Skip to main content
Top
Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Research

Radiation treatment monitoring using multimodal functional imaging: PET/CT (18F-Fluoromisonidazole & 18F-Fluorocholine) and DCE-US

Authors: Natalia Arteaga-Marrero, Cecilie Brekke Rygh, Jose F. Mainou-Gomez, Tom C. H. Adamsen, Nataliya Lutay, Rolf K. Reed, Dag R. Olsen

Published in: Journal of Translational Medicine | Issue 1/2015

Login to get access

Abstract

Background

This study aims to assess the effect of radiation treatment on the tumour vasculature and its downstream effects on hypoxia and choline metabolism using a multimodal approach in the murine prostate tumour model CWR22. Functional parameters derived from Positron Emission Tomography (PET)/Computer Tomography (CT) with 18F-Fluoromisonidazole (18F-FMISO) and 18F-Fluorocholine (18F-FCH) as well as Dynamic Contrast-Enhanced Ultrasound (DCE-US) were employed to determine the relationship between metabolic parameters and microvascular parameters that reflect the tumour microenvironment. Immunohistochemical analysis was employed for validation.

Methods

PET/CT and DCE-US were acquired pre- and post-treatment, at day 0 and day 3, respectively. At day 1, radiation treatment was delivered as a single fraction of 10 Gy. Two experimental groups were tested for treatment response with 18F-FMISO and 18F-FCH.

Results

The maximum Standardized Uptake Values (SUVmax) and the mean SUV (SUVmean) for the 18F-FMISO group were decreased after treatment, and the SUVmean of the tumour-to-muscle ratio was correlated to microvessel density (MVD) at day 3. The kurtosis of the amplitude of the contrast uptake A was significantly decreased for the control tumours in the 18F-FCH group. Furthermore, the eliminating rate constant of the contrast agent from the plasma k el derived from DCE-US was negatively correlated to the SUVmean of tumour-to-muscle ratio, necrosis and MVD.

