Relationships between oxygen and glucose metabolism in human liver tumours: positron emission tomography using 15O and 18F-deoxyglucose

Fukuda, Kazunori; Taniguchi, Hiroki; Koh, Toshimori; Kunishima, Satoshi; Yamagishi, Hisakazu

doi:10.1097/01.mnm.0000126627.01919.1d

Cited by 22 publications

(19 citation statements)

References 22 publications

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“…To minimize the effect of this confounder, only metastases larger than 3 cm were analyzed and only central portions of the metastases were graphically included in the VOIs. Perfusion measurements using 15 O-PET in liver tumors, including liver metastases of colorectal cancer, have been reported previously for small patient numbers, and the values for TBF in the current study are in the same range (18).…”

Section: Discussionsupporting

confidence: 61%

¹⁵O-Water PET Study of the Effect of Imatinib, a Selective Platelet-Derived Growth Factor Receptor Inhibitor, Versus Anakinra, an IL-1R Antagonist, on Water-Perfusable Tissue Fraction in Colorectal Cancer Metastases

et al. 2015

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High interstitial fluid pressure (IFP) in colorectal cancer metastases may decrease the uptake and, thus, the effects of antitumor drugs. Imatinib, a selective inhibitor of platelet-derived growth factor receptors, and anakinra, an interleukin-1 receptor antagonist, respectively, increase drug uptake or decrease IFP in preclinical models of carcinoma. Drug-induced decrease in IFP in human metastases has not been objectively shown but should be reflected by an increase in water-perfusable tissue fraction (PTF) or tumor blood flow (TBF) using 15 O-water PET/CT and kinetic modeling. Hence, the aim of this study was to assess the effects of imatinib and anakinra on PTF and TBF in colorectal cancer metastases in patients. Methods: Nine patients with documented progressive disease despite all established therapy underwent 15 O-water PET/CT at baseline and at 2 d and 6-7 d after the start of oral administration of imatinib (400 mg/d). After a washout period of 1 wk, the protocol was repeated with anakinra (100 mg/d) subcutaneously. Six patients underwent a second baseline scan on the same day to assess reproducibility of PTF and TBF measurements. Volumes of interest were drawn over liver metastases and aorta. PTF and TBF were calculated using the standard single-tissue-compartment model. Results: Imatinib administration during 6-7 d increased PTF from 0.62 ± 0.12 to 0.69 ± 0.13, compared with baseline and day 2 (P 5 0.02, Wilcoxon test). No significant changes were found in TBF. PTF values were no longer significantly different from baseline 1 wk after the last imatinib dosage. Anakinra induced no significant change in PTF or TBF. The repeatability coefficients of PTF and TBF in liver lesions were 22% and 28%, respectively. Conclusion: Imatinib increases PTF of colorectal cancer metastases in patients and hence may increase the delivery of antitumor drugs. 15 O-water PET/CT and kinetic modeling provide insights into the microenvironment of human cancers.

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Section: Discussionsupporting

confidence: 61%

¹⁵O-Water PET Study of the Effect of Imatinib, a Selective Platelet-Derived Growth Factor Receptor Inhibitor, Versus Anakinra, an IL-1R Antagonist, on Water-Perfusable Tissue Fraction in Colorectal Cancer Metastases

et al. 2015

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“…This finding is consistent with a set of evidences. (a) The computed OEF (Section 5.1) is in agreement with several OEF values reported for other fully aerobic systems (Connolly et al, 1997;Kenneth et al, 1998;Fukuda et al, 2004;Kalliokoski et al, 2005). (b) The fact that cells in the Lieberkhu¨n crypts metabolize preferentially butyrate, which is dissimilated through a highly aerobic process such as the b-oxidation (Section 4).…”

Section: Article In Presssupporting

confidence: 79%

A computer model of oxygen dynamics in human colon mucosa: Implications in normal physiology and early tumor development

Guebel

Torres

2008

Journal of Theoretical Biology

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“…As a consequence, many tumors are characterized by a functional coupling of blood flow and metabolism as evidenced by parallel increases in blood flow and tumor glucose metabolism as reported for numerous tumors, including those of the breast (27,30) and lung (31). In contrast, some tumors appear to display considerable variance between perfusion and metabolism with evidence of an uncoupling of blood flow from metabolism in specific cases (32), as recently reported for some head and neck cancers (33) and certain liver and metastatic colon cancers (34). Hence, in these cases it is important to be able to monitor both blood flow and metabolism to aid in the assessment of the type of cancer, the staging, or the planning of treatment regimens before therapy.…”

Section: Clinical Utility Of Perfusion Images For Tumor Imagingmentioning

confidence: 78%

Tumor Blood Flow Measured by PET Dynamic Imaging of First-Pass ¹⁸F-FDG Uptake: A Comparison with ¹⁵O-Labeled Water-Measured Blood Flow

