Experimental PET imaging
The limitation of PET imaging for biological adaptive-IMRT assessed in animal models

https://doi.org/10.1016/j.radonc.2008.11.014Get rights and content

Abstract

Purpose

Biological image-guided radiotherapy aims at specifically irradiating biologically relevant sub-volumes within the tumor, as determined for instance by PET imaging. This approach requires that PET imaging be sensitive and specific enough to image various biological pathways of interest, e.g. tumor metabolism, proliferation and hypoxia. In this framework, a validation of PET imaging used for adaptive radiotherapy was undertaken in animal models by comparing small-animal PET images (2.7 mm resolution) with autoradiography (AR) (100 μm resolution) in various tumors under various physiological situations.

Methods

A specific template for tumor-bearing mouse imaging has been designed (Christian, R&O, 2008). It allows for the registration between MRI images (Biospec, Bruker), FDG–PET images (Mosaic, Philips) and AR (FLA-5100, Fujifilm). After registration, the tumors on the PET and AR images were segmented using a threshold-based method. The thresholds were selected to obtain absolute equal volumes in the PET and AR images. Matching indexes were then calculated between the various volumes. The entire imaging process was performed for FSAII tumors (n = 5), SCCVII (n = 5) and irradiated (35 Gy) FSAII tumors (n = 5).

Results

In regions with high FDG activity delineated using high value thresholds, low matching values of 39% ± 11% (mean ± SD) were observed between the volumes delineated on the PET images and those delineated on AR. The matching values progressively increased when considering larger volumes obtained with lower thresholds. These findings were independent of tumor type, tumor metabolism or tumor size. The relationship between the matching values and the percentage of overall tumor volume was fitted through a power regression (r = 0.93). As shown by simulations, the matching improved with higher PET resolution. The results can be extrapolated to human tumors imaged with a whole-body PET system.

Conclusion

Discrepancies were found between the PET images and the underlying microscopic reality represented by AR images. These differences, attributed to the finite resolution of PET, were important when considering small and highly active regions of the tumors. Dose painting based on PET images should therefore be carefully considered and should take these limitations into account.

Section snippets

Animal and tumor model

Seven- to 12-week-old male C3H/HeOuJIco (IFFA Credo Belgium) mice were used for this study. Animals were maintained in a facility approved by the Belgian Ministry of Agriculture in accordance with current regulations and standards. They were housed 4–5 per cage and fed ad libitum. FSA II fibrosarcoma or SCCVII squamous cell carcinoma syngeneic to C3Hf/Kam mice was generated in the right thigh. These tumors were kindly provided by Dr. L. Milas from the University of Texas, M.D. Anderson Cancer

Tumor models

For the 15 mice used in these experiments, the mean tumor volume assessed on MRI images reached 1.65 ± 0.49 ml. In the three different groups, the mean volumes were 1.50 ± 0.49, 1.72 ± 0.39 and 1.86 ± 0.62 ml for the FSAII tumors, SCCVII tumors and FSAII + RX tumors, respectively. Tumor volume was not significantly different between the groups (one-way ANOVA: p = 0.53). The smaller tumor reached 0.92 ml (FSAII group) and the larger tumor reached 2.70 ml (FSAII + RX group).

Voxel-by-voxel analysis

After registration, the tumor was

Discussion

Our study demonstrated that sub-volumes of mouse tumors with high FDG–PET activity, which likely represent the regions where radiation dose might be escalated, poorly matched with the underlying reality assessed by autoradiography (Fig. 3). It was also shown that these results could be extrapolated to human tumors imaged with a whole-body PET camera. Last, it was shown that the use of PET camera with a higher resolution would definitely improve the whole scenario (Fig. 4).

We established that

Acknowledgments

Nicolas Christian is a research fellow of the “Fonds pour la formation à la Recherche dans l’Industrie et l’Agriculture (F.R.I.A.)” of Belgium. The project was supported by a grant from the “Fonds Joseph Maisin”, Brussels, Belgium, by the European Commission’s Sixth Framework Programme funding (Contract N°. LSHC-CT-2004-505785), and by a program project from the “Institut National du Cancer” of France (Project INCa N° RS 020).

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