Simplified quantification of FDG metabolism in tumors using the autoradiographic method is less dependent on the acquisition time than SUV,☆☆

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Abstract

The standard uptake value (SUV) is the most often used semi-quantitative measure of 18F-fluorodeoxyglucose (FDG) uptake. We tested the hypothesis that the autoradiographic method with a population-based input curve yields an approximation of FDG metabolism represented by the flux value Ki, which is less dependent on the acquisition time point than SUV.

Methods

We analyzed 20 patients with chest tumors (16 males, age 65±10 years). After injection of 350 MBq FDG using the INTEGO PET infusion system, a series of 35 scans of 10- to 300-s duration were acquired until 45 min. FDG flux was calculated using the Patlak method (Kipatlak) and also quantified with the autoradiographic method using the last acquisition only and the individual image-derived input function (Kiautoreal), as well as with a population-based input function (Kiautonorm). In a simulation study, the time courses of tumor SUV, tumor-to-blood ratio and tumor Ki values were calculated from 30 to 90 min.

Results

The FDG flux values (Ki) of the different tumors, obtained with the autoradiographic methods and the Patlak method, showed a high correlation. The simulation study showed a 16.8±3.3% increase in the SUV values from 50 to 70 min, but only a 1.3±2.8% change in the Ki values calculated with the autoradiographic method.

Conclusion

Compared to the SUV, the autoradiographic Ki values are advantageous for various reasons. First, they are much less dependent on the time of acquisition than the SUV. Second, their calculation does not require the knowledge of the body weight or the injected activity. Furthermore, the values are comparable to the ones obtained with the widely accepted Patlak method. The method can be easily implemented in a clinical setting, as it uses only one static scan.

Introduction

The increasing use of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oncology significantly improved patient management [1]. Especially for primary staging of cancers and in treatment evaluation, FDG increased the sensitivity and specificity of morphologic imaging [2], [3], [4], [5]. Imaging typically consists of a single whole-body scan acquired at around 45–60 min following the injection of FDG [6], [7]. For reporting findings, the FDG tissue uptake (kBq/ml) is usually divided by the injected dose (MBq) and multiplied by the lean body weight (kg) to obtain the standard uptake value (SUV, g/ml) [8]. SUV values are critically dependent on the time of acquisition and on an accurate measurement of the lean body mass [9], [10]. Despite its known limitations, SUV is the most often clinically used quantification of tumor metabolism due to the straightforward calculation [10], [11]. There exist more accurate methods for the quantification of FDG metabolism as has been extensively shown in the past [10], [12], [13], [14]. One well-established method based on dynamic imaging is the graphical method according to Patlak et al. [15]. This method requires the time course of the tracer activity in the target tissue as well as in arterial blood plasma (input function) from the time of FDG injection until the end of the study. Hunter et al. [16] investigated several simplified FDG quantification methods for non–small cell lung cancer. Regarding the use of image-derived input functions, they found that the replacement of the individual input function by a population-averaged function resulted in a highly correlated Patlak outcome, which, however, showed a consistent underestimation. De Geus-Oei et al. [17] showed that the Patlak method can also be used in combination with the whole-blood activity curve derived from the cavity of the left ventricle instead of arterial plasma samples for the therapy monitoring of tumor patients. As another simplified measure, Hunter et al. [16] studied the use of the tracer retention, which is the tissue activity divided by the integral of the blood activity. For tumor tissue, tracer retention is highly correlated with the Patlak slope even when the arterial input curve was replaced by a population-based input function derived by a tri-exponential function fitted to the data of 26 studies of non–small cell lung cancer patients.

Another simplified approach for the quantification of FDG is the autoradiographic method introduced by Sokoloff et al. [18] for rats and further adjusted for human brain applications by Huang et al. [19]. For this method, the tissue activity at one late time point is sufficient, whereas the full input function until the end of PET scanning is required. The current study investigated the suitability of the autoradiographic method to yield accurate FDG flux values, using a single scan and a calibrated population-based input function. For this approach to be viable, the input functions across patients must be sufficiently similar in shape. This similarity can most likely be improved by using an automatic injection device such as the INTEGO PET infusion system (Medrad, Pittsburgh, PA, USA) which ensures a consistent tracer application. Vriens et al. [20] showed that a triexponential fit to the decay curve calibrated with one arterial blood sample yields an area under the input curve very similar to the dynamically sampled input curve.

Quantification methods based on a single image acquisition are dependent on the time after injection when the image is acquired. Therefore, the sensitivity of the autoradiographic method regarding the acquisition time was assessed in a simulation study and compared with that of conventional SUV values, as well as the tumor-to-blood pool ratio.

Section snippets

Patients

Inclusion criterion was that the lesion was close enough to the heart for the PET field of view (14.6 cm) to cover both tumor and left ventricle.

PET imaging

With the injection of 320 to 360 MBq FDG over 30 s using the INTEGO PET infusion system (Medrad), a dynamic PET scan of 35 frames was initiated (12×10, 16×30, 7×300 s, 45-min duration) on a whole-body PET/CT scanner. The axial field of view was positioned such that it enclosed the tumor as well as the left ventricle. After completion of the dynamic

Patient characteristics

Twenty patients (4 females, 16 males, mean age 65.4±10.2 years; body mass index 32.5±4.7 kg/m2) referred to FDG PET/CT for the assessment of known or suspected thoracic tumors were prospectively selected, if the tumor was in the same field of view as the left ventricle to allow dynamic imaging. In 12 patients, histopathology revealed small cell lung cancer; in two patients, esophageal cancer; in three patients, pulmonary adenocarcinoma; and in one patient, sarcoma metastasis, a neuroendocrine

Discussion

FDG PET/CT has become a standard procedure in the evaluation of cancer patients. It is used in the initial staging of certain malignancies and increasingly in treatment evaluation. Treatment response can be classified according to guidelines, for instance, the recently published PERCIST [21]. These guidelines use SUV values as their basis. The advantage of SUV is that it can be easily calculated, but it is hampered by several drawbacks. One is its critical dependence on the time point of the

Conclusion

Compared to the SUV, the autoradiographic Ki values are advantageous for various reasons. First, they are much less dependent on the time of acquisition than the SUV. Second, their calculation does not require the knowledge of the body weight or the injected activity. Furthermore, the values are comparable to the ones obtained with the standard Patlak method. The method can be easily implemented in a clinical setting, as it uses only one static scan.

Acknowledgments

The authors would like to thank the PET technicians for the help in the data acquisition.

References (25)

  • N. Sadato et al.

    Non-invasive estimation of the net influx constant using the standardized uptake value for quantification of FDG uptake of tumours

    Eur J Nucl Med

    (1998)
  • M. Houseni et al.

    Prognostic implication of dual-phase PET in adenocarcinoma of the lung

    J Nucl Med

    (2010)
  • Cited by (0)

    The study was financially supported by Medrad, Pittsburgh, PA, USA.

    ☆☆

    Conflict of interest: Alfred Buck is receiving royalties from Medrad. The rest of the authors declare no other conflicts of interest.

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