Cyp4v3(-/-) mice represent a promising preclinical model that may be used to better understand the disease etiology and to evaluate pharmacotherapies for this devastating condition.
The purpose of this study was to measure the errors introduced by regular calibration of PET/CT scanners and to minimize the effect of calibration error on standardized uptake value measurements.
Methods
Global calibration factors from 2 PET/CT scanners were recorded for 3.5 and 1.8 y, comparing manufacturer-recommended protocols with modified protocols to evaluate error contributions due to operator-influenced procedures. Dose calibrator measurements were evaluated using National Institute of Standards and Technology–traceable sources.
Results
Dose calibrator variability was less than 1%, although there was a consistent bias. Global scaling variability was reduced from 6% to 4% for scanner 1 and from 11% to 4% for scanner 2 when quality assurance and quality control procedures were applied to the calibration protocol. When calibrations were done using a 68Ge/68Ga phantom, the variability for both scanners was reduced to approximately 3%.
Conclusion
Applying quality assurance and quality control procedures to scanner calibration reduces variability, but there is a still a residual longitudinal scanner variability of 3%–4%. The procedures proposed here reduce the impact of operator error on scanner calibration and thereby minimize longitudinal variability in standarized uptake value measurements.
Drug metabolism and transport processes in the liver, intestine and kidney that affect the pharmacokinetics and pharmacodynamics of therapeutic agents have been studied extensively. In contrast, comparatively little research has been conducted on these topics as they pertain to the eye. Recently, however, catalytic functions of ocular cytochrome P450 enzymes have gained increasing attention, in large part due to the roles of CYP1B1 and CYP4V2 variants in primary congenital glaucoma and Bietti’s corneoretinal crystalline dystrophy, respectively. In this review, we discuss challenges to ophthalmic drug delivery, including Phase I drug metabolism and transport in the eye, and the role of three specific P450s, CYP4B1, CYP1B1 and CYP4V2 in ocular inflammation and genetically determined ocular disease.
This is the first report of a homozygous R400C mutation in CYP4V2 with protein modelling showing high likelihood of enzyme dysfunction. The comprehensive long-term clinical follow-up provides insight into disease progression and highlights possible anti-inflammatory modulation of disease severity.
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