Conclusions

The present study suggests that the multimodal approach using 18F-FMISO PET/CT and DCE-US seems reliable in the assessment of both microvasculature and necrosis as validated by histology. Thus, it has valuable diagnostic and prognostic potential for early non-invasive evaluation of radiotherapy.
Literature
1.
go back to reference Hara T, Bansal A, DeGrado TR. Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C]acetate and [18F]FDG in cultured prostate cancer cells. Nucl Med Biol. 2006;33(8):977–84.CrossRefPubMed Hara T, Bansal A, DeGrado TR. Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C]acetate and [18F]FDG in cultured prostate cancer cells. Nucl Med Biol. 2006;33(8):977–84.CrossRefPubMed
2.
3.
go back to reference Vali R, Loidl W, Pirich C, et al. Imaging of prostate cancer with PET/CT using 18F-Fluorocholine. Am J Med Mol Imaging. 2015;5(2):96–108. Vali R, Loidl W, Pirich C, et al. Imaging of prostate cancer with PET/CT using 18F-Fluorocholine. Am J Med Mol Imaging. 2015;5(2):96–108.
4.
go back to reference Jadvar H. Prostate cancer: PET with 18F-FDG, 18F- or 11C-Acetate and 18F- or 11C-Choline. J Nucl Med. 2015;52:81–9.CrossRef Jadvar H. Prostate cancer: PET with 18F-FDG, 18F- or 11C-Acetate and 18F- or 11C-Choline. J Nucl Med. 2015;52:81–9.CrossRef
5.
go back to reference Heijmen L, ter Voert EGW, Punt CJA, et al. Monitoring hypoxia and vasculature during bevacizumab treatment in a murine colorectal cancer model. Contrast Media Mol Imaging. 2014;9:237–45.CrossRefPubMed Heijmen L, ter Voert EGW, Punt CJA, et al. Monitoring hypoxia and vasculature during bevacizumab treatment in a murine colorectal cancer model. Contrast Media Mol Imaging. 2014;9:237–45.CrossRefPubMed
7.
go back to reference Bansal A, Shuyan W, Hara T, et al. Biodisposition and metabolism of [(18F)] fluorocholine in 9L glioma cells and 9L glioma-bearing fisher rats. Eur J Med Mol Imaging. 2008;35(6):1192–203.CrossRef Bansal A, Shuyan W, Hara T, et al. Biodisposition and metabolism of [(18F)] fluorocholine in 9L glioma cells and 9L glioma-bearing fisher rats. Eur J Med Mol Imaging. 2008;35(6):1192–203.CrossRef
8.
go back to reference Janardhan S, Srivani P, Sastry GN. Choline kinase: an important target for cancer. Curr Med Chem. 2006;13(10):1169–86.CrossRefPubMed Janardhan S, Srivani P, Sastry GN. Choline kinase: an important target for cancer. Curr Med Chem. 2006;13(10):1169–86.CrossRefPubMed
9.
go back to reference Rajendran JG, Krohn KA. F-18 Fluoromisonidazole for imaging tumour hypoxia: imaging the microenvironment for personalized cancer therapy. Semin Nucl Med. 2014;45:151–62.CrossRef Rajendran JG, Krohn KA. F-18 Fluoromisonidazole for imaging tumour hypoxia: imaging the microenvironment for personalized cancer therapy. Semin Nucl Med. 2014;45:151–62.CrossRef
10.
go back to reference Chang JH, Lim Joon D, Lee ST, et al. Diffusion-weighted MRI, 11C-choline PET and 18F-fluorodeoxyglucose PET for predicting the Gleason score in prostate carcinoma. Eur Radiol. 2014;24:715–22.CrossRefPubMed Chang JH, Lim Joon D, Lee ST, et al. Diffusion-weighted MRI, 11C-choline PET and 18F-fluorodeoxyglucose PET for predicting the Gleason score in prostate carcinoma. Eur Radiol. 2014;24:715–22.CrossRefPubMed
11.
go back to reference Xie W, Tan AE, Cheng C, et al. Occult prostate cancer detected with 18F-fluorocholine positron emission tomography/computed tomography. World J Nucl Med. 2014;13(3):205–8.PubMedCentralCrossRefPubMed Xie W, Tan AE, Cheng C, et al. Occult prostate cancer detected with 18F-fluorocholine positron emission tomography/computed tomography. World J Nucl Med. 2014;13(3):205–8.PubMedCentralCrossRefPubMed
12.
go back to reference Paparo F, Piccardo A, Bacigalupo L, et al. Value of bimodal 18F-choline-PET/MRI and trimodal 18F-choline-PET/MRI/TRUS for the assessment of prostate cancer recurrence after radiation therapy and radical prostatectomy. Abdom Imaging. 2015. doi:10.1007/s00261-014-0345-0. Paparo F, Piccardo A, Bacigalupo L, et al. Value of bimodal 18F-choline-PET/MRI and trimodal 18F-choline-PET/MRI/TRUS for the assessment of prostate cancer recurrence after radiation therapy and radical prostatectomy. Abdom Imaging. 2015. doi:10.​1007/​s00261-014-0345-0.
13.
go back to reference Røe K, Seierstad T, Kristian A, et al. Longitudinal magnetic resonance imaging based assessment of vascular changes and radiation response in androgen-sensitive prostate carcinoma xenografts under androgen-exposed and androgen-deprived conditions. Neoplasia. 2010;12:818–25.PubMedCentralCrossRefPubMed Røe K, Seierstad T, Kristian A, et al. Longitudinal magnetic resonance imaging based assessment of vascular changes and radiation response in androgen-sensitive prostate carcinoma xenografts under androgen-exposed and androgen-deprived conditions. Neoplasia. 2010;12:818–25.PubMedCentralCrossRefPubMed
14.
go back to reference Sun C, Sboros V, Butler MB, et al. In vitro acoustic characterization of three phospholipid ultrasound contrast agents from 12 to 43 Mhz. Ultrasound Med Biol. 2014;40(3):541–50.PubMedCentralCrossRefPubMed Sun C, Sboros V, Butler MB, et al. In vitro acoustic characterization of three phospholipid ultrasound contrast agents from 12 to 43 Mhz. Ultrasound Med Biol. 2014;40(3):541–50.PubMedCentralCrossRefPubMed
