The water-perfusable tissue fraction of @entity14 metastases is increased by the selective PDGF-receptor inhibitor XXXX but not the IL-1 receptor antagonist anakinra, a study using serial dynamic 15O-water PET.

@entity1 @entity5 @entity409 @entity189 @entity14 @entity8493 @entity2213
UNASSIGNED: High interstitial fluid pressure (IFP) in @entity14 metastases may decrease the uptake and, thus, the effects of anti- @entity5 drugs. @entity2213 , 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 @entity189 . Drug-induced decrease in IFP in @entity1 metastases has not been objectively shown, but should be reflected by an increase in water-perfusable tissue fraction (PTF) or @entity5 ( @entity5 ) using [ @entity8493 ]water PET/CT and kinetic modelling. Hence, the aim of this study was to assess the effects of @entity2213 and anakinra on PTF and @entity5 in @entity14 metastases in @entity1 . METHODS: Nine @entity1 with documented progressive disease in spite of all established therapy underwent @entity8493 -water PET/CT at baseline, and at 2 days and 6-7 days after start of oral administration of 400 mg/day @entity2213 . After a washout period of one week the protocol was repeated with anakinra 100mg/day subcutaneously. Six @entity1 underwent a second baseline scan on the same day to assess reproducibility of PTF and @entity5 measurements. Volumes of interest (VOIs) were drawn over liver metastases and aorta. PTF and @entity5 were calculated using the standard single tissue compartment model. RESULTS: @entity2213 administration during 6-7 days increased PTF from 0.62    0.12 to 0.69    0.13 compared to baseline and day 2 (P = 0.02, Wilcoxon test). No significant changes were found in @entity5 . PTF values were no longer significantly different from baseline one week after last @entity2213 dosage. Anakinra induced no significant change in PTF or @entity5 . The repeatability coefficients of PTF and @entity5 in @entity409 were 22% and 28%, respectively. CONCLUSION: @entity2213 increases PTF of @entity14 metastases in @entity1 , and hence may increase delivery of anti- @entity5 drugs. @entity8493 -water PET/CT and kinetic modelling provides novel insights into the microenvironment of @entity1 @entity5 .
