First approved in 1962 for detection of osteogenic activity, 18F-NaF has been the subject of intensive research due to its ability to detect metastatic bone disease in PET/CT scans. This radiotracer of bone turnover has shown potential as an imaging biomarker for assessing response to treatment of bone metastases. 18F-NaF PET/CT is considered particularly promising for patients with metastatic prostate cancer because the majority of these patients develop clinically detectable osteoblastic bone metastases. The advantages of 18-F-NaF PET/CT compared to bone scintigraphy using 99Tc-MDP include higher skeletal uptake, faster blood clearance, higher sensitivity and higher specificity.

The importance of a multicentre study – such as this one, conducted at the University of Wisconsin Carbone Cancer Center, Memorial Sloan Kettering Cancer Center and the Center for Cancer Research of the National Cancer Institute – is that the results can be used to establish quantitative criteria for treatment response assessment.

Test/retest scans

The patient cohort included 35 patients with metastatic castrate-resistant prostate cancer and multiple bone metastases. Patients received two whole-body scans (test/retest) within a five-day period using two models of scanners. Scans were harmonized across imaging centres to obtain equivalent image quality and quantitative accuracy. Quantitative Total Bone Imaging (QTBI), developed in the University of Wisconsin-Madison's Image-Guided Therapy Lab, was used to semi-automatically segment bone lesions. The extensive level and quantitative accuracy of disease detection was enabled using QTBI.

A total of 411 bone lesions (a median of eight per patient) larger than 1.5 cm3 were identified, located across the skeleton, with the majority localized to the spine. Lead author Christie Lin, a PhD student in medical physics at the University of Wisconsin-Madison, and co-authors stated that this justified the use of measuring SUVs in individual lesions. Scanner harmonization enabled the incorporation of data across multiple imaging centres and cross-comparison of repeatability. However, the authors still observed significant difference in repeatability between different centres, most likely due to different degrees of conformation to the imaging protocol.

Test/retest 18F-NaF PET/CT imaging enabled the establishment of quantitative limits of agreement to define response to treatments of metastatic bone disease. These limits can now be used to assess whether response to therapy is significant or not, greatly increasing confidence in 18F-NaF PET/CT as a tool for clinical decision making as well as drug development. Further research involves assessment of 18F-NaF PET/CT as a potential prognostic and predictive biomarker of clinical response assessment, assessment of response heterogeneity in metastatic disease, and understanding of biological (genomic) differences leading to various levels of resistance to various therapies.

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