In:
EJNMMI Research, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-12)
Abstract:
[ 18 F]Fluoromisonidazole ([ 18 F]FMISO) is a PET imaging probe widely used for the detection of hypoxia. We previously reported that [ 18 F]FMISO is metabolized to the glutathione conjugate of the reduced form in hypoxic cells. In addition, we found that the [ 18 F]FMISO uptake level varied depending on the cellular glutathione conjugation and excretion ability such as enzyme activity of glutathione-S-transferase and expression levels of multidrug resistance-associated protein 1 (MRP1, an efflux transporter), in addition to the cellular hypoxic state. In this study, we evaluated whether MRP1 activity affected [ 18 F]FMISO PET imaging. Methods FaDu human pharyngeal squamous cell carcinoma cells were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, incubated with [ 18 F]FMISO for 4 h under hypoxia, and their radioactivity was then measured. FaDu tumor-bearing mice were intravenously injected with [ 18 F]FMISO, and PET/CT images were acquired at 4 h post-injection (1st PET scan). Two days later, the same mice were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, and PET/CT images were acquired (2nd PET scan). Results FaDu cells pretreated with MRP1 inhibitors exhibited significantly higher radioactivity than those without inhibitor treatment (cyclosporine A: 6.91 ± 0.27, lapatinib: 10.03 ± 0.47, MK-571: 10.15 ± 0.44%dose/mg protein, p 〈 0.01). In the in vivo PET study, the SUV mean ratio in tumors [calculated as after treatment (2nd PET scan)/before treatment of MRP1 inhibitors (1st PET scan)] of the mice treated with MRP1 inhibitors was significantly higher than those of control mice (cyclosporine A: 2.6 ± 0.7, lapatinib: 2.2 ± 0.7, MK-571: 2.2 ± 0.7, control: 1.2 ± 0.2, p 〈 0.05). Conclusion In this study, we revealed that MRP1 inhibitors increase [ 18 F]FMISO accumulation in hypoxic cells. This suggests that [ 18 F]FMISO-PET imaging is affected by MRP1 inhibitors independent of the hypoxic state.
Type of Medium:
Online Resource
ISSN:
2191-219X
DOI:
10.1186/s13550-021-00752-3
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2619892-7
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