitro stability. The tumor uptake of ⁸⁹Zr-DFO-MY9 in BxPC3 models could be clearly visualized at 15 h with SUVmax 2.69 ± 0.31 and remained to be clearly visible up to 144 h post-injection. The tumor uptake of ⁸⁹Zr-DFO-MY9 in MDA-MB-231 models could be clearly visualized at 24 h with SUVmax 1.65 ± 0.24 and remained to be clearly visible up to 96 h post-injection.

Conclusions: 5T4 is an attractive target for immune intervention in cancer. Targeted molecular imaging allows for real-time, noninvasive, and quantitative detection of 5T4⁺ TICs in vivo. It may be possible to early warning of early detection of tumor prognosis and recurrence.

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