Detection of metastatic bone lesions in breast cancer patients: Fused 18F-Fluoride-PET/MDCT has higher accuracy than MDCT. Preliminary experience

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Abstract

Purpose

So far, no studies comparing 18F-Fluoride-PET/CT and MDCT for the detection of bone metastases are available. We compared the accuracy of 18F-Fluoride-PET/CT (MDCT: 3.75 mm thickness-image-reconstruction), whole-body Multi-Detector-CT (MDCT: 1.25 mm thickness-image-reconstruction) and 18F-Fluoride-PET/MDCT (MDCT: 1.25 mm thickness-image-reconstruction) in identifying bone metastases in breast cancer patients.

Methods

We studied 39 breast cancer patients for bone metastases. Imaging was performed on an integrated PET/MDCT-system; CT images were reconstructed at 3.75 mm and 1.25 mm thickness. Two nuclear medicine physicians and one radiologist interpreted blindly 18F-Fluoride-PET/CT, 18F-Fluoride-PET/MDCT and MDCT. MDCT at 12 months served as the standard of reference.

Results

Overall, 662 bone lesions were detected in our analysis. Of these, 542 were malignant and 120 were benign according to the standard of reference. 18F-Fluoride-PET/CT detected 491 bone metastases, 114 (23%) of which displayed no clear morphological changes on MDCT, whereas MDCT detected 416 bone metastases, 39 (9.3%) of which showed no 18F-Fluoride-PET uptake. Overall sensitivity and specificity were: 91% and 91%, respectively, for 18F-Fluoride-PET/CT, and 77% and 93% for MDCT. The integrated assessment of 18F-Fluoride-PET/MDCT yielded sensitivity and specificity values of 98% and 93%, respectively.

Conclusions

18F-Fluoride-PET/MDCT has higher diagnostic accuracy than 18F-Fluoride-PET/CT and MDCT for the evaluation of bone metastases in breast cancer.

Introduction

Planar bone scintigraphy (BS) can detect bone metastases several months before plain radiography [1]. Some comparative studies have shown that MRI can reveal significantly more metastases in the spine than conventional BS [2], [3]. However, whole-body MRI has some inherent limitations (including long examination time, limited access to high-field-strength machines and high cost). By contrast, multi-detector computed tomography (MDCT) is widely available in routine clinical practice and is increasingly utilized in the staging of primary malignant diseases, since its small-thickness (1.25 mm or less) image reconstruction yields high-quality multiplanar reconstructions for the assessment of the entire skeletal system [4]. MDCT is often used when BS findings are doubtful and are not corroborated radiographically. Moreover, MDCT can assess the type of skeletal metastases, distinguishing among osteolytic, osteoblastic and mixed bone lesions [4]. Today BS and MDCT are considered the “first-step” techniques for whole-skeleton investigations [5].

18F-Fluoride is a PET tracer, and is a sensitive marker of increased regional blood flow and osteoblastic metabolism. It displays high blood clearance (nearly 100%), approximately 70% greater than the conventional 99mTc-methylenediphosphonate (MDP) used for BS [6]. However, increased 18F-Fluoride uptake is not specific for tumoral bone involvement, and the high sensitivity of 18F-Fluoride-PET may also be associated with a higher detection rate of benign bone lesions [6].

18F-Fluoride-PET has been shown to be more accurate than BS in detecting both sclerotic and lytic lesions in various malignancies and to be a valid alternative to BS in patients at high risk of metastatic bone disease [7]. So far, however, no data comparing 18F-Fluoride-PET and MDCT are available.

Some recent studies have indicated that PET/CT in which 18F-FDG is used as the tumour-imaging agent displays greater diagnostic accuracy than PET alone in tumour detection [8], [9]. In this setting, the application of 18F-Fluoride PET/CT with an optimised CT protocol, namely the small-thickness image reconstruction allowed by MDCT, may provide additional information and help to interpret Fluoride uptake correlated with bone density abnormalities detected by MDCT.

The aim of our study was to prospectively compare the overall diagnostic accuracy of 18F-Fluoride PET/CT, using 3.75 mm thickness MDCT reconstructed axial images that are mainly used in every day nuclear medicine clinical practice, with 1.25 mm thickness MDCT images (that allow Multi Planar Reconstruction-MPR) and 18F-Fluoride PET/MDCT (1.25 mm thickness MDCT images). We performed lesion-based and patient-based analyses. The study was carried out in patients with advanced breast cancer, since the skeleton is the most common site of distant metastases, and breast cancer can result in either osteolytic or osteoblastic metastasis; it therefore enabled the different imaging modalities to be extensively evaluated in different types of bone lesions.

Section snippets

Patients and methods

This study involved 39 women with histologically proven advanced breast cancer referred for skeletal surveys; patients had bone pain and/or increased tumour markers and/or evidence of bone metastases on previous thoraco-abdominal MDCT. The Local Ethics Committee approved the study, and informed consent was obtained for all patients. The main patient and tumour characteristics are summarised in Table 1.

Both PET and MDCT images were acquired on an integrated 16-detector-row PET/MDCT system

Lesion-based analysis

Overall, 662 bone lesions were detected in our analysis. Of these, 542 were malignant and 120 were benign according to the standard of reference (Table 2).

18F-Fluoride-PET/CT detected 491 sites of bone uptake classified as bone metastases, 114 (23%) of which displayed no clear morphological change on MDCT. A case is illustrated in Fig. 1. Eleven bone lesions positive on 18F-Fluoride-PET/CT were classified as false-positive one year later.

MDCT detected 416 bone metastases, 39 of which were

Discussion

The favourable pharmacokinetic characteristics of 18F-Fluoride has led to an increasing use of 18F-Fluoride-PET in the evaluation of bone metastases [10]. Lesions detected on 18F-Fluoride PET often require correlation with CT or MRI for further validation. Recent data have demonstrated that 18F-Fluoride PET/CT is a highly sensitive imaging modality for the evaluation of bone metastases in prostate cancer [11], [12]. In the present study we prospectively compared 18F-Fluoride-PET/CT, MDCT and 18

Conclusions

Our data showed relatively high agreement (71% of lesions and 100% of patients) between 18F-Fluoride-PET/CT and MDCT in detecting bone metastases in breast cancer patients. However, 18F-Fluoride-PET/CT was more sensitive than MDCT in detecting bone involvement, and integrated reading of the two different modalities (18F-Fluoride-PET/MDCT) yielded the best diagnostic interpretation of bone involvement. Further confirmation on a larger group of patients over a longer period of follow-up may

Conflict of interest

The authors declare no conflict of interest.

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