18F] Sodium Fluoride PET Kinetic Parameters in Bone Imaging.

Tanuj Puri,Michelle L Frost,Gary J Cook,Glen M Blake

doi:10.3390/tomography7040071

Tanuj Puri, Michelle L Frost + Show 2 more

Open Access

https://doi.org/10.3390/tomography7040071

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Abstract

This report describes the significance of the kinetic parameters (k-values) obtained from the analysis of dynamic positron emission tomography (PET) scans using the Hawkins model describing the pharmacokinetics of sodium fluoride ([18F]NaF) to understand bone physiology. Dynamic [18F]NaF PET scans may be useful as an imaging biomarker in early phase clinical trials of novel drugs in development by permitting early detection of treatment-response signals that may help avoid late-stage attrition.

Highlights

The assessment of skeletal metabolism is important for understanding the pathophysiology and for measuring the response to treatment of metabolic bone diseases such as osteoporosis [1] and for investigating and differentiating the different effects of chronic kidney disease on bone [2]
Bone biopsy is considered the gold standard for measuring bone turnover; it is limited to a single biopsy site at the iliac crest, subject to large measurement errors and is invasive and uncomfortable for the patient [2,3,4,5,6,7,8] multiple biopsies are required to assess treatment response and disease progression
The most commonly used and practical method is the measurement of bone turnover markers in serum and urine, which can show a large and rapid response within weeks of the commencement of treatment for osteoporosis [9,10]

Summary

Introduction

The assessment of skeletal metabolism is important for understanding the pathophysiology and for measuring the response to treatment of metabolic bone diseases such as osteoporosis [1] and for investigating and differentiating the different effects of chronic kidney disease on bone [2]. In studies measuring response to treatment, anabolic treatments (such as teriparatide) tend to increase k3/(k2 + k3) [36] and antiresorptive treatments (such as risedronate) tend to decrease k3/(k2 + k3) [33], in turn affecting the fraction of tracer that underwent specific binding to bone mineral space (Figure 1). Considering that the ratio of the treatment response divided by the precision error was highest for k3/(k2 + k3) among all the Hawkins’s model parameters [43], and that this ratio represents the fraction of tracer that undergoes binding to the bone mineral and of treatment effect [33,34,37], the measurement of changes in k3/(k2 + k3) may be considered one of the most effective means (alongside the Ki parameter) of using [18F]NaF dynamic PET scans to noninvasively investigate changes in bone formation rate. The arterial plasma concentration of tracer is depressed and SUV measurements can give a false impression of true regional change [58]

Precision Errors in Measuring K-Parameters

Findings

10. Conclusions