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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

The acceleration of glucose accumulation in renal cell carcinoma assessed by FDG PET/CT demonstrated acquisition of resistance to tyrosine kinase inhibitor therapy

Authors: Noboru Nakaigawa, Keiichi Kondo, Daiki Ueno, Kazuhiro Namura, Kazuhide Makiyama, Kazuki Kobayashi, Koichi Shioi, Ichiro Ikeda, Takeshi Kishida, Tomohiro Kaneta, Ryogo Minamimoto, Ukihide Tateishi, Tomio Inoue, Masahiro Yao

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Tyrosine-kinase inhibitor (TKI) targeting angiogenesis improves the prognosis of patients with metastatic renal cell carcinoma (RCC), but its effect is temporary. In order to understand the mechanism by which RCC acquires resistance to TKI, we investigated the change of glucose accumulation in RCC by FDG PET/CT when they demonstrated progression disease (PD) against TKI.

Methods

We monitored the FDG accumulation in RCC of 38 patients treated with TKI by 162 PET/CT sequentially until they were judged to demonstrate PD. Standardized uptake value (SUV), a simplified index of tissue FDG accumulation rate, was measured, and the sequential changes of max SUVmax (the highest SUV in an individual patient) was analyzed. Additionally, the expression of glucose transporter 1 (GLUT-1) and associated proteins in 786-O cells cultured under hypoxia were analyzed.

Results

The 10 patients with RCC which FDG accumulation was accelerated after beginning of TKI treatment demonstrated PD soon. The other 28 patients with RCC which FDG accumulation was suppressed by TKI showed longer progression-free survival (3.6 months vs 6.5 months, P = 0.0026), but this suppression in most cases (96%) was temporary and FDG accumulation was accelerated when tumor demonstrated PD. Interestingly, the FDG accumulation at PD was higher than that before TKI treatment in the half cases. The acceleration of FDG accumulation was suppressed by following treatment by mammalian target of rapamycin (mTOR) inhibitor. Additionally, in vitro assay demonstrated that the expression of GLUT-1 was increased in the RCC cells surviving under hypoxia condition via mTOR pathway.

Conclusions

The acceleration of glucose accumulation dependent on mTOR in RCC assessed by FDG PET/CT demonstrated acquisition of resistance to TKI. FDG PET/CT had potential as an assessment method monitoring not only the initial response but also following status of RCC during TKI treatment.

Trial registration

UMIN0000008141, 11 Jun 2012. This trial was retrospectively registered.
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Metadata
Title
The acceleration of glucose accumulation in renal cell carcinoma assessed by FDG PET/CT demonstrated acquisition of resistance to tyrosine kinase inhibitor therapy
Authors
Noboru Nakaigawa
Keiichi Kondo
Daiki Ueno
Kazuhiro Namura
Kazuhide Makiyama
Kazuki Kobayashi
Koichi Shioi
Ichiro Ikeda
Takeshi Kishida
Tomohiro Kaneta
Ryogo Minamimoto
Ukihide Tateishi
Tomio Inoue
Masahiro Yao
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-3044-0

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