| 51. |
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| 52. |
- Linnman, Clas, et al.
(author)
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Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
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Journal article (peer-reviewed)abstract
- Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.
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| 55. |
- Lubberink, Mark, et al.
(author)
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O-15-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
- 2015
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 56:8, s. 1144-1149
-
Journal article (peer-reviewed)abstract
- 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 O-15-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 O-15-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 = 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. O-15-water PET/CT and kinetic modeling provide insights into the microenvironment of human cancers.
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| 56. |
- Lubberink, Mark, et al.
(author)
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The water-perfusable tissue fraction of colorectal cancer metastases is increased by the selective PDGF-receptor inhibitor imatinib but not the IL-1 receptor antagonist anakinra, a study using serial dynamic 15O-water PET.
- 2015
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 56:8, s. 1144-1149
-
Journal article (peer-reviewed)abstract
- High interstitial fluid pressure (IFP) in colorectal cancer metastases may decrease the uptake and, thus, the effects of anti-tumor drugs. Imatinib, a selective inhibitor of PDGF receptors, and anakinra, an interleukin-1 receptor antagonist, respectively, increase drug uptake and/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 modelling. 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.
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