Mullani¹,

Herbst²,

O’Neil³

et al. 2008

J Nucl Med

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PET molecular imaging of 15 O-labeled water is the gold standard for measuring blood flow in humans. However, this requires an on-site cyclotron to produce the short-lived 15 O tracer, which is cost-prohibitive for most clinical PET centers. The purpose of this study was to determine if the early uptake of 18 F-FDG could be used to measure regional blood flow in tumors in the absence of 15 O-water. Methods: PET scans were obtained in patients being evaluated for tumor perfusion and glucose metabolism in a phase I dose-escalating protocol for endostatin, a novel antiangiogenic agent. A 2-min perfusion scan was performed with a bolus injection of 2,220 MBq (60 mCi) of 15 O-water, which was followed by a 370-MBq (10 mCi) dose of 18 F-FDG. Four sequential scans of 18 F-FDG uptake were acquired, consisting of an early 2-min uptake scan-or first-pass scan-and 3 sequential 15-min late 18 F-FDG uptake scans. Regions of interest (ROIs) were drawn on 2 or more tumor sites and on back muscle, as a control ROI, for each patient. Arterial blood concentration was derived from the PET scans by drawing an ROI over a large artery in the field of view. Blood flow was computed with a simple 1-compartment blood flow model using the first 2 min of data after injection. Results: Blood flow estimated from the early uptake of 18 F-FDG was linearly correlated with 15 O-measured blood flow, with an intercept of 0.01, a slope of 0.86, and an R 2 regression coefficient of 0.74 (r 5 0.86). The 18 F-FDG tumor extraction fraction relative to 15 O-water averaged 0.86. A preliminary case study of a patient with prostate cancer confirms the utility of the first-pass 18 F-FDG blood flow analysis in tumor diagnosis. Conclusion: These results suggest that the first-pass uptake of 18 F-FDG may provide an estimate of perfusion in a tumor within the limitations of incomplete extraction of 18 F-FDG compared with 15 O-water.

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Relationships between oxygen and glucose metabolism in human liver tumours: positron emission tomography using 15O and 18F-deoxyglucose

Abstract: O and FDG PET showed a significant negative correlation between MRO2 and SUV in human liver tumours. In addition, MRO2 depends on Ft rather than on OEF.

Cited by 22 publications

References 22 publications

¹⁵O-Water PET Study of the Effect of Imatinib, a Selective Platelet-Derived Growth Factor Receptor Inhibitor, Versus Anakinra, an IL-1R Antagonist, on Water-Perfusable Tissue Fraction in Colorectal Cancer Metastases

¹⁵O-Water PET Study of the Effect of Imatinib, a Selective Platelet-Derived Growth Factor Receptor Inhibitor, Versus Anakinra, an IL-1R Antagonist, on Water-Perfusable Tissue Fraction in Colorectal Cancer Metastases

A computer model of oxygen dynamics in human colon mucosa: Implications in normal physiology and early tumor development

Tumor Blood Flow Measured by PET Dynamic Imaging of First-Pass ¹⁸F-FDG Uptake: A Comparison with ¹⁵O-Labeled Water-Measured Blood Flow

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Relationships between oxygen and glucose metabolism in human liver tumours: positron emission tomography using 15O and 18F-deoxyglucose

Abstract: O and FDG PET showed a significant negative correlation between MRO2 and SUV in human liver tumours. In addition, MRO2 depends on Ft rather than on OEF.

Cited by 22 publications

References 22 publications

15O-Water PET Study of the Effect of Imatinib, a Selective Platelet-Derived Growth Factor Receptor Inhibitor, Versus Anakinra, an IL-1R Antagonist, on Water-Perfusable Tissue Fraction in Colorectal Cancer Metastases

15O-Water PET Study of the Effect of Imatinib, a Selective Platelet-Derived Growth Factor Receptor Inhibitor, Versus Anakinra, an IL-1R Antagonist, on Water-Perfusable Tissue Fraction in Colorectal Cancer Metastases

A computer model of oxygen dynamics in human colon mucosa: Implications in normal physiology and early tumor development

Tumor Blood Flow Measured by PET Dynamic Imaging of First-Pass 18F-FDG Uptake: A Comparison with 15O-Labeled Water-Measured Blood Flow

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¹⁵O-Water PET Study of the Effect of Imatinib, a Selective Platelet-Derived Growth Factor Receptor Inhibitor, Versus Anakinra, an IL-1R Antagonist, on Water-Perfusable Tissue Fraction in Colorectal Cancer Metastases

¹⁵O-Water PET Study of the Effect of Imatinib, a Selective Platelet-Derived Growth Factor Receptor Inhibitor, Versus Anakinra, an IL-1R Antagonist, on Water-Perfusable Tissue Fraction in Colorectal Cancer Metastases

Tumor Blood Flow Measured by PET Dynamic Imaging of First-Pass ¹⁸F-FDG Uptake: A Comparison with ¹⁵O-Labeled Water-Measured Blood Flow