15.
go back to reference Arteaga-Marrero N, Brekke Rygh C, Mainou-Gomez JF, et al. Multimodal approach to assess tumour vasculature and potential treatment effect with DCE-US and DCE-MRI quantification in prostate tumour xenografts. Contrast Media Mol Imaging. 2015;10(6):428–37.CrossRefPubMed Arteaga-Marrero N, Brekke Rygh C, Mainou-Gomez JF, et al. Multimodal approach to assess tumour vasculature and potential treatment effect with DCE-US and DCE-MRI quantification in prostate tumour xenografts. Contrast Media Mol Imaging. 2015;10(6):428–37.CrossRefPubMed
16.
go back to reference Brix G, Semmler W, Port R, et al. Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging. J Comput Assist Tomogr. 1991;15:621–8.CrossRefPubMed Brix G, Semmler W, Port R, et al. Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging. J Comput Assist Tomogr. 1991;15:621–8.CrossRefPubMed
17.
go back to reference Ma HT, Griffith JF, Dk Yeung, et al. Modified Brix model analysis of bone perfusion in subjects of varying bone mineral density. J Magn Reson Imaging. 2010;31:1169–75.CrossRefPubMed Ma HT, Griffith JF, Dk Yeung, et al. Modified Brix model analysis of bone perfusion in subjects of varying bone mineral density. J Magn Reson Imaging. 2010;31:1169–75.CrossRefPubMed
19.
21.
go back to reference Fack F, Espedal H, Keunen O, et al. Bevacizumab treatment induces metabolic adaptation toward anaerobic metabolism in glioblastomas. Acta Neuropathol. 2015;129(1):115–31.PubMedCentralCrossRefPubMed Fack F, Espedal H, Keunen O, et al. Bevacizumab treatment induces metabolic adaptation toward anaerobic metabolism in glioblastomas. Acta Neuropathol. 2015;129(1):115–31.PubMedCentralCrossRefPubMed
22.
go back to reference Nimmagadda S, Glunde K, Pomper MG, et al. Pharmacodynamic markers for choline kinase down-regulation in breast cancer cells. Neoplasia. 2009;11(5):477–84.PubMedCentralCrossRefPubMed Nimmagadda S, Glunde K, Pomper MG, et al. Pharmacodynamic markers for choline kinase down-regulation in breast cancer cells. Neoplasia. 2009;11(5):477–84.PubMedCentralCrossRefPubMed
23.
go back to reference Kukul D, Reischl G, Raguin O, et al. Assessment of PET tracer uptake in hormone-independent and hormone-dependent xenograft prostate cancer mouse models. J Nucl Med. 2011;52(10):1654–63.CrossRef Kukul D, Reischl G, Raguin O, et al. Assessment of PET tracer uptake in hormone-independent and hormone-dependent xenograft prostate cancer mouse models. J Nucl Med. 2011;52(10):1654–63.CrossRef
25.
go back to reference Rajendran JG, Mankoff DA, O’Sullivan F, et al. Hypoxia and glucose metabolism in malignant tumours: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging. Clin Cancer Res. 2004;10(7):2245–52.CrossRefPubMed Rajendran JG, Mankoff DA, O’Sullivan F, et al. Hypoxia and glucose metabolism in malignant tumours: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging. Clin Cancer Res. 2004;10(7):2245–52.CrossRefPubMed
26.
go back to reference Røe K, Aleksandersen TB, Kristian A, et al. Preclinical dynamic 18F-FDG PET—tumour characterization and radiotherapy response assessment by kinetic compartment analysis. Acta Oncol. 2010;49:914–21.CrossRefPubMed Røe K, Aleksandersen TB, Kristian A, et al. Preclinical dynamic 18F-FDG PET—tumour characterization and radiotherapy response assessment by kinetic compartment analysis. Acta Oncol. 2010;49:914–21.CrossRefPubMed
27.
go back to reference Baker DG, Krochak RJ. The response of the microvascular system to radiation: a review. Cancer Invest. 1989;7(3):287–94.CrossRefPubMed Baker DG, Krochak RJ. The response of the microvascular system to radiation: a review. Cancer Invest. 1989;7(3):287–94.CrossRefPubMed
28.
go back to reference Kwee SA, Wei H, Sesterhenn I, et al. Localization of primary prostate cancer with dual-phase 18F-fluorocholine PET. J Nucl Med. 2006;47(2):262–9.PubMed Kwee SA, Wei H, Sesterhenn I, et al. Localization of primary prostate cancer with dual-phase 18F-fluorocholine PET. J Nucl Med. 2006;47(2):262–9.PubMed
29.
go back to reference Behesthi M, Imamovic L, Broinger G, et al. 18F choline PET/CT in the preoperative staging of prostate cancer in patients with intermediate or high risk of extracapsular disease: a prospective study of 130 patients. Radiology. 2010;254(3):925–33.CrossRef Behesthi M, Imamovic L, Broinger G, et al. 18F choline PET/CT in the preoperative staging of prostate cancer in patients with intermediate or high risk of extracapsular disease: a prospective study of 130 patients. Radiology. 2010;254(3):925–33.CrossRef
31.
go back to reference Jain RK. Normalization of tumour vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307(5706):58–62.CrossRefPubMed Jain RK. Normalization of tumour vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307(5706):58–62.CrossRefPubMed
Metadata
Title
Radiation treatment monitoring using multimodal functional imaging: PET/CT (18F-Fluoromisonidazole & 18F-Fluorocholine) and DCE-US
Authors
Natalia Arteaga-Marrero
Cecilie Brekke Rygh
Jose F. Mainou-Gomez
Tom C. H. Adamsen
Nataliya Lutay
Rolf K. Reed
Dag R. Olsen
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0708-5

Other articles of this Issue 1/2015

Journal of Translational Medicine 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.