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Measuring [18F]FDG uptake in breast cancer during chemotherapy: comparison of analytical methods

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Abstract

Over the years several analytical methods have been proposed for the measurement of glucose metabolism using fluorine-18 fluorodeoxyglucose ([18F]FDG) and positron emission tomography (PET). The purpose of this study was to evaluate which of these (often simplified) methods could potentially be used for clinical response monitoring studies in breast cancer. Prior to chemotherapy, dynamic [18F]FDG scans were performed in 20 women with locally advanced (n=10) or metastasised (n=10) breast cancer. Additional PET scans were acquired after 8 days (n=8), and after one, three and six courses of chemotherapy (n=18, 10 and 6, respectively). Non-linear regression (NLR) with the standard two tissue compartment model was used as the gold standard for measurement of [18F]FDG uptake and was compared with the following methods: Patlak graphical analysis, simplified kinetic method (SKM), SUV-based net influx constant ("Sadato" method), standard uptake value [normalised for weight, lean body mass (LBM) and body surface area (BSA), with and without corrections for glucose (g)], tumour to non-tumour ratio (TNT), 6P model and total lesion evaluation (TLE). Correlation coefficients between each analytical method and NLR were calculated using multilevel analysis. In addition, for the most promising methods (Patlak, SKM, SUVLBMg and SUVBSAg) it was explored whether correlation with NLR changed with different time points after the start of therapy. Three methods showed excellent correlation (r>0.95) with NLR for the baseline scan: Patlak10–60 and Patlak10–45 (r=0.98 and 0.97, respectively), SKM40–60 (r=0.96) and SUVLBMg (r=0.96). Good correlation was found between NLR and SUV-based net influx constant, TLE and SUVBSAg (0.90<r<0.95). The 6P model and TNT had the lowest correlation (r≤0.84). SUV was least accurate in predicting changes in [18F]FDG uptake over time during therapy. For all methods, correlation with NLR was significantly lower for bone metastases than for other (primary or metastatic) tumour lesions (P<0.05). In conclusion, three methods with different degrees of complexity appear to be promising alternatives to NLR for measuring glucose metabolism in breast cancer: Patlak, SKM and SUV (normalised for LBM and with a correction for plasma glucose).

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Authors and Affiliations

  1. Clinical PET Centre, VU University Medical Centre, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands

    Nanda C. Krak, Otto S. Hoekstra & Adriaan A. Lammertsma

  2. Department of Clinical Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam, The Netherlands

    Otto S. Hoekstra & Jos W. R. Twisk

  3. Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands

    Elsken van der Wall

  4. Amstelveen Hospital, Amstelveen, The Netherlands

    Jacobus J. M. van der Hoeven

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  1. Nanda C. Krak
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Correspondence to Adriaan A. Lammertsma.

Appendix

Appendix

Patlak graphical analysis (Patlak)

This method [28] assumes unidirectional uptake of [18F]FDG (i.e. k 4=0), with irreversible trapping in tissue as [18F]FDG-6-PO4. The Patlak method was applied to several data intervals: 10–60, 10–45, 10–30, 20–60 and 30–60 min post injection. The lumped constant LC was assumed to be unity.

Standard uptake value (SUV)

The SUV is the ratio of tissue concentration and injected activity [25, 26, 27]. It is a semi-quantitative method, which does not take FDG kinetics into account. In the present study calculations were performed using both 40–60 and 50–60 min acquisition intervals. SUV was normalised to weight (SUVW), lean body mass (SUVLBM) [56] and body surface area (SUVBSA) [45] and calculated with and without plasma glucose (g) correction. BSA=0.007184×weight0.425×height0.725 and LBM=45.5+0.91(height−152).

The simplified kinetic method (SKM)

The SKM [29] is similar to the SUV (static image with both 40–60 and 50–60 min acquisition intervals), except that a correction is made for the actual plasma clearance of [18F]FDG. In the present analysis, venous blood samples taken at 35, 45 and 55 min post injection were used to incorporate the individual plasma clearance.

The SUV-based net influx constant ("Sadato" method)

In this method [30] the net influx constant (K i) is derived from SUV and a population-based plasma input function. This analysis was performed for the 40–60 min acquisition interval and corrections for both body weight and body surface area were applied.

Two-ROI, 6P method (6P model)

The 6P model [33] combines the kinetics in two ROIs (tumour and non-tumour reference regions) using six parameters (four rate constants, tumour and vascular fractions). Like NLR, it requires full dynamic scanning, but it accounts for the admixture of non-tumour components in a tumour. In this paper either small (6P modelsmall) or large (6P modellarge) reference regions in the normal breast were used.

Tumour to non-tumour ratio (TNT)

The TNT is a simple semi-quantitative index that only requires a static image and no scanner calibration. In this study, TNT was measured using 40–60 and 50–60 min acquisition intervals. As non-tumour regions, the same ROIs were used as for the 6P model.

Total lesion evaluation (TLE)

Correlation coefficient constrained parametric images (10–60 min acquisition interval) were obtained from the Patlak parametric images by setting all pixels with a linear correlation coefficient below a certain threshold to 0 [32]. Correlation coefficient thresholds of 0.5, 0.6, 0.7, 0.8 and 0.9 were used. All images containing a tumour lesion were summed, a single ROI was defined covering the entire lesion in this summed image, and subsequently the total lesion metabolic index was calculated.

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Krak, N.C., van der Hoeven, J.J.M., Hoekstra, O.S. et al. Measuring [18F]FDG uptake in breast cancer during chemotherapy: comparison of analytical methods. Eur J Nucl Med Mol Imaging 30, 674–681 (2003). https://doi.org/10.1007/s00259-003-1127-z

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